MLH1_HUMAN
ID MLH1_HUMAN Reviewed; 756 AA.
AC P40692; B4DI13; B4DQ11; E9PCU2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=DNA mismatch repair protein Mlh1;
DE AltName: Full=MutL protein homolog 1;
GN Name=MLH1; Synonyms=COCA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8145827; DOI=10.1038/368258a0;
RA Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G.,
RA Lescoe M.K., Kane M.F., Earibino C., Lipford J., Lindblom A.,
RA Tannergaard P., Bollag R.J., Godwin A.R., Ward D.C., Nordenskjoeld M.,
RA Fishel R., Kolodner R.D., Liskay R.M.;
RT "Mutation in the DNA mismatch repair gene homologue hMLH1 is associated
RT with hereditary non-polyposis colon cancer.";
RL Nature 368:258-261(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Gall bladder;
RX PubMed=8128251; DOI=10.1126/science.8128251;
RA Papadopoulos N., Nicolaides N.C., Wei Y.-F., Ruben S.M., Carter K.C.,
RA Rosen C.A., Haseltine W.A., Fleischmann R.D., Fraser C.M., Adams M.D.,
RA Venter J.C., Hamilton S.R., Petersen G.M., Watson P., Lynch H.T.,
RA Peltomaeki P., Mecklin J.-P., de la Chapelle A., Kinzler K.W.,
RA Vogelstein B.;
RT "Mutation of a mutL homolog in hereditary colon cancer.";
RL Science 263:1625-1629(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7812952;
RA Kolodner R.D., Hall N.R., Lipford J.R., Kane M.F., Morrison P., Finan P.J.,
RA Burn J., Chapman P., Earabino C., Merchant E., Bishop D.T.;
RT "Structure of the human MLH1 locus and analysis of a large hereditary
RT nonpolyposis colorectal carcinoma kindred for mlh1 mutations.";
RL Cancer Res. 55:242-248(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HNPCC2 LEU-542; PRO-574;
RP VAL-582 AND THR-618.
RX PubMed=7757073; DOI=10.1093/hmg/4.2.237;
RA Han H.-J., Maruyama M., Baba S., Park J.-G., Nakamura Y.;
RT "Genomic structure of human mismatch repair gene, hMLH1, and its mutation
RT analysis in patients with hereditary non-polyposis colorectal cancer
RT (HNPCC).";
RL Hum. Mol. Genet. 4:237-242(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-32; MET-213 AND
RP VAL-219.
RG NIEHS SNPs program;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, Corpus callosum, Kidney, and Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP IDENTIFICATION OF MLH1 AS MEMBER OF BASC.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [11]
RP INTERACTION WITH MBD4.
RX PubMed=10097147; DOI=10.1073/pnas.96.7.3969;
RA Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T.,
RA Matsumoto Y., Golemis E.A., Genuardi M., Neri G.;
RT "MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA
RT mismatch repair protein MLH1.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999).
RN [12]
RP INTERACTION WITH EXO1 AND PMS2, CHARACTERIZATION OF VARIANTS HNPCC2
RP PRO-574; LYS-616 DEL; LEU-659 AND THR-681, AND CHARACTERIZATION OF VARIANT
RP MMRCS1 LYS-616 DEL.
RX PubMed=11427529; DOI=10.1074/jbc.m102670200;
RA Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.;
RT "The interaction of DNA mismatch repair proteins with human exonuclease
RT I.";
RL J. Biol. Chem. 276:33011-33018(2001).
RN [13]
RP INTERACTION WITH EXO1, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP VARIANT MET-117.
RX PubMed=11429708; DOI=10.1038/sj.onc.1204467;
RA Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C.,
RA Rasmussen L.J.;
RT "HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence
RT assembly of hMutLalpha and hMLH1-hEXO1 complexes.";
RL Oncogene 20:3590-3595(2001).
RN [14]
RP INTERACTION WITH EXO1.
RX PubMed=12414623;
RA Sun X., Zheng L., Shen B.;
RT "Functional alterations of human exonuclease 1 mutants identified in
RT atypical hereditary nonpolyposis colorectal cancer syndrome.";
RL Cancer Res. 62:6026-6030(2002).
RN [15]
RP INTERACTION WITH EXO1, AND SUBCELLULAR LOCATION.
RX PubMed=14676842; DOI=10.1038/sj.onc.1207265;
RA Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J.;
RT "Characterization of human exonuclease 1 in complex with mismatch repair
RT proteins, subcellular localization and association with PCNA.";
RL Oncogene 23:1457-1468(2004).
RN [16]
RP INVOLVEMENT IN MRTES.
RX PubMed=8751876;
RA Bapat B., Xia L., Madlensky L., Mitri A., Tonin P., Narod S.A.,
RA Gallinger S.;
RT "The genetic basis of Muir-Torre syndrome includes the hMLH1 locus.";
RL Am. J. Hum. Genet. 59:736-739(1996).
RN [17]
RP FUNCTION.
RX PubMed=16873062; DOI=10.1016/j.cell.2006.05.039;
RA Kadyrov F.A., Dzantiev L., Constantin N., Modrich P.;
RT "Endonucleolytic function of MutLalpha in human mismatch repair.";
RL Cell 126:297-308(2006).
RN [18]
RP FUNCTION.
RX PubMed=18206974; DOI=10.1016/j.molcel.2007.10.030;
RA Sacho E.J., Kadyrov F.A., Modrich P., Kunkel T.A., Erie D.A.;
RT "Direct visualization of asymmetric adenine nucleotide-induced
RT conformational changes in MutL alpha.";
RL Mol. Cell 29:112-121(2008).
RN [19]
RP REVIEW.
RX PubMed=16188885; DOI=10.1074/jbc.m509701200;
RA Constantin N., Dzantiev L., Kadyrov F.A., Modrich P.;
RT "Human mismatch repair: reconstitution of a nick-directed bidirectional
RT reaction.";
RL J. Biol. Chem. 280:39752-39761(2005).
RN [20]
RP REVIEW.
RX PubMed=16873053; DOI=10.1016/j.cell.2006.07.003;
RA Jiricny J.;
RT "MutLalpha: at the cutting edge of mismatch repair.";
RL Cell 126:239-241(2006).
RN [21]
RP REVIEW.
RX PubMed=18157157; DOI=10.1038/cr.2007.115;
RA Li G.M.;
RT "Mechanisms and functions of DNA mismatch repair.";
RL Cell Res. 18:85-98(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [24]
RP INTERACTION WITH MTMR15.
RX PubMed=20603073; DOI=10.1016/j.molcel.2010.06.023;
RA Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P.,
RA Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P.,
RA Elledge S.J.;
RT "A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease
RT necessary for DNA interstrand crosslink repair.";
RL Mol. Cell 39:36-47(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP IDENTIFICATION IN THE MMR COMPLEX, INTERACTION WITH MCM9 AND MCM8, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26300262; DOI=10.1016/j.molcel.2015.07.010;
RA Traver S., Coulombe P., Peiffer I., Hutchins J.R., Kitzmann M.,
RA Latreille D., Mechali M.;
RT "MCM9 Is Required for Mammalian DNA Mismatch Repair.";
RL Mol. Cell 59:831-839(2015).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 486-751.
RA Dombrovsky L., Dong A., Wernimont A., Loppnau P., Bountra C., Weigelt J.,
RA Arrowsmith C.H., Edwards A.M., Min J., Wu H.;
RT "Crystal structure of MutL protein homolog 1 isoform 1.";
RL Submitted (MAR-2011) to the PDB data bank.
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 3-196 IN COMPLEX WITH ADP AND
RP MAGNESIUM IONS.
RX PubMed=26249686; DOI=10.1107/s2053230x15010183;
RA Wu H., Zeng H., Lam R., Tempel W., Kerr I.D., Min J.;
RT "Structure of the human MLH1 N-terminus: implications for predisposition to
RT Lynch syndrome.";
RL Acta Crystallogr. F 71:981-985(2015).
RN [33]
RP CHARACTERIZATION OF VARIANTS HNPCC2 CYS-31; LYS-37; HIS-38; LYS-38; PHE-44;
RP ARG-67; PRO-109; PRO-111; MET-117; CYS-265; SER-265; GLN-443; PRO-550;
RP GLY-578; PHE-582; ASP-589; ALA-618; CYS-646; LEU-648; LEU-654 AND PRO-659,
RP CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716,
RP AND FUNCTION.
RX PubMed=20020535; DOI=10.1002/humu.21180;
RA Drost M., Zonneveld J.B., van Dijk L., Morreau H., Tops C.M., Vasen H.F.,
RA Wijnen J.T., de Wind N.;
RT "A cell-free assay for the functional analysis of variants of the mismatch
RT repair protein MLH1.";
RL Hum. Mutat. 31:247-253(2010).
RN [34]
RP CHARACTERIZATION OF VARIANTS HNPCC2 LEU-28; SER-29; 45-THR--ILE-47 DELINS
RP CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107;
RP ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; GLN-443; ALA-460; PRO-550;
RP 578-GLU--GLU-632 DEL; ASP-589; VAL-612 DEL; LYS-616 DEL; ALA-618; THR-618;
RP 633-GLU--GLU-663 DEL; CYS-646; LEU-648; SER-648; LEU-654; GLN-659; PRO-659;
RP THR-681 AND TRP-687, CHARACTERIZATION OF VARIANTS GLY-93; MET-213; VAL-219
RP AND MET-716, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=21120944; DOI=10.1002/humu.21409;
RA Kansikas M., Kariola R., Nystroem M.;
RT "Verification of the three-step model in assessing the pathogenicity of
RT mismatch repair gene variants.";
RL Hum. Mutat. 32:107-115(2011).
RN [35]
RP VARIANT MMRCS1 LYS-616 DEL.
RX PubMed=7661930; DOI=10.1056/nejm199503303321302;
RA Hamilton S.R., Liu B., Parsons R.E., Papadopoulos N., Jen J., Powell S.M.,
RA Krush A.J., Berk T., Cohen Z., Tetu B., Burger P.C., Wood P.A., Taqi F.,
RA Booker S.V., Petersen G.M., Offerhaus G.J.A., Tersmette A.C.,
RA Giardiello F.M., Vogelstein B., Kinzler K.W.;
RT "The molecular basis of Turcot's syndrome.";
RL N. Engl. J. Med. 332:839-847(1995).
RN [36]
RP VARIANT HNPCC2 LYS-616 DEL.
RX PubMed=8571956;
RA Wijnen J., Khan P.M., Vasen H., Menko F., van der Klift H.,
RA van den Broek M., van Leeuwen-Cornelisse I., Nagengast F.,
RA Meijers-Heijboer E.J., Lindhout D., Griffioen G., Cats A., Kleibeuker J.,
RA Varesco L., Bertario L., Bisgaard M.-L., Mohr J., Kolodner R.D., Fodde R.;
RT "Majority of hMLH1 mutations responsible for hereditary nonpolyposis
RT colorectal cancer cluster at the exonic region 15-16.";
RL Am. J. Hum. Genet. 58:300-307(1996).
RN [37]
RP VARIANTS HNPCC2 MET-117 AND LEU-226.
RX PubMed=8566964; DOI=10.1007/bf02265276;
RA Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P.,
RA Buerstedde J.-M.;
RT "CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC
RT mutations.";
RL Hum. Genet. 97:251-255(1996).
RN [38]
RP VARIANTS HNPCC2 LYS-616 DEL AND THR-618, AND VARIANT CRC THR-492.
RX PubMed=8872463; DOI=10.1093/hmg/5.9.1245;
RA Moslein G., Tester D.J., Lindor N.M., Honchel R., Cunningham J.M.,
RA French A.J., Halling K.C., Schwab M., Goretzki P., Thibodeau S.N.;
RT "Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in
RT patients with sporadic, familial and hereditary colorectal cancer.";
RL Hum. Mol. Genet. 5:1245-1252(1996).
RN [39]
RP VARIANTS HNPCC2 CYS-217; LEU-542; PRO-549 AND PRO-574.
RX PubMed=8797773; DOI=10.1093/jnci/88.18.1317;
RA Han H.-J., Yuan Y., Ku J.-L., Oh J.-H., Won Y.-J., Kang K.J., Kim K.Y.,
RA Kim S., Kim C.Y., Kim J.-P., Oh N.-G., Lee K.H., Choe K.J., Nakamura Y.,
RA Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary
RT nonpolyposis colorectal cancer.";
RL J. Natl. Cancer Inst. 88:1317-1319(1996).
RN [40]
RP VARIANTS LEU-ASN-HIS-37 INS AND ASP-384.
RX PubMed=8609062; DOI=10.1111/j.1349-7006.1996.tb03151.x;
RA Kobayashi K., Matsushima M., Koi S., Saito H., Sagae S., Kudo R.,
RA Nakamura Y.;
RT "Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic
RT endometrial carcinomas with microsatellite instability.";
RL Jpn. J. Cancer Res. 87:141-145(1996).
RN [41]
RP VARIANTS HNPCC2 LYS-62; SER-64; LYS-616 DEL; ALA-618 AND PRO-659,
RP CHARACTERIZATION OF VARIANT HNPCC2 LYS-62, AND FUNCTION.
RX PubMed=9311737; DOI=10.1086/514847;
RA Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A.,
RA van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P., Fodde R.;
RT "Hereditary nonpolyposis colorectal cancer families not complying with the
RT Amsterdam criteria show extremely low frequency of mismatch-repair-gene
RT mutations.";
RL Am. J. Hum. Genet. 61:329-335(1997).
RN [42]
RP VARIANT HNPCC2 LYS-616 DEL, AND VARIANT HIS-265.
RX PubMed=8993976;
RX DOI=10.1002/(sici)1098-2264(199701)18:1<8::aid-gcc2>3.0.co;2-7;
RA Viel A., Genuardi M., Capozzi E., Leonardi F., Bellacosa A.,
RA Paravatou-Petsotas M., Pomponi M.G., Fornasarig M., Percesepe A.,
RA Roncucci L., Tamassia M.G., Benatti P., Ponz de Leon M., Valenti A.,
RA Covino M., Anti M., Foletto M., Boiocchi M., Neri G.;
RT "Characterization of MSH2 and MLH1 mutations in Italian families with
RT hereditary nonpolyposis colorectal cancer.";
RL Genes Chromosomes Cancer 18:8-18(1997).
RN [43]
RP VARIANTS CRC GLU-54; VAL-244 AND GLN-325, AND VARIANTS VAL-219 AND ASN-406.
RX PubMed=9087566;
RX DOI=10.1002/(sici)1098-2264(199704)18:4<269::aid-gcc4>3.0.co;2-z;
RA Wu Y., Nystroem-Lahti M., Osinga J., Looman M.W.G., Peltomaeki P.,
RA Aaltonen L.A., de la Chapelle A., Hofstra R.M.W., Buys C.H.C.M.;
RT "MSH2 and MLH1 mutations in sporadic replication error-positive colorectal
RT carcinoma as assessed by two-dimensional DNA electrophoresis.";
RL Genes Chromosomes Cancer 18:269-278(1997).
RN [44]
RP VARIANTS HNPCC2 PRO-128 AND ASP-244, AND VARIANT VAL-219.
RX PubMed=9218993;
RX DOI=10.1002/(sici)1098-2264(199707)19:3<135::aid-gcc1>3.0.co;2-z;
RA Pensotti V., Radice P., Presciuttini S., Calistri D., Gazzoli I.,
RA Grimalt Perez A.P., Mondini P., Buonsanti G., Sala P., Rossetti C.,
RA Ranzani G.N., Bertario L., Pierotti M.A.;
RT "Mean age of tumor onset in hereditary nonpolyposis colorectal cancer
RT (HNPCC) families correlates with the presence of mutations in DNA mismatch
RT repair genes.";
RL Genes Chromosomes Cancer 19:135-142(1997).
RN [45]
RP VARIANT HNPCC2 626-SER-THR-627.
RX PubMed=9048925; DOI=10.1007/s004390050343;
RA Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V.,
RA Harocopos C.J., Bodmer W.F.;
RT "Use of SSCP analysis to identify germline mutations in HNPCC families
RT fulfilling the Amsterdam criteria.";
RL Hum. Genet. 99:219-224(1997).
RN [46]
RP VARIANT HNPCC2 PRO-329.
RX PubMed=9272156; DOI=10.1007/s004390050517;
RA Wang Y., Friedl W., Lamberti C., Ruelfs C., Kruse R., Propping P.;
RT "Hereditary nonpolyposis colorectal cancer: causative role of a germline
RT missense mutation in the hMLH1 gene confirmed by the independent occurrence
RT of the same somatic mutation in tumour tissue.";
RL Hum. Genet. 100:362-364(1997).
RN [47]
RP VARIANT HNPCC2 ARG-67, AND VARIANT VAL-219.
RX PubMed=9067757;
RX DOI=10.1002/(sici)1098-1004(1997)9:2<164::aid-humu9>3.0.co;2-9;
RA Sasaki S., Tokino T., Miyatsu T., Muto T., Nakamura Y.;
RT "Mutational analysis of the hMLH1 gene using an automated two-dimensional
RT DNA typing system.";
RL Hum. Mutat. 9:164-171(1997).
RN [48]
RP REVIEW ON VARIANTS.
RX PubMed=9259192;
RX DOI=10.1002/(sici)1098-1004(1997)10:2<89::aid-humu1>3.0.co;2-h;
RA Papadopoulos N., Lindblom A.;
RT "Molecular basis of HNPCC: mutations of MMR genes.";
RL Hum. Mutat. 10:89-99(1997).
RN [49]
RP VARIANT HNPCC2 LEU-28.
RX PubMed=9298827;
RX DOI=10.1002/(sici)1098-1004(1997)10:3<241::aid-humu12>3.0.co;2-#;
RA Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R., Propping P.,
RA Friedl W.;
RT "Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline
RT mutations in hMSH2 or hMLH1 genes.";
RL Hum. Mutat. 10:241-244(1997).
RN [50]
RP VARIANTS HNPCC2 GLY-182; THR-295 AND THR-551.
RX PubMed=9399661;
RX DOI=10.1002/(sici)1097-0215(19971210)73:6<831::aid-ijc11>3.0.co;2-7;
RA Wang Q., Desseigne F., Lasset C., Saurin J.-C., Navarro C., Yagci T.,
RA Keser I., Bagci H., Luleci G., Gelen T., Chayvialle J.-A., Puisieux A.,
RA Ozturk M.;
RT "Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families.";
RL Int. J. Cancer 73:831-836(1997).
RN [51]
RP VARIANT CRC TYR-77, AND VARIANT VAL-219.
RX PubMed=9032648; DOI=10.1136/jmg.34.1.39;
RA Tomlinson I.P.M., Beck N.E., Homfray T., Harocopos C.J., Bodmer W.F.;
RT "Germline HNPCC gene variants have little influence on the risk for
RT sporadic colorectal cancer.";
RL J. Med. Genet. 34:39-42(1997).
RN [52]
RP VARIANTS HNPCC2 PHE-44 AND THR-441.
RX PubMed=9326924; DOI=10.1038/ng1097-135;
RA Hackman P., Tannergaerd P., Osei-Mensa S., Chen J., Kane M.F.,
RA Kolodner R.D., Lambert B., Hellgren D., Lindblom A.;
RT "A human compound heterozygote for two MLH1 missense mutations.";
RL Nat. Genet. 17:135-136(1997).
RN [53]
RP VARIANTS HNPCC2, AND VARIANTS.
RX PubMed=9718327; DOI=10.1086/301996;
RA Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D.,
RA Robbins D.J., Dunlop M.G.;
RT "Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and
RT controls.";
RL Am. J. Hum. Genet. 63:749-759(1998).
RN [54]
RP VARIANT CRC GLY-268.
RX PubMed=9611074; DOI=10.1111/j.1399-0004.1998.tb02660.x;
RA Liu T., Wahlberg S., Rubio C., Holmberg E., Groenberg H., Lindblom A.;
RT "DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in
RT 34 Swedish families with colorectal cancer.";
RL Clin. Genet. 53:131-135(1998).
RN [55]
RP VARIANT HNPCC2 CYS-217.
RX PubMed=9559627; DOI=10.1007/bf02235756;
RA Yuan Y., Han H.-J., Zheng S., Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in patients with suspected
RT hereditary nonpolyposis colorectal cancer and sporadic early-onset
RT colorectal cancer.";
RL Dis. Colon Rectum 41:434-440(1998).
RN [56]
RP VARIANT ASP-384, AND ASSOCIATION WITH HNPCC.
RX PubMed=9526167; DOI=10.1159/000022786;
RA Wang Y., Friedl W., Lamberti C., Noethen M.M., Kruse R., Propping P.;
RT "A novel missense mutation in the DNA mismatch repair gene hMLH1 present
RT among East Asians but not among Europeans.";
RL Hum. Hered. 48:87-91(1998).
RN [57]
RP VARIANT HNPCC2 LYS-69.
RX PubMed=10627141;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<73::aid-humu20>3.0.co;2-f;
RA Herfarth K.K.-F., Ogunbiyi O.A., Moley J.F., Kodner I.J., Wells S.A. Jr.,
RA Goodfellow P.J.;
RT "Four new mutations in the DNA mismatch repair gene MLH1 in colorectal
RT cancers with microsatellite instability.";
RL Hum. Mutat. 12:73-73(1998).
RN [58]
RP VARIANTS HNPCC2 ARG-77 AND PRO-193.
RX PubMed=10660333;
RA Panariello L., Scarano M.I., de Rosa M., Capasso L., Renda A., Riegler G.,
RA Rossi G.B., Salvatore F., Izzo P.;
RT "hMLH1 mutations in hereditary nonpolyposis colorectal cancer kindreds.";
RL Hum. Mutat. 12:216-217(1998).
RN [59]
RP VARIANT GLY-93.
RX PubMed=10671064;
RX DOI=10.1002/(sici)1098-1004(1998)12:6<433::aid-humu13>3.0.co;2-j;
RA Quaresima B., Grandinetti C., Baudi F., Tassone P., Barbieri V.,
RA Conforti S., Avvedimento E.V., Costanzo F., Venuta S.;
RT "Hereditary nonpolyposis colorectal cancer: identification of novel
RT germline mutations in two kindreds not fulfilling the Amsterdam criteria.";
RL Hum. Mutat. 12:433-433(1998).
RN [60]
RP VARIANTS HNPCC2 ARG-67; ILE-262 DEL; THR-551 AND PHE-565, AND VARIANTS
RP VAL-219 AND MET-716.
RX PubMed=9833759;
RX DOI=10.1002/(sici)1097-0215(19981209)78:6<680::aid-ijc3>3.0.co;2-u;
RA Hutter P., Couturier A., Membrez V., Joris F., Sappino A.-P.,
RA Chappuis P.O.;
RT "Excess of hMLH1 germline mutations in Swiss families with hereditary non-
RT polyposis colorectal cancer.";
RL Int. J. Cancer 78:680-684(1998).
RN [61]
RP VARIANTS HNPCC2 ARG-67; ARG-117 AND GLU-485, AND VARIANT VAL-219.
RX PubMed=10375096;
RX DOI=10.1002/(sici)1097-0142(19990615)85:12<2512::aid-cncr4>3.0.co;2-g;
RA Heinimann K., Scott R.J., Buerstedde J.-M., Weber W., Siebold K.,
RA Attenhofer M., Mueller H., Dobbie Z.;
RT "Influence of selection criteria on mutation detection in patients with
RT hereditary nonpolyposis colorectal cancer.";
RL Cancer 85:2512-2518(1999).
RN [62]
RP VARIANT HNPCC2 TRP-67.
RX PubMed=9927034;
RA Wang Q., Lasset C., Desseigne F., Frappaz D., Bergeron C., Navarro C.,
RA Ruano E., Puisieux A.;
RT "Neurofibromatosis and early onset of cancers in hMLH1-deficient
RT children.";
RL Cancer Res. 59:294-297(1999).
RN [63]
RP VARIANTS HIS-265; ALA-326; PRO-385; ASN-406; THR-618 AND MET-716.
RX PubMed=10573010; DOI=10.1038/sj.ejhg.5200363;
RA Genuardi M., Carrara S., Anti M., Ponz de Leon M., Viel A.;
RT "Assessment of pathogenicity criteria for constitutional missense mutations
RT of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2.";
RL Eur. J. Hum. Genet. 7:778-782(1999).
RN [64]
RP VARIANTS HNPCC2 LEU-28; GLU-84 AND PRO-329.
RX PubMed=10323887; DOI=10.1136/gut.44.6.839;
RA Lamberti C., Kruse R., Ruelfs C., Caspari R., Wang Y., Jungck M.,
RA Mathiak M., Malayeri H.R.H., Friedl W., Sauerbruch T., Propping P.;
RT "Microsatellite instability, a useful diagnostic tool to select patients at
RT high risk for hereditary non-polyposis colorectal cancer: a study in
RT different groups of patients with colorectal cancer.";
RL Gut 44:839-843(1999).
RN [65]
RP VARIANTS HNPCC2 TRP-67; MET-117; GLY-182 AND LYS-616 DEL, AND VARIANT HNPCC
RP TRP-755.
RX PubMed=10480359; DOI=10.1007/s004399900064;
RA Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C.,
RA Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A.;
RT "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6
RT genes in 75 French kindreds with nonpolyposis colorectal cancer.";
RL Hum. Genet. 105:79-85(1999).
RN [66]
RP VARIANT CRC GLY-578, AND VARIANT HNPCC2 ALA-618.
RX PubMed=10598809; DOI=10.1007/s004390051127;
RA Liu T., Tannergaerd P., Hackman P., Rubio C., Kressner U., Lindmark G.,
RA Hellgren D., Lambert B., Lindblom A.;
RT "Missense mutations in hMLH1 associated with colorectal cancer.";
RL Hum. Genet. 105:437-441(1999).
RN [67]
RP VARIANT HNPCC2 PHE-25, AND VARIANT TYR-718.
RX PubMed=10386556; DOI=10.1001/jama.281.24.2316;
RA Weber T.K., Chin H.-M., Rodriguez-Bigas M., Keitz B., Gilligan R.,
RA O'Malley L., Urf E., Diba N., Pazik J., Petrelli N.J.;
RT "Novel hMLH1 and hMSH2 germline mutations in African Americans with
RT colorectal cancer.";
RL JAMA 281:2316-2320(1999).
RN [68]
RP VARIANT HNPCC2 TYR-264.
RX PubMed=10413423; DOI=10.1093/jnci/91.14.1221;
RA Chan T.L., Yuen S.T., Chung L.P., Ho J.W.C., Kwan K.Y.M., Chan A.S.Y.,
RA Ho J.C.Y., Leung S.Y., Wyllie A.H.;
RT "Frequent microsatellite instability and mismatch repair gene mutations in
RT young Chinese patients with colorectal cancer.";
RL J. Natl. Cancer Inst. 91:1221-1226(1999).
RN [69]
RP VARIANTS HNPCC2 VAL-111 AND PRO-588, AND VARIANTS VAL-219 AND ASP-384.
RX PubMed=10777691; DOI=10.1006/bbrc.2000.2547;
RA Nomura S., Sugano K., Kashiwabara H., Taniguchi T., Fukayama N., Fujita S.,
RA Akasu T., Moriya Y., Ohhigashi S., Kakizoe T., Sekiya T.;
RT "Enhanced detection of deleterious and other germline mutations of hMSH2
RT and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.";
RL Biochem. Biophys. Res. Commun. 271:120-129(2000).
RN [70]
RP VARIANTS HNPCC2 HIS-607; ALA-618 AND LEU-659, AND VARIANT MET-213.
RX PubMed=10713887; DOI=10.1038/sj.ejhg.5200393;
RA Fidalgo P., Almeida M.R., West S., Gaspar C., Maia L., Wijnen J.,
RA Albuquerque C., Curtis A., Cravo M., Fodde R., Leitao C.N., Burn J.;
RT "Detection of mutations in mismatch repair genes in Portuguese families
RT with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method
RT approach.";
RL Eur. J. Hum. Genet. 8:49-53(2000).
RN [71]
RP VARIANT CRC ARG-260, AND VARIANT HNPCC2 VAL-304.
RX PubMed=10882759; DOI=10.1136/jmg.37.7.e7;
RA Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S.,
RA Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L.,
RA Mareni C.;
RT "Mutational germline analysis of hMSH2 and hMLH1 genes in early onset
RT colorectal cancer patients.";
RL J. Med. Genet. 37:E7-E7(2000).
RN [72]
RP ERRATUM OF PUBMED:10882759.
RA Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S.,
RA Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L.,
RA Mareni C.;
RL J. Med. Genet. 40:472-472(2003).
RN [73]
RP VARIANTS GASTRIC CANCER ARG-106; GLN-109 AND LYS-635, VARIANTS HNPCC2
RP GLY-234; ILE-321; HIS-485 AND ALA-631, AND VARIANT CRC ILE-472.
RX PubMed=12132870;
RA Kim J.C., Kim H.C., Roh S.A., Koo K.H., Lee D.H., Yu C.S., Lee J.H.,
RA Kim T.W., Lee H.I., Beck N.E., Bodmer W.F.;
RT "hMLH1 and hMSH2 mutations in families with familial clustering of gastric
RT cancer and hereditary non-polyposis colorectal cancer.";
RL Cancer Detect. Prev. 25:503-510(2001).
RN [74]
RP VARIANT HIS-607.
RX PubMed=11369138; DOI=10.1016/s0304-3835(01)00448-7;
RA Stone J.G., Coleman G., Gusterson B., Marossy A., Lakhani S.R., Ward A.,
RA Nash A., McKinna A., A'Hern R., Stratton M.R., Houlston R.S.;
RT "Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in
RT situ of the breast.";
RL Cancer Lett. 167:171-174(2001).
RN [75]
RP INVOLVEMENT IN TUMORIGENESIS.
RX PubMed=11389087;
RA Vilkki S., Tsao J.-L., Loukola A., Poyhonen M., Vierimaa O., Herva R.,
RA Aaltonen L.A., Shibata D.;
RT "Extensive somatic microsatellite mutations in normal human tissue.";
RL Cancer Res. 61:4541-4544(2001).
RN [76]
RP VARIANTS HNPCC2 VAL-80; PRO-329; ARG-603; ALA-618; LEU-648 AND PRO-662, AND
RP VARIANT HNPCC ARG-689.
RX PubMed=11726306;
RA Mueller-Koch Y., Kopp R., Lohse P., Baretton G., Stoetzer A., Aust D.,
RA Daum J., Kerker B., Gross M., Dietmeier W., Holinski-Feder E.;
RT "Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a
RT cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer)
RT patients: mutations or polymorphisms?";
RL Eur. J. Med. Res. 6:473-482(2001).
RN [77]
RP CHARACTERIZATION OF VARIANTS.
RX PubMed=11555625; DOI=10.1093/hmg/10.18.1889;
RA Ellison A.R., Lofing J., Bitter G.A.;
RT "Functional analysis of human MLH1 and MSH2 missense variants and hybrid
RT human-yeast MLH1 proteins in Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 10:1889-1900(2001).
RN [78]
RP VARIANT HNPCC2 ARG-751.
RX PubMed=11139242; DOI=10.1002/1098-1004(2001)17:1<52::aid-humu6>3.0.co;2-e;
RA Jakubowska A., Gorski B., Kurzawski G., Debniak T., Hadaczek P.,
RA Cybulski C., Kladny J., Oszurek O., Scott R.J., Lubinski J.;
RT "Optimization of experimental conditions for RNA-based sequencing of MLH1
RT and MSH2 genes.";
RL Hum. Mutat. 17:52-60(2001).
RN [79]
RP VARIANTS HNPCC2 HIS-622 AND TRP-687.
RX PubMed=11748856; DOI=10.1002/humu.1240;
RA Godino J., de La Hoya M., Diaz-Rubio E., Benito M., Caldes T.;
RT "Eight novel germline MLH1 and MSH2 mutations in hereditary non-polyposis
RT colorectal cancer families from Spain.";
RL Hum. Mutat. 18:549-549(2001).
RN [80]
RP VARIANTS HNPCC2 SER-338; ARG-603; THR-618 AND TYR-718.
RX PubMed=12095971; DOI=10.1007/bf02573891;
RA Rossi B.M., Lopes A., Oliveira Ferreira F., Nakagawa W.T.,
RA Napoli Ferreira C.C., Casali Da Rocha J.C., Simpson C.C., Simpson A.J.G.;
RT "hMLH1 and hMSH2 gene mutation in Brazilian families with suspected
RT hereditary nonpolyposis colorectal cancer.";
RL Ann. Surg. Oncol. 9:555-561(2002).
RN [81]
RP VARIANTS HNPCC2 ASN-35; HIS-38; MET-117 AND ALA-618.
RX PubMed=12373605; DOI=10.1038/sj.bjc.6600565;
RA Gille J.J.P., Hogervorst F.B.L., Pals G., Wijnen J.T., van Schooten R.J.,
RA Dommering C.J., Meijer G.A., Craanen M.E., Nederlof P.M., de Jong D.,
RA McElgunn C.J., Schouten J.P., Menko F.H.;
RT "Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected
RT by a novel mutation detection approach.";
RL Br. J. Cancer 87:892-897(2002).
RN [82]
RP VARIANTS VAL-219 AND VAL-655.
RX PubMed=12115348; DOI=10.1002/cncr.10606;
RA Baldinu P., Cossu A., Manca A., Satta M.P., Pisano M., Casula M.,
RA Dessole S., Pintus A., Tanda F., Palmieri G.;
RT "Microsatellite instability and mutation analysis of candidate genes in
RT unselected Sardinian patients with endometrial carcinoma.";
RL Cancer 94:3157-3168(2002).
RN [83]
RP CHARACTERIZATION OF VARIANTS HNPCC2 MET-117; GLY-185; CYS-217; ASP-244 AND
RP ALA-326, AND CHARACTERIZATION OF VARIANTS VAL-219 AND HIS-265.
RX PubMed=11781295; DOI=10.1053/gast.2002.30296;
RA Trojan J., Zeuzem S., Randolph A., Hemmerle C., Brieger A., Raedle J.,
RA Plotz G., Jiricny J., Marra G.;
RT "Functional analysis of hMLH1 variants and HNPCC-related mutations using a
RT human expression system.";
RL Gastroenterology 122:211-219(2002).
RN [84]
RP VARIANTS HNPCC2 CYS-385; HIS-607; THR-618 AND SER-648, AND VARIANT MET-213.
RX PubMed=11839723; DOI=10.1136/gut.50.3.405;
RA Cravo M., Afonso A.J., Lage P., Albuquerque C., Maia L., Lacerda C.,
RA Fidalgo P., Chaves P., Cruz C., Nobre-Leitao C.;
RT "Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1
RT mismatch repair genes: implications for genetic testing.";
RL Gut 50:405-412(2002).
RN [85]
RP CHARACTERIZATION OF VARIANTS HNPCC2 ARG-77; ARG-107 AND PRO-659, AND
RP CHARACTERIZATION OF VARIANT GLY-93.
RX PubMed=11793442; DOI=10.1002/gcc.1225.abs;
RA Nystroem-Lahti M., Perrera C., Raeschle M., Panyushkina-Seiler E.,
RA Marra G., Curci A., Quaresima B., Costanzo F., D'Urso M., Venuta S.,
RA Jiricny J.;
RT "Functional analysis of MLH1 mutations linked to hereditary nonpolyposis
RT colon cancer.";
RL Genes Chromosomes Cancer 33:160-167(2002).
RN [86]
RP VARIANT HNPCC2 PRO-662, AND VARIANT VAL-219.
RX PubMed=11754112; DOI=10.1002/humu.9004;
RA Krueger S., Plaschke J., Pistorius S., Jeske B., Haas S., Kraemer H.,
RA Hinterseher I., Bier A., Kreuz F.R., Theissig F., Saeger H.D.,
RA Schackert H.K.;
RT "Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis
RT colorectal cancer.";
RL Hum. Mutat. 19:82-82(2002).
RN [87]
RP VARIANTS HNPCC2 MET-117 AND PRO-247, AND VARIANTS VAL-219; ALA-618 AND
RP MET-716.
RX PubMed=12200596; DOI=10.1007/s00432-002-0361-2;
RA Ward R., Meldrum C., Williams R., Mokany E., Scott R., Turner J.,
RA Hawkins N., Burgess B., Groombridge C., Spigelman A.;
RT "Impact of microsatellite testing and mismatch repair protein expression on
RT the clinical interpretation of genetic testing in hereditary non-polyposis
RT colorectal cancer.";
RL J. Cancer Res. Clin. Oncol. 128:403-411(2002).
RN [88]
RP VARIANT HNPCC2 CYS-646, AND VARIANT ALA-618.
RX PubMed=11870161; DOI=10.1200/jco.2002.20.5.1203;
RA Scartozzi M., Bianchi F., Rosati S., Galizia E., Antolini A., Loretelli C.,
RA Piga A., Bearzi I., Cellerino R., Porfiri E.;
RT "Mutations of hMLH1 and hMSH2 in patients with suspected hereditary
RT nonpolyposis colorectal cancer: correlation with microsatellite instability
RT and abnormalities of mismatch repair protein expression.";
RL J. Clin. Oncol. 20:1203-1208(2002).
RN [89]
RP VARIANTS HNPCC2 PHE-19; LEU-28; MET-117; PRO-292; THR-681 AND TRP-687, AND
RP VARIANT VAL-219.
RX PubMed=12362047; DOI=10.1136/jmg.39.10.e65;
RA Kurzawski G., Suchy J., Kladny J., Safranow K., Jakubowska A., Elsakov P.,
RA Kucinskas V., Gardovski J., Irmejs A., Sibul H., Huzarski T., Byrski T.,
RA Debniak T., Cybulski C., Gronwald J., Oszurek O., Clark J., Gozdz S.,
RA Niepsuj S., Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A.,
RA Fiszer-Maliszewska L., Bebenek M., Sorokin D., Stawicka M., Godlewski D.,
RA Richter P., Brozek I., Wysocka B., Jawien A., Banaszkiewicz Z.,
RA Kowalczyk J., Czudowska D., Goretzki P.E., Moeslein G., Lubinski J.;
RT "Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland
RT and the Baltic States.";
RL J. Med. Genet. 39:E65-E65(2002).
RN [90]
RP VARIANTS HNPCC2 SER-29; ARG-67; LEU-185 AND ASP-244.
RX PubMed=12658575; DOI=10.1086/373963;
RA Wagner A., Barrows A., Wijnen J.T., van der Klift H., Franken P.F.,
RA Verkuijlen P., Nakagawa H., Geugien M., Jaghmohan-Changur S., Breukel C.,
RA Meijers-Heijboer H., Morreau H., van Puijenbroek M., Burn J., Coronel S.,
RA Kinarski Y., Okimoto R., Watson P., Lynch J.F., de la Chapelle A.,
RA Lynch H.T., Fodde R.;
RT "Molecular analysis of hereditary nonpolyposis colorectal cancer in the
RT United States: high mutation detection rate among clinically selected
RT families and characterization of an American founder genomic deletion of
RT the MSH2 gene.";
RL Am. J. Hum. Genet. 72:1088-1100(2003).
RN [91]
RP VARIANTS CRC 325-ARG--GLN-327 DEL; ARG-618 AND PRO-749.
RX PubMed=14504054; DOI=10.1093/annonc/mdg402;
RA Colombino M., Cossu A., Arba A., Manca A., Curci A., Avallone A.,
RA Comella G., Botti G., Scintu F., Amoruso M., D'Abbicco D., d'Agnessa M.R.,
RA Spanu A., Tanda F., Palmieri G.;
RT "Microsatellite instability and mutation analysis among southern Italian
RT patients with colorectal carcinoma: detection of different alterations
RT accounting for MLH1 and MSH2 inactivation in familial cases.";
RL Ann. Oncol. 14:1530-1536(2003).
RN [92]
RP VARIANT HNPCC2 PRO-586.
RX PubMed=12655562; DOI=10.1002/humu.9121;
RA Kruger S., Plaschke J., Jeske B., Gorgens H., Pistorius S.R., Bier A.,
RA Kreuz F.R., Theissig F., Aust D.E., Saeger H.D., Schackert H.K.;
RT "Identification of six novel MSH2 and MLH1 germline mutations in HNPCC.";
RL Hum. Mutat. 21:445-446(2003).
RN [93]
RP VARIANT CRC GLY-601.
RX PubMed=12655564; DOI=10.1002/humu.9123;
RA Chen-Shtoyerman R., Theodor L., Harmati E., Friedman E., Dacka S.,
RA Kopelman Y., Sternberg A., Zarivach R., Bar-Meir S., Fireman Z.;
RT "Genetic analysis of familial colorectal cancer in Israeli Arabs.";
RL Hum. Mutat. 21:446-447(2003).
RN [94]
RP VARIANTS HNPCC2 CYS-18; ASP-101; LYS-182; CYS-379; ARG-559 AND LYS-616 DEL.
RX PubMed=14635101; DOI=10.1002/humu.10291;
RA Taylor C.F., Charlton R.S., Burn J., Sheridan E., Taylor G.R.;
RT "Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-
RT polyposis colorectal cancer: identification of novel and recurrent
RT deletions by MLPA.";
RL Hum. Mutat. 22:428-433(2003).
RN [95]
RP VARIANT HNPCC2 SER-648.
RX PubMed=15139004; DOI=10.1002/gcc.20040;
RA Raevaara T.E., Gerdes A.-M., Loennqvist K.E., Tybjaerg-Hansen A.,
RA Abdel-Rahman W.M., Kariola R., Peltomaeki P., Nystroem-Lahti M.;
RT "HNPCC mutation MLH1 P648S makes the functional protein unstable, and
RT homozygosity predisposes to mild neurofibromatosis type 1.";
RL Genes Chromosomes Cancer 40:261-265(2004).
RN [96]
RP VARIANTS HNPCC2 CYS-217; GLY-282; LEU-542; PRO-542; PRO-549; PRO-574;
RP PRO-636; SER-640 AND MET-724.
RX PubMed=15365995; DOI=10.1002/humu.9277;
RA Shin Y.-K., Heo S.-C., Shin J.-H., Hong S.-H., Ku J.-L., Yoo B.-C.,
RA Kim I.-J., Park J.-G.;
RT "Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-
RT polyposis colorectal cancer families.";
RL Hum. Mutat. 24:351-351(2004).
RN [97]
RP ERRATUM OF PUBMED:15365995.
RA Shin Y.K., Heo S.C., Shin J.H., Hong S.H., Ku J.L., Yoo B.C., Kim I.J.,
RA Park J.G.;
RL Hum. Mutat. 25:224-224(2005).
RN [98]
RP VARIANTS HNPCC2 GLY-41 AND ASN-VAL-PHE-HIS-ILE-719 INS.
RX PubMed=15365996; DOI=10.1002/humu.9278;
RA Krueger S., Bier A., Plaschke J., Hoehl R., Aust D.E., Kreuz F.R.,
RA Pistorius S.R., Saeger H.D., Rothhammer V., Al-Taie O., Schackert H.K.;
RT "Ten novel MSH2 and MLH1 germline mutations in families with HNPCC.";
RL Hum. Mutat. 24:351-352(2004).
RN [99]
RP VARIANTS HNPCC2 VAL-21; ARG-67; ASN-68 AND LYS-616 DEL.
RX PubMed=14961575; DOI=10.1002/ijc.11718;
RA Cederquist K., Emanuelsson M., Goeransson I., Holinski-Feder E.,
RA Mueller-Koch Y., Golovleva I., Groenberg H.;
RT "Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double
RT primary cancers of the colorectum and the endometrium: a population-based
RT study in northern Sweden.";
RL Int. J. Cancer 109:370-376(2004).
RN [100]
RP ERRATUM OF PUBMED:14961575.
RA Cederquist K., Emanuelsson M., Goransson I., Holinski-Feder E.,
RA Muller-Koch Y., Golovleva I., Gronberg H.;
RL Int. J. Cancer 115:1011-1011(2005).
RN [101]
RP INVOLVEMENT IN HNPCC2 BY EPIGENETIC INHERITANCE.
RX PubMed=15064764; DOI=10.1038/ng1342;
RA Suter C.M., Martin D.I.K., Ward R.L.;
RT "Germline epimutation of MLH1 in individuals with multiple cancers.";
RL Nat. Genet. 36:497-501(2004).
RN [102]
RP VARIANT CRC HIS-132.
RX PubMed=15184898; DOI=10.1038/ng1374;
RA Lipkin S.M., Rozek L.S., Rennert G., Yang W., Chen P.-C., Hacia J.,
RA Hunt N., Shin B., Fodor S., Kokoris M., Greenson J.K., Fearon E., Lynch H.,
RA Collins F., Gruber S.B.;
RT "The MLH1 D132H variant is associated with susceptibility to sporadic
RT colorectal cancer.";
RL Nat. Genet. 36:694-699(2004).
RN [103]
RP VARIANTS HNPCC2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67;
RP GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247;
RP PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; LEU-648;
RP SER-648; LEU-654 AND PRO-659, VARIANTS SER-29; GLY-93; GLN-443; ALA-618;
RP CYS-646; GLN-659; THR-681 AND MET-716, CHARACTERIZATION OF VARIANTS HNPCC2
RP LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77;
RP VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL;
RP PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; THR-618; LEU-648; SER-648;
RP LEU-654 AND PRO-659, AND CHARACTERIZATION OF VARIANTS SER-29; GLY-93;
RP MET-213; VAL-219; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716.
RX PubMed=16083711; DOI=10.1053/j.gastro.2005.06.005;
RA Raevaara T.E., Korhonen M.K., Lohi H., Hampel H., Lynch E.,
RA Loennqvist K.E., Holinski-Feder E., Sutter C., McKinnon W., Duraisamy S.,
RA Gerdes A.-M., Peltomaeki P., Kohonen-Corish M., Mangold E., Macrae F.,
RA Greenblatt M., de la Chapelle A., Nystroem M.;
RT "Functional significance and clinical phenotype of nontruncating mismatch
RT repair variants of MLH1.";
RL Gastroenterology 129:537-549(2005).
RN [104]
RP VARIANTS HNPCC2 LEU-28; LYS-35; ARG-67; VAL-111; MET-117; PRO-292; THR-441;
RP LYS-618 DEL; PRO-623; ILE-657 DEL; THR-681; TRP-687 AND ARG-751.
RX PubMed=16451135; DOI=10.1111/j.1399-0004.2006.00550.x;
RA Kurzawski G., Suchy J., Lener M., Klujszo-Grabowska E., Kladny J.,
RA Safranow K., Jakubowska K., Jakubowska A., Huzarski T., Byrski T.,
RA Debniak T., Cybulski C., Gronwald J., Oszurek O., Oszutowska D.,
RA Kowalska E., Gozdz S., Niepsuj S., Slomski R., Plawski A.,
RA Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M.,
RA Sorokin D., Sasiadek M.M., Stembalska A., Grzebieniak Z., Kilar E.,
RA Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Limon J.,
RA Jawien A., Banaszkiewicz Z., Janiszewska H., Kowalczyk J., Czudowska D.,
RA Scott R.J., Lubinski J.;
RT "Germline MSH2 and MLH1 mutational spectrum including large rearrangements
RT in HNPCC families from Poland (update study).";
RL Clin. Genet. 69:40-47(2006).
RN [105]
RP VARIANT MMRCS1 ASN-35.
RX PubMed=17440981; DOI=10.1002/cncr.22697;
RG Rotterdam initiative on gastrointestinal hereditary tumors;
RA Poley J.-W., Wagner A., Hoogmans M.M.C.P., Menko F.H., Tops C., Kros J.M.,
RA Reddingius R.E., Meijers-Heijboer H., Kuipers E.J., Dinjens W.N.M.;
RT "Biallelic germline mutations of mismatch-repair genes: a possible cause
RT for multiple pediatric malignancies.";
RL Cancer 109:2349-2356(2007).
RN [106]
RP VARIANTS HNPCC2 LYS-102 AND GLN-474.
RX PubMed=17510385; DOI=10.1158/0008-5472.can-06-3509;
RA Takahashi M., Shimodaira H., Andreutti-Zaugg C., Iggo R., Kolodner R.D.,
RA Ishioka C.;
RT "Functional analysis of human MLH1 variants using yeast and in vitro
RT mismatch repair assays.";
RL Cancer Res. 67:4595-4604(2007).
RN [107]
RP INVOLVEMENT IN HNPCC2 BY GERMLINE EPIMUTATION.
RX PubMed=17301300; DOI=10.1056/nejmoa064522;
RA Hitchins M.P., Wong J.J.L., Suthers G., Suter C.M., Martin D.I.K.,
RA Hawkins N.J., Ward R.L.;
RT "Inheritance of a cancer-associated MLH1 germ-line epimutation.";
RL N. Engl. J. Med. 356:697-705(2007).
RN [108]
RP VARIANTS CRC GLU-67 AND THR-681, AND VARIANTS ALA-22; GLY-93; SER-309;
RP ASN-406; HIS-607; ALA-618; ARG-689; MET-716; TYR-718 AND ARG-751.
RX PubMed=18033691; DOI=10.1002/humu.20635;
RA Barnetson R.A., Cartwright N., van Vliet A., Haq N., Drew K.,
RA Farrington S., Williams N., Warner J., Campbell H., Porteous M.E.,
RA Dunlop M.G.;
RT "Classification of ambiguous mutations in DNA mismatch repair genes
RT identified in a population-based study of colorectal cancer.";
RL Hum. Mutat. 29:367-374(2008).
RN [109]
RP VARIANT HNPCC2 ILE-330 DEL, AND VARIANTS HIS-41; ARG-67; ARG-77; SER-98;
RP SER-101; ASP-101; LYS-116; MET-117; ASN-126; MET-213; SER-215; SER-216;
RP PHE-260; CYS-265; HIS-265; ASP-320; ALA-326; ILE-330 DEL; TRP-474; GLN-474;
RP ASP-539; PRO-549; THR-551; ARG-585; ARG-603; HIS-607; PRO-619; SER-640;
RP LEU-640; VAL-655; SER-656; ARG-666; THR-681 AND ARG-689.
RX PubMed=18561205; DOI=10.1002/humu.20796;
RA Tournier I., Vezain M., Martins A., Charbonnier F., Baert-Desurmont S.,
RA Olschwang S., Wang Q., Buisine M.P., Soret J., Tazi J., Frebourg T.,
RA Tosi M.;
RT "A large fraction of unclassified variants of the mismatch repair genes
RT MLH1 and MSH2 is associated with splicing defects.";
RL Hum. Mutat. 29:1412-1424(2008).
RN [110]
RP VARIANTS HNPCC2 CYS-233 DEL AND TRP-389, CHARACTERIZATION OF VARIANTS
RP HNPCC2 LEU-28; LYS-37; HIS-38; LYS-38; PHE-44; ARG-67; PRO-109; PRO-111;
RP MET-117; CYS-233 DEL; CYS-265; TRP-389; GLN-443; PRO-550; GLY-578; PHE-582;
RP ASP-589; ALA-618; CYS-646; LEU-648; LEU-654; PRO-659 AND VAL-716 DEL,
RP CHARACTERIZATION OF VARIANTS GLY-93; VAL-219; SER-403; ASN-406 AND MET-716,
RP INTERACTION WITH PMS2, INTERACTION WITH EXO1, AND SUBCELLULAR LOCATION.
RX PubMed=22753075; DOI=10.1002/humu.22153;
RA Andersen S.D., Liberti S.E., Luetzen A., Drost M., Bernstein I.,
RA Nilbert M., Dominguez M., Nystroem M., Hansen T.V., Christoffersen J.W.,
RA Jaeger A.C., de Wind N., Nielsen F.C., Toerring P.M., Rasmussen L.J.;
RT "Functional characterization of MLH1 missense variants identified in Lynch
RT syndrome patients.";
RL Hum. Mutat. 33:1647-1655(2012).
RN [111]
RP VARIANTS ARG-116; LEU-213; LEU-264; THR-423 AND HIS-725, AND
RP CHARACTERIZATION OF VARIANTS ARG-116; LEU-213; LEU-264; THR-423 AND
RP HIS-725.
RX PubMed=28494185; DOI=10.1080/15384047.2017.1326439;
RA Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E.,
RA Deshpande S., Hall M.J., Dunbrack R.L. Jr., Golemis E.A.;
RT "Functional analysis of rare variants in mismatch repair proteins augments
RT results from computation-based predictive methods.";
RL Cancer Biol. Ther. 18:519-533(2017).
CC -!- FUNCTION: Heterodimerizes with PMS2 to form MutL alpha, a component of
CC the post-replicative DNA mismatch repair system (MMR). DNA repair is
CC initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to
CC a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
CC Assembly of the MutL-MutS-heteroduplex ternary complex in presence of
CC RFC and PCNA is sufficient to activate endonuclease activity of PMS2.
CC It introduces single-strand breaks near the mismatch and thus generates
CC new entry points for the exonuclease EXO1 to degrade the strand
CC containing the mismatch. DNA methylation would prevent cleavage and
CC therefore assure that only the newly mutated DNA strand is going to be
CC corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp
CC loader subunits of DNA polymerase III, suggesting that it may play a
CC role to recruit the DNA polymerase III to the site of the MMR. Also
CC implicated in DNA damage signaling, a process which induces cell cycle
CC arrest and can lead to apoptosis in case of major DNA damages.
CC Heterodimerizes with MLH3 to form MutL gamma which plays a role in
CC meiosis. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974,
CC ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
CC ECO:0000269|PubMed:9311737}.
CC -!- SUBUNIT: Component of the DNA mismatch repair (MMR) complex composed at
CC least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer
CC of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and
CC MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6)
CC or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex
CC (PubMed:10783165). This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains
CC (PubMed:10097147). Interacts with MCM9; the interaction recruits MLH1
CC to chromatin (PubMed:26300262). Interacts MCM8 (PubMed:26300262).
CC Interacts with PMS2 (PubMed:11427529, PubMed:22753075). Interacts with
CC MBD4 (PubMed:10097147). Interacts with EXO1 (PubMed:11427529,
CC PubMed:11429708, PubMed:12414623, PubMed:14676842, PubMed:22753075).
CC Interacts with MTMR15/FAN1 (PubMed:20603073).
CC {ECO:0000269|PubMed:10097147, ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:11429708,
CC ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:14676842,
CC ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:22753075,
CC ECO:0000269|PubMed:26300262}.
CC -!- INTERACTION:
CC P40692; P63261: ACTG1; NbExp=7; IntAct=EBI-744248, EBI-351292;
CC P40692; P07355: ANXA2; NbExp=7; IntAct=EBI-744248, EBI-352622;
CC P40692; Q10567-3: AP1B1; NbExp=3; IntAct=EBI-744248, EBI-11978055;
CC P40692; P63010-2: AP2B1; NbExp=8; IntAct=EBI-744248, EBI-11529439;
CC P40692; Q9BX63: BRIP1; NbExp=14; IntAct=EBI-744248, EBI-3509650;
CC P40692; Q9BX70: BTBD2; NbExp=3; IntAct=EBI-744248, EBI-710091;
CC P40692; Q5JTZ5: C9orf152; NbExp=3; IntAct=EBI-744248, EBI-18560658;
CC P40692; Q8NA61: CBY2; NbExp=6; IntAct=EBI-744248, EBI-741724;
CC P40692; Q8NA61-2: CBY2; NbExp=11; IntAct=EBI-744248, EBI-11524851;
CC P40692; Q8N5R6: CCDC33; NbExp=4; IntAct=EBI-744248, EBI-740841;
CC P40692; Q96LY2-2: CCDC74B; NbExp=3; IntAct=EBI-744248, EBI-17967022;
CC P40692; Q96GN5: CDCA7L; NbExp=4; IntAct=EBI-744248, EBI-5278764;
CC P40692; O76039: CDKL5; NbExp=4; IntAct=EBI-744248, EBI-1752465;
CC P40692; P07858: CTSB; NbExp=7; IntAct=EBI-744248, EBI-715062;
CC P40692; P17661: DES; NbExp=7; IntAct=EBI-744248, EBI-1055572;
CC P40692; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-744248, EBI-744099;
CC P40692; Q86W67: FAM228A; NbExp=3; IntAct=EBI-744248, EBI-12958227;
CC P40692; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-744248, EBI-742802;
CC P40692; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-744248, EBI-6658203;
CC P40692; Q96NE9: FRMD6; NbExp=3; IntAct=EBI-744248, EBI-741729;
CC P40692; Q96NE9-2: FRMD6; NbExp=4; IntAct=EBI-744248, EBI-13213391;
CC P40692; Q16658: FSCN1; NbExp=7; IntAct=EBI-744248, EBI-351076;
CC P40692; P11142: HSPA8; NbExp=2; IntAct=EBI-744248, EBI-351896;
CC P40692; Q9ULR0: ISY1; NbExp=3; IntAct=EBI-744248, EBI-2557660;
CC P40692; P52292: KPNA2; NbExp=9; IntAct=EBI-744248, EBI-349938;
CC P40692; Q5T749: KPRP; NbExp=3; IntAct=EBI-744248, EBI-10981970;
CC P40692; O95232-2: LUC7L3; NbExp=3; IntAct=EBI-744248, EBI-19157865;
CC P40692; P43361: MAGEA8; NbExp=7; IntAct=EBI-744248, EBI-10182930;
CC P40692; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-744248, EBI-12516603;
CC P40692; O95243-2: MBD4; NbExp=3; IntAct=EBI-744248, EBI-6448717;
CC P40692; Q9NXL9: MCM9; NbExp=4; IntAct=EBI-744248, EBI-2804985;
CC P40692; Q9UHC1: MLH3; NbExp=4; IntAct=EBI-744248, EBI-3893094;
CC P40692; Q6PF18: MORN3; NbExp=3; IntAct=EBI-744248, EBI-9675802;
CC P40692; P29372-4: MPG; NbExp=3; IntAct=EBI-744248, EBI-10695618;
CC P40692; P20585: MSH3; NbExp=5; IntAct=EBI-744248, EBI-1164205;
CC P40692; P15173: MYOG; NbExp=12; IntAct=EBI-744248, EBI-3906629;
CC P40692; P60323-2: NANOS3; NbExp=3; IntAct=EBI-744248, EBI-18012223;
CC P40692; Q9H3P2: NELFA; NbExp=3; IntAct=EBI-744248, EBI-5461341;
CC P40692; Q14938-5: NFIX; NbExp=3; IntAct=EBI-744248, EBI-12024662;
CC P40692; O00746: NME4; NbExp=3; IntAct=EBI-744248, EBI-744871;
CC P40692; Q969T7: NT5C3B; NbExp=3; IntAct=EBI-744248, EBI-2932564;
CC P40692; O15055: PER2; NbExp=3; IntAct=EBI-744248, EBI-1054296;
CC P40692; P78356-2: PIP4K2B; NbExp=3; IntAct=EBI-744248, EBI-11532361;
CC P40692; P54277: PMS1; NbExp=4; IntAct=EBI-744248, EBI-2893308;
CC P40692; P54278: PMS2; NbExp=21; IntAct=EBI-744248, EBI-1162561;
CC P40692; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-744248, EBI-1105153;
CC P40692; Q6MZQ0: PRR5L; NbExp=3; IntAct=EBI-744248, EBI-1567866;
CC P40692; P25786: PSMA1; NbExp=5; IntAct=EBI-744248, EBI-359352;
CC P40692; P26045: PTPN3; NbExp=3; IntAct=EBI-744248, EBI-1047946;
CC P40692; Q6NSI4: RADX; NbExp=9; IntAct=EBI-744248, EBI-8634209;
CC P40692; Q5RL73: RBM48; NbExp=3; IntAct=EBI-744248, EBI-473821;
CC P40692; Q86UC2: RSPH3; NbExp=3; IntAct=EBI-744248, EBI-6873025;
CC P40692; Q6RVD6: SPATA8; NbExp=3; IntAct=EBI-744248, EBI-8635958;
CC P40692; Q13813: SPTAN1; NbExp=7; IntAct=EBI-744248, EBI-351450;
CC P40692; O95926: SYF2; NbExp=3; IntAct=EBI-744248, EBI-2557644;
CC P40692; Q5VWN6: TASOR2; NbExp=6; IntAct=EBI-744248, EBI-745958;
CC P40692; Q7Z6R9: TFAP2D; NbExp=5; IntAct=EBI-744248, EBI-11952651;
CC P40692; Q08117-2: TLE5; NbExp=3; IntAct=EBI-744248, EBI-11741437;
CC P40692; P62328: TMSB4X; NbExp=16; IntAct=EBI-744248, EBI-712598;
CC P40692; Q96PP4: TSGA13; NbExp=3; IntAct=EBI-744248, EBI-12390276;
CC P40692; Q01081: U2AF1; NbExp=3; IntAct=EBI-744248, EBI-632461;
CC P40692; O94941: UBOX5; NbExp=7; IntAct=EBI-744248, EBI-751901;
CC P40692; O75152: ZC3H11A; NbExp=7; IntAct=EBI-744248, EBI-748480;
CC P40692; Q9NU63-3: ZFP57; NbExp=3; IntAct=EBI-744248, EBI-12879708;
CC P40692; Q8TF47: ZFP90; NbExp=3; IntAct=EBI-744248, EBI-11419867;
CC P40692; Q9UDW3: ZMAT5; NbExp=3; IntAct=EBI-744248, EBI-7850213;
CC P40692; Q13360-2: ZNF177; NbExp=3; IntAct=EBI-744248, EBI-12272076;
CC P40692; Q9UDV6: ZNF212; NbExp=3; IntAct=EBI-744248, EBI-1640204;
CC P40692; Q6S9Z5: ZNF474; NbExp=3; IntAct=EBI-744248, EBI-17269964;
CC P40692; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-744248, EBI-10251462;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11429708,
CC ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:21120944,
CC ECO:0000269|PubMed:22753075}. Chromosome {ECO:0000269|PubMed:26300262}.
CC Note=Recruited to chromatin in a MCM9-dependent manner.
CC {ECO:0000269|PubMed:26300262}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P40692-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P40692-2; Sequence=VSP_045201;
CC Name=3;
CC IsoId=P40692-3; Sequence=VSP_047023;
CC -!- TISSUE SPECIFICITY: Colon, lymphocytes, breast, lung, spleen, testis,
CC prostate, thyroid, gall bladder and heart.
CC -!- DISEASE: Hereditary non-polyposis colorectal cancer 2 (HNPCC2)
CC [MIM:609310]: An autosomal dominant disease associated with marked
CC increase in cancer susceptibility. It is characterized by a familial
CC predisposition to early-onset colorectal carcinoma (CRC) and extra-
CC colonic tumors of the gastrointestinal, urological and female
CC reproductive tracts. HNPCC is reported to be the most common form of
CC inherited colorectal cancer in the Western world. Clinically, HNPCC is
CC often divided into two subgroups. Type I is characterized by hereditary
CC predisposition to colorectal cancer, a young age of onset, and
CC carcinoma observed in the proximal colon. Type II is characterized by
CC increased risk for cancers in certain tissues such as the uterus,
CC ovary, breast, stomach, small intestine, skin, and larynx in addition
CC to the colon. Diagnosis of classical HNPCC is based on the Amsterdam
CC criteria: 3 or more relatives affected by colorectal cancer, one a
CC first degree relative of the other two; 2 or more generation affected;
CC 1 or more colorectal cancers presenting before 50 years of age;
CC exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC'
CC or 'incomplete HNPCC' can be used to describe families who do not or
CC only partially fulfill the Amsterdam criteria, but in whom a genetic
CC basis for colon cancer is strongly suspected.
CC {ECO:0000269|PubMed:10323887, ECO:0000269|PubMed:10375096,
CC ECO:0000269|PubMed:10386556, ECO:0000269|PubMed:10413423,
CC ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10598809,
CC ECO:0000269|PubMed:10627141, ECO:0000269|PubMed:10660333,
CC ECO:0000269|PubMed:10671064, ECO:0000269|PubMed:10713887,
CC ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:10882759,
CC ECO:0000269|PubMed:11139242, ECO:0000269|PubMed:11427529,
CC ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:11748856,
CC ECO:0000269|PubMed:11754112, ECO:0000269|PubMed:11781295,
CC ECO:0000269|PubMed:11793442, ECO:0000269|PubMed:11839723,
CC ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:12095971,
CC ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596,
CC ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605,
CC ECO:0000269|PubMed:12655562, ECO:0000269|PubMed:12658575,
CC ECO:0000269|PubMed:14635101, ECO:0000269|PubMed:14961575,
CC ECO:0000269|PubMed:15064764, ECO:0000269|PubMed:15139004,
CC ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:15365996,
CC ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:16451135,
CC ECO:0000269|PubMed:17301300, ECO:0000269|PubMed:17510385,
CC ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:20020535,
CC ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075,
CC ECO:0000269|PubMed:7757073, ECO:0000269|PubMed:8566964,
CC ECO:0000269|PubMed:8571956, ECO:0000269|PubMed:8797773,
CC ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:8993976,
CC ECO:0000269|PubMed:9048925, ECO:0000269|PubMed:9067757,
CC ECO:0000269|PubMed:9218993, ECO:0000269|PubMed:9272156,
CC ECO:0000269|PubMed:9298827, ECO:0000269|PubMed:9311737,
CC ECO:0000269|PubMed:9326924, ECO:0000269|PubMed:9399661,
CC ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9718327,
CC ECO:0000269|PubMed:9833759, ECO:0000269|PubMed:9927034,
CC ECO:0000269|Ref.5}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Mismatch repair cancer syndrome 1 (MMRCS1) [MIM:276300]: An
CC autosomal recessive form of mismatch repair cancer syndrome, a
CC childhood cancer predisposition syndrome encompassing a broad tumor
CC spectrum. This includes hematological malignancies, central nervous
CC system tumors, Lynch syndrome-associated malignancies such as
CC colorectal tumors as well as multiple intestinal polyps, embryonic
CC tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature
CC reminiscent of neurofibromatosis type 1, are often found as first
CC manifestation of the underlying cancer. {ECO:0000269|PubMed:11427529,
CC ECO:0000269|PubMed:17440981, ECO:0000269|PubMed:7661930}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal
CC dominant disorder characterized by sebaceous neoplasms and visceral
CC malignancy. {ECO:0000269|PubMed:8751876}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in MLH1 may contribute to lobular carcinoma in
CC situ (LCIS), a non-invasive neoplastic disease of the breast.
CC -!- DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of
CC endometrium, the mucous lining of the uterus. Most endometrial cancers
CC are adenocarcinomas, cancers that begin in cells that make and release
CC mucus and other fluids. Note=Disease susceptibility is associated with
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Some epigenetic changes can be transmitted unchanged
CC through the germline (termed 'epigenetic inheritance'). Evidence that
CC this mechanism occurs in humans is provided by the identification of
CC individuals in whom 1 allele of the MLH1 gene is epigenetically
CC silenced throughout the soma (implying a germline event). These
CC individuals are affected by HNPCC but does not have identifiable
CC mutations in MLH1, even though it is silenced, which demonstrates that
CC an epimutation can phenocopy a genetic disease.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:10598809,
CC ECO:0000269|PubMed:10882759, ECO:0000269|PubMed:12132870,
CC ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:14504054,
CC ECO:0000269|PubMed:15184898, ECO:0000269|PubMed:18033691,
CC ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9032648,
CC ECO:0000269|PubMed:9087566, ECO:0000269|PubMed:9611074}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db;
CC URL="http://www.nfdht.nl/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MLH1ID149ch3p21.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mlh1/";
CC -!- WEB RESOURCE: Name=Colon cancer gene variant databases MutL homolog 1
CC (E.coli) (MLH1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/MLH1";
CC ---------------------------------------------------------------------------
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DR EMBL; U07343; AAC50285.1; -; mRNA.
DR EMBL; U07418; AAA17374.1; -; mRNA.
DR EMBL; U40978; AAA82079.1; -; Genomic_DNA.
DR EMBL; U40960; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40961; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40962; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40963; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40964; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40965; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40966; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40967; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40968; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40969; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40970; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40971; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40972; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40973; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40974; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40975; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40976; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U40977; AAA82079.1; JOINED; Genomic_DNA.
DR EMBL; U17857; AAA85687.1; -; Genomic_DNA.
DR EMBL; U17839; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17840; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17841; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17842; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17843; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17844; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17845; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17846; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17847; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17848; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17849; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17851; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17852; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17853; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17854; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17855; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; U17856; AAA85687.1; JOINED; Genomic_DNA.
DR EMBL; AY217549; AAO22994.1; -; Genomic_DNA.
DR EMBL; AK295359; BAG58325.1; -; mRNA.
DR EMBL; AK298324; BAG60576.1; -; mRNA.
DR EMBL; AK298583; BAG60773.1; -; mRNA.
DR EMBL; AK316074; BAH14445.1; -; mRNA.
DR EMBL; AK316264; BAH14635.1; -; mRNA.
DR EMBL; AC006583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64483.1; -; Genomic_DNA.
DR EMBL; BC006850; AAH06850.1; -; mRNA.
DR CCDS; CCDS2663.1; -. [P40692-1]
DR CCDS; CCDS54562.1; -. [P40692-3]
DR CCDS; CCDS54563.1; -. [P40692-2]
DR PIR; S43085; S43085.
DR RefSeq; NP_000240.1; NM_000249.3. [P40692-1]
DR RefSeq; NP_001161089.1; NM_001167617.1. [P40692-3]
DR RefSeq; NP_001161090.1; NM_001167618.1. [P40692-2]
DR RefSeq; NP_001161091.1; NM_001167619.1. [P40692-2]
DR RefSeq; NP_001245200.1; NM_001258271.1.
DR RefSeq; NP_001245202.1; NM_001258273.1. [P40692-2]
DR RefSeq; NP_001245203.1; NM_001258274.1. [P40692-2]
DR RefSeq; XP_005265220.1; XM_005265163.1.
DR RefSeq; XP_005265221.1; XM_005265164.1.
DR PDB; 3RBN; X-ray; 2.16 A; A/B=486-751.
DR PDB; 4P7A; X-ray; 2.30 A; A=1-347.
DR PDB; 5U5P; X-ray; 2.17 A; B/C=467-476.
DR PDB; 6WBA; X-ray; 2.15 A; B/C=466-476.
DR PDB; 6WBB; X-ray; 2.66 A; B/C=466-476.
DR PDB; 6WBC; X-ray; 2.15 A; B=466-476.
DR PDB; 7M60; X-ray; 2.30 A; B/C=466-476.
DR PDBsum; 3RBN; -.
DR PDBsum; 4P7A; -.
DR PDBsum; 5U5P; -.
DR PDBsum; 6WBA; -.
DR PDBsum; 6WBB; -.
DR PDBsum; 6WBC; -.
DR PDBsum; 7M60; -.
DR AlphaFoldDB; P40692; -.
DR SMR; P40692; -.
DR BioGRID; 110438; 228.
DR CORUM; P40692; -.
DR DIP; DIP-27601N; -.
DR IntAct; P40692; 186.
DR MINT; P40692; -.
DR STRING; 9606.ENSP00000231790; -.
DR GlyGen; P40692; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P40692; -.
DR MetOSite; P40692; -.
DR PhosphoSitePlus; P40692; -.
DR BioMuta; MLH1; -.
DR DMDM; 730028; -.
DR EPD; P40692; -.
DR jPOST; P40692; -.
DR MassIVE; P40692; -.
DR MaxQB; P40692; -.
DR PaxDb; P40692; -.
DR PeptideAtlas; P40692; -.
DR PRIDE; P40692; -.
DR ProteomicsDB; 19516; -.
DR ProteomicsDB; 4266; -.
DR ProteomicsDB; 55377; -. [P40692-1]
DR Antibodypedia; 4599; 822 antibodies from 45 providers.
DR CPTC; P40692; 2 antibodies.
DR DNASU; 4292; -.
DR Ensembl; ENST00000231790.8; ENSP00000231790.3; ENSG00000076242.16. [P40692-1]
DR Ensembl; ENST00000435176.5; ENSP00000402564.1; ENSG00000076242.16. [P40692-3]
DR Ensembl; ENST00000455445.6; ENSP00000398272.2; ENSG00000076242.16. [P40692-2]
DR Ensembl; ENST00000458205.6; ENSP00000402667.2; ENSG00000076242.16. [P40692-2]
DR Ensembl; ENST00000536378.5; ENSP00000444286.2; ENSG00000076242.16. [P40692-2]
DR Ensembl; ENST00000539477.6; ENSP00000443665.1; ENSG00000076242.16. [P40692-2]
DR Ensembl; ENST00000674019.1; ENSP00000501081.1; ENSG00000076242.16. [P40692-2]
DR GeneID; 4292; -.
DR KEGG; hsa:4292; -.
DR MANE-Select; ENST00000231790.8; ENSP00000231790.3; NM_000249.4; NP_000240.1.
DR UCSC; uc003cgl.4; human. [P40692-1]
DR CTD; 4292; -.
DR DisGeNET; 4292; -.
DR GeneCards; MLH1; -.
DR GeneReviews; MLH1; -.
DR HGNC; HGNC:7127; MLH1.
DR HPA; ENSG00000076242; Low tissue specificity.
DR MalaCards; MLH1; -.
DR MIM; 114500; phenotype.
DR MIM; 120436; gene.
DR MIM; 158320; phenotype.
DR MIM; 276300; phenotype.
DR MIM; 608089; phenotype.
DR MIM; 609310; phenotype.
DR neXtProt; NX_P40692; -.
DR OpenTargets; ENSG00000076242; -.
DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome.
DR Orphanet; 144; Lynch syndrome.
DR Orphanet; 587; Muir-Torre syndrome.
DR PharmGKB; PA240; -.
DR VEuPathDB; HostDB:ENSG00000076242; -.
DR eggNOG; KOG1979; Eukaryota.
DR GeneTree; ENSGT00800000124177; -.
DR InParanoid; P40692; -.
DR OMA; ANYHVKK; -.
DR OrthoDB; 735423at2759; -.
DR PhylomeDB; P40692; -.
DR TreeFam; TF300493; -.
DR PathwayCommons; P40692; -.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-HSA-5545483; Defective Mismatch Repair Associated With MLH1.
DR Reactome; R-HSA-5632987; Defective Mismatch Repair Associated With PMS2.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR SignaLink; P40692; -.
DR SIGNOR; P40692; -.
DR BioGRID-ORCS; 4292; 15 hits in 1088 CRISPR screens.
DR ChiTaRS; MLH1; human.
DR EvolutionaryTrace; P40692; -.
DR GeneWiki; MLH1; -.
DR GenomeRNAi; 4292; -.
DR Pharos; P40692; Tbio.
DR PRO; PR:P40692; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P40692; protein.
DR Bgee; ENSG00000076242; Expressed in tibialis anterior and 208 other tissues.
DR ExpressionAtlas; P40692; baseline and differential.
DR Genevisible; P40692; HS.
DR GO; GO:0005712; C:chiasma; IEA:Ensembl.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005715; C:late recombination nodule; IEA:Ensembl.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR GO; GO:0032389; C:MutLalpha complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000795; C:synaptonemal complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0032137; F:guanine/thymine mispair binding; IEA:Ensembl.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IEA:Ensembl.
DR GO; GO:0016321; P:female meiosis chromosome segregation; IEA:Ensembl.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0007060; P:male meiosis chromosome segregation; IEA:Ensembl.
DR GO; GO:0043060; P:meiotic metaphase I plate congression; IEA:Ensembl.
DR GO; GO:0051257; P:meiotic spindle midzone assembly; IEA:Ensembl.
DR GO; GO:0045141; P:meiotic telomere clustering; IEA:Ensembl.
DR GO; GO:0006298; P:mismatch repair; IGI:MGI.
DR GO; GO:0045950; P:negative regulation of mitotic recombination; IEA:Ensembl.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IEA:Ensembl.
DR GO; GO:0048477; P:oogenesis; IEA:Ensembl.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IEA:Ensembl.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR DisProt; DP03062; -.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR014762; DNA_mismatch_repair_CS.
DR InterPro; IPR002099; DNA_mismatch_repair_N.
DR InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR032189; Mlh1_C.
DR InterPro; IPR038973; MutL/Mlh/Pms.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR10073; PTHR10073; 1.
DR Pfam; PF01119; DNA_mis_repair; 1.
DR Pfam; PF16413; Mlh1_C; 1.
DR SMART; SM01340; DNA_mis_repair; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR TIGRFAMs; TIGR00585; mutl; 1.
DR PROSITE; PS00058; DNA_MISMATCH_REPAIR_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Chromosome; Disease variant; DNA damage; DNA repair;
KW Hereditary nonpolyposis colorectal cancer; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Tumor suppressor.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..756
FT /note="DNA mismatch repair protein Mlh1"
FT /id="PRO_0000178000"
FT REGION 355..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..650
FT /note="Interaction with EXO1"
FT /evidence="ECO:0000269|PubMed:11427529,
FT ECO:0000269|PubMed:11429708, ECO:0000269|PubMed:12414623,
FT ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:22753075"
FT COMPBIAS 358..378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..416
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..432
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..463
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26249686,
FT ECO:0007744|PDB:4P7A"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26249686,
FT ECO:0007744|PDB:4P7A"
FT BINDING 82..84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26249686,
FT ECO:0007744|PDB:4P7A"
FT BINDING 100..104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:26249686,
FT ECO:0007744|PDB:4P7A"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..241
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045201"
FT VAR_SEQ 1..101
FT /note="MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVK
FT EGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG -> MAF
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047023"
FT VARIANT 18
FT /note="R -> C (in HNPCC2; dbSNP:rs367654552)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022663"
FT VARIANT 19
FT /note="I -> F (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750648)"
FT /evidence="ECO:0000269|PubMed:12362047"
FT /id="VAR_043383"
FT VARIANT 21
FT /note="A -> V (in HNPCC2; dbSNP:rs63750706)"
FT /evidence="ECO:0000269|PubMed:14961575"
FT /id="VAR_043384"
FT VARIANT 22
FT /note="G -> A (in dbSNP:rs41295280)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038023"
FT VARIANT 25
FT /note="I -> F (in HNPCC2; dbSNP:rs63749838)"
FT /evidence="ECO:0000269|PubMed:10386556"
FT /id="VAR_043385"
FT VARIANT 28
FT /note="P -> L (in HNPCC2; loss of protein expression;
FT normal interaction with PMS2 and EXO1; decreased mismatch
FT repair activity; no effect on nuclear localization;
FT dbSNP:rs63750792)"
FT /evidence="ECO:0000269|PubMed:10323887,
FT ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:9298827"
FT /id="VAR_004433"
FT VARIANT 29
FT /note="A -> S (in HNPCC2; unknown pathological
FT significance; acts functionally like the wild-type protein;
FT dbSNP:rs63750656)"
FT /evidence="ECO:0000269|PubMed:12658575,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_043386"
FT VARIANT 31
FT /note="A -> C (in HNPCC2; requires 2 nucleotide
FT substitutions; decreased mismatch repair activity;
FT dbSNP:rs63749994)"
FT /evidence="ECO:0000269|PubMed:20020535"
FT /id="VAR_076338"
FT VARIANT 32
FT /note="I -> V (in dbSNP:rs2020872)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_014876"
FT VARIANT 35
FT /note="M -> K (in HNPCC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16451135"
FT /id="VAR_043387"
FT VARIANT 35
FT /note="M -> N (in MMRCS1; requires 2 nucleotide
FT substitutions; dbSNP:rs121912965)"
FT /evidence="ECO:0000269|PubMed:12373605,
FT ECO:0000269|PubMed:17440981"
FT /id="VAR_043388"
FT VARIANT 35
FT /note="M -> R (in HNPCC2; dbSNP:rs63749906)"
FT /id="VAR_004434"
FT VARIANT 37
FT /note="E -> ELNH (found in an endometrial cancer sample;
FT somatic mutation)"
FT /id="VAR_004435"
FT VARIANT 37
FT /note="E -> K (in HNPCC2; decreased mismatch repair
FT activity; loss of nuclear localization; dbSNP:rs63751012)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076339"
FT VARIANT 38
FT /note="N -> H (in HNPCC2; decreased mismatch repair
FT activity; no effect on nuclear localization;
FT dbSNP:rs63750580)"
FT /evidence="ECO:0000269|PubMed:12373605,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:22753075"
FT /id="VAR_043389"
FT VARIANT 38
FT /note="N -> K (in HNPCC2; decreased mismatch repair
FT activity; no effect on nuclear localization;
FT dbSNP:rs267607706)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076340"
FT VARIANT 41
FT /note="D -> G (in HNPCC2; dbSNP:rs63751094)"
FT /evidence="ECO:0000269|PubMed:15365996"
FT /id="VAR_043390"
FT VARIANT 41
FT /note="D -> H (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607713)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054522"
FT VARIANT 44
FT /note="S -> F (in HNPCC2; no effect on MLH1 splicing; loss
FT of mismatch repair activity; dbSNP:rs63751109)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:9326924"
FT /id="VAR_004436"
FT VARIANT 45..47
FT /note="TSI -> CF (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression; loss of nuclear
FT localization)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_043391"
FT VARIANT 54
FT /note="G -> E (in CRC; sporadic; somatic mutation; unknown
FT pathological significance; dbSNP:rs63751267)"
FT /evidence="ECO:0000269|PubMed:9087566"
FT /id="VAR_012902"
FT VARIANT 62
FT /note="Q -> K (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63751428)"
FT /evidence="ECO:0000269|PubMed:9311737"
FT /id="VAR_004437"
FT VARIANT 63
FT /note="D -> E (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression; loss of nuclear
FT localization; dbSNP:rs587778955)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043392"
FT VARIANT 64
FT /note="N -> S (in HNPCC2; dbSNP:rs63750952)"
FT /evidence="ECO:0000269|PubMed:9311737"
FT /id="VAR_004438"
FT VARIANT 67
FT /note="G -> E (in CRC; dbSNP:rs63749939)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038024"
FT VARIANT 67
FT /note="G -> R (in HNPCC2; no effect on MLH1 splicing;
FT decreased mismatch repair activity; loss of protein
FT expression; loss of nuclear localization;
FT dbSNP:rs63750206)"
FT /evidence="ECO:0000269|PubMed:10375096,
FT ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14961575,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075,
FT ECO:0000269|PubMed:9067757, ECO:0000269|PubMed:9833759"
FT /id="VAR_004439"
FT VARIANT 67
FT /note="G -> W (in HNPCC2; dbSNP:rs63750206)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:9927034"
FT /id="VAR_012903"
FT VARIANT 68
FT /note="I -> N (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63750281)"
FT /evidence="ECO:0000269|PubMed:14961575"
FT /id="VAR_004440"
FT VARIANT 69
FT /note="R -> K (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63751661)"
FT /evidence="ECO:0000269|PubMed:10627141"
FT /id="VAR_004441"
FT VARIANT 71
FT /note="Missing (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043393"
FT VARIANT 77
FT /note="C -> R (in HNPCC2; decreased mismatch repair
FT activity; loss of nuclear localization; normal interaction
FT with PMS2; dbSNP:rs63749859)"
FT /evidence="ECO:0000269|PubMed:10660333,
FT ECO:0000269|PubMed:11793442, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:21120944"
FT /id="VAR_004442"
FT VARIANT 77
FT /note="C -> Y (in CRC; sporadic; early onset;
FT dbSNP:rs63750437)"
FT /evidence="ECO:0000269|PubMed:9032648"
FT /id="VAR_012904"
FT VARIANT 80
FT /note="F -> V (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63749990)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_012905"
FT VARIANT 84
FT /note="K -> E (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63750641)"
FT /evidence="ECO:0000269|PubMed:10323887,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_012906"
FT VARIANT 93
FT /note="S -> G (normal interaction with PMS2; no decrease in
FT mismatch repair activity; no effect on nuclear
FT localization; dbSNP:rs41295282)"
FT /evidence="ECO:0000269|PubMed:10671064,
FT ECO:0000269|PubMed:11793442, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075"
FT /id="VAR_004443"
FT VARIANT 98
FT /note="G -> S (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607725)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054523"
FT VARIANT 101
FT /note="G -> D (in HNPCC2; no effect on MLH1 splicing;
FT dbSNP:rs267607727)"
FT /evidence="ECO:0000269|PubMed:14635101,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_022664"
FT VARIANT 101
FT /note="G -> S (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607726)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054524"
FT VARIANT 102
FT /note="E -> K (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750453)"
FT /evidence="ECO:0000269|PubMed:17510385"
FT /id="VAR_043394"
FT VARIANT 106
FT /note="S -> R (in gastric cancer; unknown pathological
FT significance; dbSNP:rs63750297)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043395"
FT VARIANT 107
FT /note="I -> R (in HNPCC2; decreased mismatch repair
FT activity; normal interaction with PMS2; loss of protein
FT expression; loss of nuclear localization;
FT dbSNP:rs63750507)"
FT /evidence="ECO:0000269|PubMed:11793442,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_004444"
FT VARIANT 109
FT /note="H -> P (in HNPCC2; decreased mismatch repair
FT activity; no effect on nuclear localization;
FT dbSNP:rs587779004)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076341"
FT VARIANT 109
FT /note="H -> Q (in gastric cancer; unknown pathological
FT significance; dbSNP:rs63749803)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043396"
FT VARIANT 111
FT /note="A -> P (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs587779005)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076342"
FT VARIANT 111
FT /note="A -> V (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750539)"
FT /evidence="ECO:0000269|PubMed:10777691,
FT ECO:0000269|PubMed:16451135"
FT /id="VAR_012907"
FT VARIANT 116
FT /note="T -> K (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs63750465)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054525"
FT VARIANT 116
FT /note="T -> R (no effect on protein expression;
FT dbSNP:rs63750465)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079812"
FT VARIANT 117
FT /note="T -> M (in HNPCC2; decreased mismatch repair
FT activity; no effect on MLH1 splicing; fails to interact
FT with PMS2 and EXO1; loss of nuclear localization;
FT dbSNP:rs63750781)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:11429708, ECO:0000269|PubMed:11781295,
FT ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:8566964"
FT /id="VAR_004445"
FT VARIANT 117
FT /note="T -> R (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63750781)"
FT /evidence="ECO:0000269|PubMed:10375096"
FT /id="VAR_004446"
FT VARIANT 126
FT /note="Y -> N (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs200076893)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054526"
FT VARIANT 128
FT /note="A -> P (in HNPCC2; dbSNP:rs63750866)"
FT /evidence="ECO:0000269|PubMed:9218993"
FT /id="VAR_012908"
FT VARIANT 132
FT /note="D -> H (in CRC; sporadic; susceptibility to; ATPase
FT function attenuated but not eliminated; dbSNP:rs28930073)"
FT /evidence="ECO:0000269|PubMed:15184898"
FT /id="VAR_022665"
FT VARIANT 155
FT /note="L -> R (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression; loss of nuclear
FT localization; dbSNP:rs63750891)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043397"
FT VARIANT 182
FT /note="R -> G (in HNPCC2; incomplete; dbSNP:rs63750211)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:9399661"
FT /id="VAR_012909"
FT VARIANT 182
FT /note="R -> K (in HNPCC2; dbSNP:rs587779021)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022666"
FT VARIANT 185
FT /note="V -> G (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression; loss of nuclear
FT localization; no effect on MLH1 splicing;
FT dbSNP:rs63750515)"
FT /evidence="ECO:0000269|PubMed:11781295,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_004447"
FT VARIANT 185
FT /note="V -> L (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750012)"
FT /evidence="ECO:0000269|PubMed:12658575"
FT /id="VAR_043398"
FT VARIANT 193
FT /note="S -> P (in HNPCC2; dbSNP:rs63751021)"
FT /evidence="ECO:0000269|PubMed:10660333"
FT /id="VAR_004448"
FT VARIANT 213
FT /note="V -> L (no effect on protein expression;
FT dbSNP:rs2308317)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079813"
FT VARIANT 213
FT /note="V -> M (no effect on MLH1 splicing;
FT dbSNP:rs2308317)"
FT /evidence="ECO:0000269|PubMed:10713887,
FT ECO:0000269|PubMed:11839723, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:21120944,
FT ECO:0000269|Ref.5"
FT /id="VAR_012910"
FT VARIANT 215
FT /note="N -> S (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607775)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054527"
FT VARIANT 216
FT /note="I -> S (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607776)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054528"
FT VARIANT 217
FT /note="R -> C (in HNPCC2; unknown pathological
FT significance; no decrease in mismatch repair activity;
FT dbSNP:rs4986984)"
FT /evidence="ECO:0000269|PubMed:11781295,
FT ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:8797773,
FT ECO:0000269|PubMed:9559627"
FT /id="VAR_004449"
FT VARIANT 217
FT /note="R -> G"
FT /id="VAR_020469"
FT VARIANT 219
FT /note="I -> V (no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs1799977)"
FT /evidence="ECO:0000269|PubMed:10375096,
FT ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:11754112,
FT ECO:0000269|PubMed:11781295, ECO:0000269|PubMed:12115348,
FT ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075,
FT ECO:0000269|PubMed:9032648, ECO:0000269|PubMed:9067757,
FT ECO:0000269|PubMed:9087566, ECO:0000269|PubMed:9218993,
FT ECO:0000269|PubMed:9833759, ECO:0000269|Ref.5"
FT /id="VAR_004450"
FT VARIANT 226..295
FT /note="Missing (in HNPCC2)"
FT /id="VAR_004452"
FT VARIANT 226
FT /note="R -> L (in HNPCC2; dbSNP:rs63751711)"
FT /evidence="ECO:0000269|PubMed:8566964"
FT /id="VAR_004451"
FT VARIANT 233
FT /note="Missing (in HNPCC2; loss of nuclear localization)"
FT /evidence="ECO:0000269|PubMed:22753075"
FT /id="VAR_076343"
FT VARIANT 234
FT /note="E -> G (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750696)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043399"
FT VARIANT 244
FT /note="G -> D (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63750303)"
FT /evidence="ECO:0000269|PubMed:11781295,
FT ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:9218993"
FT /id="VAR_012911"
FT VARIANT 244
FT /note="G -> V (in CRC; sporadic; somatic mutation; unknown
FT pathological significance; dbSNP:rs63750303)"
FT /evidence="ECO:0000269|PubMed:9087566"
FT /id="VAR_012912"
FT VARIANT 247
FT /note="S -> P (in HNPCC2; decreased mismatch repair
FT activity; loss of protein expression; loss of nuclear
FT localization; dbSNP:rs63750948)"
FT /evidence="ECO:0000269|PubMed:12200596,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944"
FT /id="VAR_043400"
FT VARIANT 260
FT /note="L -> F (in HNPCC2; unknown pathological
FT significance; no effect on MLH1 splicing;
FT dbSNP:rs63750642)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054529"
FT VARIANT 260
FT /note="L -> R (in CRC; dbSNP:rs63751283)"
FT /evidence="ECO:0000269|PubMed:10882759"
FT /id="VAR_043401"
FT VARIANT 262
FT /note="Missing (in HNPCC2)"
FT /evidence="ECO:0000269|PubMed:9833759"
FT /id="VAR_012913"
FT VARIANT 264
FT /note="H -> L (no effect on protein expression;
FT dbSNP:rs63751664)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079814"
FT VARIANT 264
FT /note="H -> Y (in HNPCC2; dbSNP:rs63751597)"
FT /evidence="ECO:0000269|PubMed:10413423"
FT /id="VAR_043402"
FT VARIANT 265
FT /note="R -> C (in HNPCC2; results in partial MLH1 exon 10
FT skipping on ex vivo splicing assay; decreased mismatch
FT repair activity; no effect on nuclear localization;
FT dbSNP:rs63751194)"
FT /evidence="ECO:0000269|PubMed:18561205,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:22753075"
FT /id="VAR_054530"
FT VARIANT 265
FT /note="R -> H (associated with HNPCC2; results in partial
FT MLH1 exon 10 skipping on ex vivo splicing assay; decreased
FT mismatch repair activity; dbSNP:rs63751448)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:11781295, ECO:0000269|PubMed:18561205,
FT ECO:0000269|PubMed:8993976"
FT /id="VAR_012914"
FT VARIANT 265
FT /note="R -> S (in HNPCC2; decreased mismatch repair
FT activity; dbSNP:rs63751194)"
FT /evidence="ECO:0000269|PubMed:20020535"
FT /id="VAR_076344"
FT VARIANT 268
FT /note="E -> G (in CRC; dbSNP:rs63750650)"
FT /evidence="ECO:0000269|PubMed:9611074"
FT /id="VAR_012915"
FT VARIANT 282
FT /note="A -> G (in HNPCC2; dbSNP:rs63750360)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043403"
FT VARIANT 292
FT /note="L -> P (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750517)"
FT /evidence="ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:16451135"
FT /id="VAR_043404"
FT VARIANT 295
FT /note="S -> T (in HNPCC2; dbSNP:rs63750144)"
FT /evidence="ECO:0000269|PubMed:9399661"
FT /id="VAR_012916"
FT VARIANT 304
FT /note="D -> V (in HNPCC2; dbSNP:rs63750993)"
FT /evidence="ECO:0000269|PubMed:10882759"
FT /id="VAR_043405"
FT VARIANT 309
FT /note="P -> S (in dbSNP:rs267607808)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038025"
FT VARIANT 320
FT /note="E -> D (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607811)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054531"
FT VARIANT 321
FT /note="S -> I (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750286)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043406"
FT VARIANT 325..327
FT /note="Missing (in CRC)"
FT /evidence="ECO:0000269|PubMed:14504054"
FT /id="VAR_043407"
FT VARIANT 325
FT /note="R -> Q (in CRC; sporadic; somatic mutation; unknown
FT pathological significance; dbSNP:rs63750268)"
FT /evidence="ECO:0000269|PubMed:9087566"
FT /id="VAR_012917"
FT VARIANT 326
FT /note="V -> A (in HNPCC2; no decrease in mismatch repair
FT activity; dbSNP:rs63751049)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:11781295, ECO:0000269|PubMed:18561205"
FT /id="VAR_004453"
FT VARIANT 329
FT /note="H -> P (in HNPCC2; loss of protein expression; loss
FT of nuclear localization; dbSNP:rs63750710)"
FT /evidence="ECO:0000269|PubMed:10323887,
FT ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:9272156"
FT /id="VAR_012918"
FT VARIANT 330
FT /note="Missing (in HNPCC2; results in weak MLH1 exon 11
FT skipping on ex vivo splicing assay; decreased mismatch
FT repair activity; loss of protein expression; loss of
FT nuclear localization; dbSNP:rs63751197)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:21120944"
FT /id="VAR_043408"
FT VARIANT 338
FT /note="N -> S (in HNPCC2; dbSNP:rs63751467)"
FT /evidence="ECO:0000269|PubMed:12095971"
FT /id="VAR_043409"
FT VARIANT 379
FT /note="Y -> C (in HNPCC2; dbSNP:rs143009528)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022667"
FT VARIANT 384
FT /note="V -> D (can be associated with HNPCC in some
FT populations; dbSNP:rs63750447)"
FT /evidence="ECO:0000269|PubMed:10777691,
FT ECO:0000269|PubMed:8609062, ECO:0000269|PubMed:9526167"
FT /id="VAR_004454"
FT VARIANT 385
FT /note="R -> C (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750760)"
FT /evidence="ECO:0000269|PubMed:11839723"
FT /id="VAR_043410"
FT VARIANT 385
FT /note="R -> P (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750430)"
FT /evidence="ECO:0000269|PubMed:10573010"
FT /id="VAR_043411"
FT VARIANT 389
FT /note="R -> W (in HNPCC2; unknown pathological
FT significance; no effect on nuclear localization; normal
FT interaction with PMS2 and EXO1; dbSNP:rs61751644)"
FT /evidence="ECO:0000269|PubMed:22753075"
FT /id="VAR_076345"
FT VARIANT 403
FT /note="P -> S (no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs587778897)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076346"
FT VARIANT 406
FT /note="S -> N (no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs41294980)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:9087566"
FT /id="VAR_012919"
FT VARIANT 423
FT /note="R -> T (no effect on protein expression;
FT dbSNP:rs370687064)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079815"
FT VARIANT 441
FT /note="A -> T (in HNPCC2; dbSNP:rs63750365)"
FT /evidence="ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:9326924"
FT /id="VAR_012920"
FT VARIANT 443
FT /note="K -> Q (in HNPCC2; unknown pathological
FT significance; no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs34213726)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_043412"
FT VARIANT 460
FT /note="E -> A (in HNPCC2; unknown pathological
FT significance; dbSNP:rs202038499)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076347"
FT VARIANT 472
FT /note="R -> I (in CRC; unknown pathological significance;
FT dbSNP:rs63750498)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043413"
FT VARIANT 474
FT /note="R -> Q (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63751083)"
FT /evidence="ECO:0000269|PubMed:17510385,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_043414"
FT VARIANT 474
FT /note="R -> W (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs147939838)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054532"
FT VARIANT 485
FT /note="D -> E (in HNPCC2; dbSNP:rs63750956)"
FT /evidence="ECO:0000269|PubMed:10375096"
FT /id="VAR_043415"
FT VARIANT 485
FT /note="D -> H (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750314)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043416"
FT VARIANT 492
FT /note="A -> T (in HNPCC2; also found in sporadic colorectal
FT cancer; dbSNP:rs63751145)"
FT /evidence="ECO:0000269|PubMed:8872463"
FT /id="VAR_004455"
FT VARIANT 506
FT /note="V -> A (in HNPCC2; dbSNP:rs63749909)"
FT /id="VAR_004456"
FT VARIANT 539
FT /note="A -> D (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607843)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054533"
FT VARIANT 542
FT /note="Q -> L (in HNPCC2; type II; decreased mismatch
FT repair activity; dbSNP:rs63750511)"
FT /evidence="ECO:0000269|PubMed:15365995,
FT ECO:0000269|PubMed:7757073, ECO:0000269|PubMed:8797773"
FT /id="VAR_004457"
FT VARIANT 542
FT /note="Q -> P (in HNPCC2; dbSNP:rs63750511)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043417"
FT VARIANT 549
FT /note="L -> P (in HNPCC2; no effect on MLH1 splicing;
FT dbSNP:rs63750289)"
FT /evidence="ECO:0000269|PubMed:15365995,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:8797773"
FT /id="VAR_012921"
FT VARIANT 550
FT /note="L -> P (in HNPCC2; decreased mismatch repair
FT activity; defective in interaction with PMS2 and EXO1; loss
FT of protein expression; may lose nuclear localization;
FT dbSNP:rs63750193)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_043418"
FT VARIANT 551
FT /note="N -> T (in HNPCC2; no effect on MLH1 splicing;
FT dbSNP:rs63750271)"
FT /evidence="ECO:0000269|PubMed:18561205,
FT ECO:0000269|PubMed:9399661, ECO:0000269|PubMed:9833759"
FT /id="VAR_012922"
FT VARIANT 559
FT /note="L -> R (in HNPCC2; dbSNP:rs63750059)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022668"
FT VARIANT 565
FT /note="I -> F (in HNPCC2; dbSNP:rs63750062)"
FT /evidence="ECO:0000269|PubMed:9833759"
FT /id="VAR_012923"
FT VARIANT 574
FT /note="L -> P (in HNPCC2; type I; abrogates interaction
FT with EXO1; dbSNP:rs63751608)"
FT /evidence="ECO:0000269|PubMed:11427529,
FT ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:7757073,
FT ECO:0000269|PubMed:8797773"
FT /id="VAR_004458"
FT VARIANT 578..632
FT /note="Missing (in HNPCC2; decreased mismatch repair
FT activity; defective in interaction with PMS2)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076348"
FT VARIANT 578
FT /note="E -> G (in HNPCC2 and CRC; unknown pathological
FT significance; no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs63751612)"
FT /evidence="ECO:0000269|PubMed:10598809,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:22753075"
FT /id="VAR_004459"
FT VARIANT 582
FT /note="L -> F (in HNPCC2; decreased mismatch repair
FT activity; no effect on nuclear localization;
FT dbSNP:rs63751713)"
FT /evidence="ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_076349"
FT VARIANT 582
FT /note="L -> V (in HNPCC2; type II; dbSNP:rs63751713)"
FT /evidence="ECO:0000269|PubMed:7757073"
FT /id="VAR_004460"
FT VARIANT 585
FT /note="L -> R (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607865)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054534"
FT VARIANT 586
FT /note="A -> P (in HNPCC2; dbSNP:rs63751176)"
FT /evidence="ECO:0000269|PubMed:12655562"
FT /id="VAR_015689"
FT VARIANT 588
FT /note="L -> P (in HNPCC2; dbSNP:rs63750575)"
FT /evidence="ECO:0000269|PubMed:10777691"
FT /id="VAR_012924"
FT VARIANT 589
FT /note="A -> D (in HNPCC2; decreased mismatch repair
FT activity; loss of interaction with PMS2 and EXO1; loss of
FT protein expression; may lose nuclear localization;
FT dbSNP:rs63750016)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_043419"
FT VARIANT 596
FT /note="Missing (in HNPCC2)"
FT /id="VAR_043420"
FT VARIANT 601
FT /note="D -> G (in CRC; unknown pathological significance;
FT dbSNP:rs63750718)"
FT /evidence="ECO:0000269|PubMed:12655564"
FT /id="VAR_043421"
FT VARIANT 603
FT /note="P -> R (in HNPCC2; unknown pathological
FT significance; no effect on MLH1 splicing;
FT dbSNP:rs63750876)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:12095971, ECO:0000269|PubMed:18561205"
FT /id="VAR_012925"
FT VARIANT 607
FT /note="L -> H (in HNPCC2; unknown pathological
FT significance; also found in lobular carcinoma in situ of
FT the breast; no effect on MLH1 splicing; dbSNP:rs41295284)"
FT /evidence="ECO:0000269|PubMed:10713887,
FT ECO:0000269|PubMed:11369138, ECO:0000269|PubMed:11839723,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:18561205"
FT /id="VAR_012926"
FT VARIANT 612
FT /note="Missing (in HNPCC2; loss of protein expression; loss
FT of nuclear localization)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043422"
FT VARIANT 616
FT /note="Missing (in HNPCC2 and MMRCS1; abrogates interaction
FT with EXO1; loss of protein expression; loss of nuclear
FT localization; no effect on MLH1 splicing)"
FT /evidence="ECO:0000269|PubMed:10480359,
FT ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:14635101,
FT ECO:0000269|PubMed:14961575, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:7661930,
FT ECO:0000269|PubMed:8571956, ECO:0000269|PubMed:8872463,
FT ECO:0000269|PubMed:8993976, ECO:0000269|PubMed:9311737"
FT /id="VAR_004461"
FT VARIANT 618
FT /note="K -> A (in HNPCC2; unknown pathological
FT significance; requires 2 nucleotide substitutions;
FT interacts weakly with PMS2; no decrease in mismatch repair
FT activity; no effect on nuclear localization;
FT dbSNP:rs35502531)"
FT /evidence="ECO:0000269|PubMed:10598809,
FT ECO:0000269|PubMed:10713887, ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:12200596,
FT ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075,
FT ECO:0000269|PubMed:9311737"
FT /id="VAR_004462"
FT VARIANT 618
FT /note="K -> R (in CRC; dbSNP:rs63750449)"
FT /evidence="ECO:0000269|PubMed:14504054"
FT /id="VAR_043424"
FT VARIANT 618
FT /note="K -> T (in HNPCC2; type II; loss of nuclear
FT localization; dbSNP:rs63750449)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:11839723, ECO:0000269|PubMed:12095971,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:7757073, ECO:0000269|PubMed:8872463"
FT /id="VAR_004463"
FT VARIANT 618
FT /note="Missing (in HNPCC2; dbSNP:rs63751247)"
FT /evidence="ECO:0000269|PubMed:16451135"
FT /id="VAR_043423"
FT VARIANT 619
FT /note="A -> P (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607866)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054535"
FT VARIANT 622
FT /note="L -> H (in HNPCC2; dbSNP:rs63750693)"
FT /evidence="ECO:0000269|PubMed:11748856"
FT /id="VAR_012927"
FT VARIANT 623
FT /note="A -> P (in HNPCC2; unknown pathological
FT significance; dbSNP:rs587778951)"
FT /evidence="ECO:0000269|PubMed:16451135"
FT /id="VAR_043425"
FT VARIANT 626..627
FT /note="FS -> ST (in HNPCC2)"
FT /id="VAR_004464"
FT VARIANT 631
FT /note="D -> A (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63750240)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043426"
FT VARIANT 633..663
FT /note="Missing (in HNPCC2; decreased mismatch repair
FT activity; defective in interaction with PMS2; loss of
FT protein expression; loss of nuclear localization)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076350"
FT VARIANT 635
FT /note="N -> K (in gastric cancer; unknown pathological
FT significance; dbSNP:rs63751047)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043427"
FT VARIANT 636
FT /note="L -> P (in HNPCC2; dbSNP:rs63750825)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043428"
FT VARIANT 640
FT /note="P -> L (associated with HNPCC2; no effect on MLH1
FT splicing; dbSNP:rs267607875)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054536"
FT VARIANT 640
FT /note="P -> S (in HNPCC2; no effect on MLH1 splicing;
FT dbSNP:rs63749792)"
FT /evidence="ECO:0000269|PubMed:15365995,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_043429"
FT VARIANT 646
FT /note="Y -> C (in HNPCC2; defective in interaction with
FT PMS2 and EXO1; no decrease in mismatch repair activity;
FT dbSNP:rs35045067)"
FT /evidence="ECO:0000269|PubMed:11870161,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075"
FT /id="VAR_043430"
FT VARIANT 648
FT /note="P -> L (in HNPCC2; unknown pathological
FT significance; defective in interaction with PMS2 and EXO1;
FT may lose nuclear localization; loss of protein expression;
FT no decrease in mismatch repair activity; dbSNP:rs63750610)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075"
FT /id="VAR_012928"
FT VARIANT 648
FT /note="P -> S (in HNPCC2; the protein is unstable; loss of
FT nuclear localization; loss of protein expression; no
FT decrease in mismatch repair activity; dbSNP:rs63750899)"
FT /evidence="ECO:0000269|PubMed:11839723,
FT ECO:0000269|PubMed:15139004, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_022669"
FT VARIANT 654
FT /note="P -> L (in HNPCC2; decreased mismatch repair
FT activity; defective in interaction with PMS2 and EXO1; loss
FT of protein expression; may lose nuclear localization;
FT dbSNP:rs63750726)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075"
FT /id="VAR_043431"
FT VARIANT 655
FT /note="I -> V (in HNPCC2; also found in an endometrial
FT cancer sample; no effect on MLH1 splicing;
FT dbSNP:rs55907433)"
FT /evidence="ECO:0000269|PubMed:12115348,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_043432"
FT VARIANT 656
FT /note="F -> S (in HNPCC2; no effect on MLH1 splicing;
FT dbSNP:rs267607876)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054537"
FT VARIANT 657
FT /note="Missing (in HNPCC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16451135"
FT /id="VAR_043433"
FT VARIANT 659
FT /note="R -> L (in HNPCC2; dbSNP:rs63749900)"
FT /evidence="ECO:0000269|PubMed:10713887,
FT ECO:0000269|PubMed:11427529"
FT /id="VAR_012929"
FT VARIANT 659
FT /note="R -> P (in HNPCC2; interacts only very weakly with
FT PMS2; abrogates interaction with EXO1; decreased mismatch
FT repair activity; may lose nuclear localization;
FT dbSNP:rs63749900)"
FT /evidence="ECO:0000269|PubMed:11793442,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:20020535,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075,
FT ECO:0000269|PubMed:9311737"
FT /id="VAR_004465"
FT VARIANT 659
FT /note="R -> Q (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63749900)"
FT /evidence="ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043434"
FT VARIANT 662
FT /note="T -> P (in HNPCC2; unknown pathological
FT significance; dbSNP:rs587778964)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:11754112"
FT /id="VAR_012930"
FT VARIANT 666
FT /note="W -> R (in HNPCC2; unknown pathological
FT significance; no effect on MLH1 splicing;
FT dbSNP:rs267607887)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054538"
FT VARIANT 681
FT /note="A -> T (in HNPCC2 and CRC; abrogates interaction
FT with EXO1; no decrease in mismatch repair activity;
FT dbSNP:rs63750217)"
FT /evidence="ECO:0000269|PubMed:11427529,
FT ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:16083711,
FT ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:21120944"
FT /id="VAR_004466"
FT VARIANT 687
FT /note="R -> W (in HNPCC2; unknown pathological
FT significance; dbSNP:rs63751275)"
FT /evidence="ECO:0000269|PubMed:11748856,
FT ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_012931"
FT VARIANT 689
FT /note="Q -> R (in HNPCC; unknown pathological significance;
FT dbSNP:rs63750702)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:18561205"
FT /id="VAR_012932"
FT VARIANT 716
FT /note="V -> M (no decrease in mismatch repair activity; no
FT effect on nuclear localization; dbSNP:rs35831931)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:12200596,
FT ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:9833759"
FT /id="VAR_012933"
FT VARIANT 718
FT /note="H -> Y (in HNPCC2; unknown pathological
FT significance; dbSNP:rs2020873)"
FT /evidence="ECO:0000269|PubMed:10386556,
FT ECO:0000269|PubMed:12095971, ECO:0000269|PubMed:18033691"
FT /id="VAR_004467"
FT VARIANT 719
FT /note="I -> INVFHI (in HNPCC2)"
FT /id="VAR_043435"
FT VARIANT 724
FT /note="L -> M (in HNPCC2; dbSNP:rs63749875)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043436"
FT VARIANT 725
FT /note="R -> H (reduces by 60% protein expression;
FT dbSNP:rs566928243)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079816"
FT VARIANT 729
FT /note="L -> V (in dbSNP:rs1800149)"
FT /id="VAR_004468"
FT VARIANT 749
FT /note="L -> P (in CRC; dbSNP:rs267607894)"
FT /evidence="ECO:0000269|PubMed:14504054"
FT /id="VAR_043437"
FT VARIANT 751
FT /note="K -> R (in HNPCC2; unknown pathological
FT significance; dbSNP:rs140195825)"
FT /evidence="ECO:0000269|PubMed:11139242,
FT ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:18033691"
FT /id="VAR_012934"
FT VARIANT 755
FT /note="R -> W (in HNPCC; incomplete; dbSNP:rs267607900)"
FT /evidence="ECO:0000269|PubMed:10480359"
FT /id="VAR_012935"
FT CONFLICT 352
FT /note="L -> H (in Ref. 6; BAG60773)"
FT /evidence="ECO:0000305"
FT CONFLICT 708..711
FT /note="Missing (in Ref. 4; AAA85687)"
FT /evidence="ECO:0000305"
FT HELIX 13..25
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 28..41
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:4P7A"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:4P7A"
FT TURN 73..77
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 110..118
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 146..154
FT /evidence="ECO:0007829|PDB:4P7A"
FT TURN 155..158
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 169..186
FT /evidence="ECO:0007829|PDB:4P7A"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 212..220
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 228..235
FT /evidence="ECO:0007829|PDB:4P7A"
FT TURN 236..239
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 240..247
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 257..262
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 270..281
FT /evidence="ECO:0007829|PDB:4P7A"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 322..335
FT /evidence="ECO:0007829|PDB:4P7A"
FT HELIX 504..516
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 519..526
FT /evidence="ECO:0007829|PDB:3RBN"
FT STRAND 529..543
FT /evidence="ECO:0007829|PDB:3RBN"
FT STRAND 546..551
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 552..566
FT /evidence="ECO:0007829|PDB:3RBN"
FT STRAND 572..581
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 582..590
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 604..626
FT /evidence="ECO:0007829|PDB:3RBN"
FT STRAND 634..641
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 650..652
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 653..662
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 669..684
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 688..690
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 712..718
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 720..724
FT /evidence="ECO:0007829|PDB:3RBN"
FT HELIX 732..735
FT /evidence="ECO:0007829|PDB:3RBN"
FT STRAND 737..745
FT /evidence="ECO:0007829|PDB:3RBN"
SQ SEQUENCE 756 AA; 84601 MW; C9231FC406C2CA20 CRC64;
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ
IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA
DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV
GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF
KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV
KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS
SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE
MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL
AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE
DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL
ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV
YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC
