LDLR_HUMAN
ID LDLR_HUMAN Reviewed; 860 AA.
AC P01130; B4DII3; B4DJZ8; B4DR00; B4DTQ3; C0JYY8; H0YLU8; H0YNT7; Q53ZD9;
AC Q59FQ1; Q9UDH7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 256.
DE RecName: Full=Low-density lipoprotein receptor;
DE Short=LDL receptor;
DE Flags: Precursor;
GN Name=LDLR;
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), SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=6091915; DOI=10.1016/0092-8674(84)90188-0;
RA Yamamoto T., Davis C.G., Brown M.S., Schneider W.J., Casey M.L.,
RA Goldstein J.L., Russell D.W.;
RT "The human LDL receptor: a cysteine-rich protein with multiple Alu
RT sequences in its mRNA.";
RL Cell 39:27-38(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2988123; DOI=10.1126/science.2988123;
RA Suedhof T.C., Goldstein J.L., Brown M.S., Russell D.W.;
RT "The LDL receptor gene: a mosaic of exons shared with different proteins.";
RL Science 228:815-822(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Jia S., Lv L., Sun H., Wang Q., Wang H., Zhan L., Yang Z.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6).
RC TISSUE=Hippocampus, Placenta, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D.,
RA Toth E.J., Krauss R.M., Nickerson D.A.;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [12]
RP PROTEIN SEQUENCE OF 186-210; 394-405; 441-449; 472-495; 521-541 AND
RP 605-617.
RC TISSUE=Cervix carcinoma;
RX PubMed=8127891; DOI=10.1073/pnas.91.5.1839;
RA Hofer F., Gruenberger M., Kowalski H., Machat H., Huettinger M.,
RA Kuechler E., Blaas D.;
RT "Members of the low density lipoprotein receptor family mediate cell entry
RT of a minor-group common cold virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1839-1842(1994).
RN [13]
RP FUNCTION, AND GLYCOSYLATION.
RX PubMed=3005267; DOI=10.1016/s0021-9258(17)35862-3;
RA Davis C.G., Elhammer A., Russell D.W., Schneider W.J., Kornfeld S.,
RA Brown M.S., Goldstein J.L.;
RT "Deletion of clustered O-linked carbohydrates does not impair function of
RT low density lipoprotein receptor in transfected fibroblasts.";
RL J. Biol. Chem. 261:2828-2838(1986).
RN [14]
RP MUTAGENESIS OF CYTOPLASMIC DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=3104336; DOI=10.1016/s0021-9258(18)61313-4;
RA Davis C.G., van Driel I.R., Russell D.W., Brown M.S., Goldstein J.L.;
RT "The low density lipoprotein receptor. Identification of amino acids in
RT cytoplasmic domain required for rapid endocytosis.";
RL J. Biol. Chem. 262:4075-4082(1987).
RN [15]
RP FUNCTION (MICROBIAL INFECTION) AS RECEPTOR OF HEPATITIS C VIRUS.
RX PubMed=10535997; DOI=10.1073/pnas.96.22.12766;
RA Agnello V., Abel G., Elfahal M., Knight G.B., Zhang Q.X.;
RT "Hepatitis C virus and other flaviviridae viruses enter cells via low
RT density lipoprotein receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:12766-12771(1999).
RN [16]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 TAT.
RX PubMed=11100124; DOI=10.1038/82199;
RA Liu Y., Jones M., Hingtgen C.M., Bu G., Laribee N., Tanzi R.E., Moir R.D.,
RA Nath A., He J.J.;
RT "Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-
RT related protein disrupts the neuronal metabolic balance of the receptor
RT ligands.";
RL Nat. Med. 6:1380-1387(2000).
RN [17]
RP INTERACTION WITH LDLRAP1.
RX PubMed=12221107; DOI=10.1074/jbc.m208539200;
RA He G., Gupta S., Yi M., Michaely P., Hobbs H.H., Cohen J.C.;
RT "ARH is a modular adaptor protein that interacts with the LDL receptor,
RT clathrin, and AP-2.";
RL J. Biol. Chem. 277:44044-44049(2002).
RN [18]
RP INTERACTION WITH ARRB1, AND MUTAGENESIS OF TYR-828 AND SER-854.
RX PubMed=12944399; DOI=10.1074/jbc.m309450200;
RA Wu J.-H., Peppel K., Nelson C.D., Lin F.-T., Kohout T.A., Miller W.E.,
RA Exum S.T., Freedman N.J.;
RT "The adaptor protein beta-arrestin2 enhances endocytosis of the low density
RT lipoprotein receptor.";
RL J. Biol. Chem. 278:44238-44245(2003).
RN [19]
RP GLYCOSYLATION AT ASN-657.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [20]
RP FUNCTION (MICROBIAL INFECTION) AS RECEPTOR OF HEPATITIS C VIRUS.
RX PubMed=12615904; DOI=10.1084/jem.20021756;
RA Bartosch B., Dubuisson J., Cosset F.-L.;
RT "Infectious hepatitis C virus pseudo-particles containing functional E1-E2
RT envelope protein complexes.";
RL J. Exp. Med. 197:633-642(2003).
RN [21]
RP INTERACTION WITH SNX17.
RX PubMed=14739284; DOI=10.1074/jbc.m313689200;
RA Burden J.J., Sun X.-M., Garcia Garcia A.B., Soutar A.K.;
RT "Sorting motifs in the intracellular domain of the low density lipoprotein
RT receptor interact with a novel domain of sorting nexin-17.";
RL J. Biol. Chem. 279:16237-16245(2004).
RN [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [24]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PCSK9.
RX PubMed=17461796; DOI=10.1111/j.1600-0854.2007.00562.x;
RA Nassoury N., Blasiole D.A., Tebon Oler A., Benjannet S., Hamelin J.,
RA Poupon V., McPherson P.S., Attie A.D., Prat A., Seidah N.G.;
RT "The cellular trafficking of the secretory proprotein convertase PCSK9 and
RT its dependence on the LDLR.";
RL Traffic 8:718-732(2007).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [26]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, CHARACTERIZATION OF VARIANT SAINT OMER
RP ASP-546, MUTAGENESIS OF LYS-811; LYS-816; LYS-830 AND CYS-839,
RP UBIQUITINATION, AND REGION.
RX PubMed=19520913; DOI=10.1126/science.1168974;
RA Zelcer N., Hong C., Boyadjian R., Tontonoz P.;
RT "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of
RT the LDL receptor.";
RL Science 325:100-104(2009).
RN [27]
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 [28]
RP INTERACTION WITH PCSK9.
RX PubMed=21149300; DOI=10.1074/jbc.m110.199042;
RA Yamamoto T., Lu C., Ryan R.O.;
RT "A two-step binding model of PCSK9 interaction with the low density
RT lipoprotein receptor.";
RL J. Biol. Chem. 286:5464-5470(2011).
RN [29]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH VESICULAR STOMATITIS
RP VIRUS GLYCOPROTEIN.
RX PubMed=23589850; DOI=10.1073/pnas.1214441110;
RA Finkelshtein D., Werman A., Novick D., Barak S., Rubinstein M.;
RT "LDL receptor and its family members serve as the cellular receptors for
RT vesicular stomatitis virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:7306-7311(2013).
RN [30]
RP IDENTIFICATION BY 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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [32]
RP INTERACTION WITH C.DIFFICILE TCDA (MICROBIAL INFECTION).
RX PubMed=31160825; DOI=10.1038/s41564-019-0464-z;
RA Tao L., Tian S., Zhang J., Liu Z., Robinson-McCarthy L., Miyashita S.I.,
RA Breault D.T., Gerhard R., Oottamasathien S., Whelan S.P.J., Dong M.;
RT "Sulfated glycosaminoglycans and low-density lipoprotein receptor
RT contribute to Clostridium difficile toxin A entry into cells.";
RL Nat. Microbiol. 4:1760-1769(2019).
RN [33]
RP STRUCTURE BY NMR OF 20-67.
RX PubMed=7603991; DOI=10.1073/pnas.92.14.6334;
RA Daly N.L., Scanlon M.J., Djordjevic J.T., Kroon P.A., Smith R.;
RT "Three-dimensional structure of a cysteine-rich repeat from the low-density
RT lipoprotein receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:6334-6338(1995).
RN [34]
RP STRUCTURE BY NMR OF 65-104.
RX PubMed=7578052; DOI=10.1021/bi00044a025;
RA Daly N.L., Djordjevic J.T., Kroon P.A., Smith R.;
RT "Three-dimensional structure of the second cysteine-rich repeat from the
RT human low-density lipoprotein receptor.";
RL Biochemistry 34:14474-14481(1995).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 196-232.
RX PubMed=9262405; DOI=10.1038/41798;
RA Fass D., Blacklow S.C., Kim P.S., Berger J.M.;
RT "Molecular basis of familial hypercholesterolaemia from structure of LDL
RT receptor module.";
RL Nature 388:691-693(1997).
RN [36]
RP STRUCTURE BY NMR OF 20-104, AND DISULFIDE BONDS.
RX PubMed=10933493; DOI=10.1110/ps.9.7.1282;
RA Kurniawan N.D., Atkins A.R., Bieri S., Brown C.J., Brereton I.M.,
RA Kroon P.A., Smith R.;
RT "NMR structure of a concatemer of the first and second ligand-binding
RT modules of the human low-density lipoprotein receptor.";
RL Protein Sci. 9:1282-1293(2000).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) OF 22-720, AND DISULFIDE BONDS.
RX PubMed=12459547; DOI=10.1126/science.1078124;
RA Rudenko G., Henry L., Henderson K., Ichtchenko K., Brown M.S.,
RA Goldstein J.L., Deisenhofer J.;
RT "Structure of the LDL receptor extracellular domain at endosomal pH.";
RL Science 298:2353-2358(2002).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 819-832 IN COMPLEX WITH LDLRAP1,
RP INTERACTION WITH LDLRAP1, CHARACTERIZATION OF VARIANT FHCL1 CYS-828,
RP MUTAGENESIS OF ILE-821 AND GLN-829, TOPOLOGY, AND MOTIF.
RX PubMed=22509010; DOI=10.1073/pnas.1114128109;
RA Dvir H., Shah M., Girardi E., Guo L., Farquhar M.G., Zajonc D.M.;
RT "Atomic structure of the autosomal recessive hypercholesterolemia
RT phosphotyrosine-binding domain in complex with the LDL-receptor tail.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:6916-6921(2012).
RN [39]
RP REVIEW ON FHCL1 VARIANTS.
RX PubMed=1301956; DOI=10.1002/humu.1380010602;
RA Hobbs H.H., Brown M.S., Goldstein J.L.;
RT "Molecular genetics of the LDL receptor gene in familial
RT hypercholesterolemia.";
RL Hum. Mutat. 1:445-466(1992).
RN [40]
RP REVIEW ON FHCL1 VARIANTS.
RX PubMed=9016531; DOI=10.1093/nar/25.1.172;
RA Varret M., Rabes J.-P., Collod-Beroud G., Junien J., Boileau C., Beroud C.;
RT "Software and database for the analysis of mutations in the human LDL
RT receptor gene.";
RL Nucleic Acids Res. 25:172-180(1997).
RN [41]
RP VARIANT FHCL1 47-ASP-GLY-48 DEL.
RX PubMed=3263645; DOI=10.1073/pnas.85.21.7912;
RA Leitersdorf E., Hobbs H.H., Fourie A.M., Jacobs M.,
RA van der Westhuyzen D.R., Coetzee G.A.;
RT "Deletion in the first cysteine-rich repeat of low density lipoprotein
RT receptor impairs its transport but not lipoprotein binding in fibroblasts
RT from a subject with familial hypercholesterolemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7912-7916(1988).
RN [42]
RP VARIANTS FHCL1 ASN-175; GLU-227 AND MET-429.
RX PubMed=2569482; DOI=10.1172/jci114258;
RA Leitersdorf E., van der Westhuyzen D.R., Coetzee G.A., Hobbs H.H.;
RT "Two common low density lipoprotein receptor gene mutations cause familial
RT hypercholesterolemia in Afrikaners.";
RL J. Clin. Invest. 84:954-961(1989).
RN [43]
RP VARIANT FHCL1 CYS-828.
RX PubMed=3955657; DOI=10.1016/0092-8674(86)90533-7;
RA Davis C.G., Lehrman M.A., Russell D.W., Anderson R.G.W., Brown M.S.,
RA Goldstein J.L.;
RT "The J.D. mutation in familial hypercholesterolemia: amino acid
RT substitution in cytoplasmic domain impedes internalization of LDL
RT receptors.";
RL Cell 45:15-24(1986).
RN [44]
RP VARIANTS FHCL1 TYR-90 AND LYS-140.
RX PubMed=8347689; DOI=10.1016/0925-4439(93)90156-u;
RA Rubinsztein D.C., Jialal I., Leitersdorf E., Coetzee G.A.,
RA van der Westhuyzen D.R.;
RT "Identification of two new LDL-receptor mutations causing homozygous
RT familial hypercholesterolemia in a South African of Indian origin.";
RL Biochim. Biophys. Acta 1182:75-82(1993).
RN [45]
RP VARIANTS FHCL1 GLY-87; LYS-228 AND TYR-667.
RX PubMed=2318961; DOI=10.1172/jci114531;
RA Leitersdorf E., Tobin E.J., Davignon J., Hobbs H.H.;
RT "Common low-density lipoprotein receptor mutations in the French Canadian
RT population.";
RL J. Clin. Invest. 85:1014-1023(1990).
RN [46]
RP VARIANT FHCL1 HIS-433.
RX PubMed=1446662; DOI=10.1111/j.1432-1033.1992.tb17383.x;
RA Miyake Y., Tajima S., Funahashi T., Yamamura T., Yamamoto A.;
RT "A point mutation of low-density-lipoprotein receptor causing rapid
RT degradation of the receptor.";
RL Eur. J. Biochem. 210:1-7(1992).
RN [47]
RP VARIANT FHCL1 GLY-218 DEL.
RX PubMed=1867200;
RA Meiner V., Landsberger D., Berkman N., Reshef A., Segal P., Seftel H.C.,
RA van der Westhuyzen D.R., Jeenah M.S., Coetzee G.A., Leitersdorf E.;
RT "A common Lithuanian mutation causing familial hypercholesterolemia in
RT Ashkenazi Jews.";
RL Am. J. Hum. Genet. 49:443-449(1991).
RN [48]
RP VARIANT FHCL1 HIS-168.
RX PubMed=8462973; DOI=10.1007/bf00222714;
RA Leitersdorf E., Reshef A., Meiner V., Dann E.J., Beigel Y.,
RA van Roggen F.G., van der Westhuyzen D.R., Coetzee G.A.;
RT "A missense mutation in the low density lipoprotein receptor gene causes
RT familial hypercholesterolemia in Sephardic Jews.";
RL Hum. Genet. 91:141-147(1993).
RN [49]
RP VARIANT FHCL1 PHE-318.
RX PubMed=8168830; DOI=10.1007/bf00202819;
RA Lelli N., Garuti R., Pedrazzi P., Ghisellini M., Simone M.L., Tiozzo R.,
RA Cattin L., Valenti M., Rolleri M., Bertolini S., Stefanutti C.,
RA Calandra S.;
RT "A new missense mutation (Cys297-->Phe) of the low density lipoprotein
RT receptor in Italian patients with familial hypercholesterolemia
RT (FHTrieste).";
RL Hum. Genet. 93:538-540(1994).
RN [50]
RP VARIANT FHCL1 LEU-685.
RX PubMed=2726768; DOI=10.1073/pnas.86.11.4166;
RA Soutar A.K., Knight B.L., Patel D.D.;
RT "Identification of a point mutation in growth factor repeat C of the low
RT density lipoprotein-receptor gene in a patient with homozygous familial
RT hypercholesterolemia that affects ligand binding and intracellular movement
RT of receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4166-4170(1989).
RN [51]
RP VARIANT FHCL1 LEU-685.
RX PubMed=1464748;
RA Rubinsztein D.C., Coetzee G.A., Marais A.D., Leitersdorf E., Seftel H.C.,
RA van der Westhuyzen D.R.;
RT "Identification and properties of the proline664-leucine mutant LDL
RT receptor in South Africans of Indian origin.";
RL J. Lipid Res. 33:1647-1655(1992).
RN [52]
RP VARIANTS FHCL1 PORI HIS-401 AND TURKU ASP-844.
RX PubMed=7573037;
RA Koivisto U.-M., Viikari J.S., Kontula K.;
RT "Molecular characterization of minor gene rearrangements in Finnish
RT patients with heterozygous familial hypercholesterolemia: identification of
RT two common missense mutations (Gly823-->Asp and Leu380-->His) and eight
RT rare mutations of the LDL receptor gene.";
RL Am. J. Hum. Genet. 57:789-797(1995).
RN [53]
RP VARIANTS FHCL1 LYS-140; SER-338 AND LEU-685.
RX PubMed=7583548; DOI=10.1161/01.atv.15.10.1713;
RA Maruyama T., Miyake Y., Tajima S., Harada-Shiba M., Yamamura T.,
RA Tsushima M., Kishino B., Horiguchi Y., Funahashi T., Matsuzawa Y.,
RA Yamamoto A.;
RT "Common mutations in the low-density-lipoprotein-receptor gene causing
RT familial hypercholesterolemia in the Japanese population.";
RL Arterioscler. Thromb. Vasc. Biol. 15:1713-1718(1995).
RN [54]
RP VARIANT FHCL1 FRENCH HIS-564.
RX PubMed=7550239; DOI=10.1002/humu.1380060117;
RA Tricot-Guerber F., Saint-Jore B., Valenti K., Foulon T., Bost M.,
RA Hadjian A.J.;
RT "Identification of a mutation, N543H, in exon 11 of the low-density
RT lipoprotein receptor gene in a French family with familial
RT hypercholesterolemia.";
RL Hum. Mutat. 6:87-88(1995).
RN [55]
RP VARIANTS FHCL1 LYS-277; THR-423 AND ASN-579.
RX PubMed=7635461; DOI=10.1007/bf00207370;
RA Ekstroem U., Abrahamson M., Sveger T., Lombardi P., Nilsson-Ehle P.;
RT "An efficient screening procedure detecting six novel mutations in the LDL
RT receptor gene in Swedish children with hypercholesterolemia.";
RL Hum. Genet. 96:147-150(1995).
RN [56]
RP VARIANT FHCL1 NORWEGIAN ASN-487 DEL.
RX PubMed=7635482; DOI=10.1007/bf00207391;
RA Leren T.P., Solberg K., Rodningen O.K., Tonstad S., Ose L.;
RT "Two novel point mutations in the EGF precursor homology domain of the LDL
RT receptor gene causing familial hypercholesterolemia.";
RL Hum. Genet. 96:241-242(1995).
RN [57]
RP VARIANTS FHCL1 COLOGNE GLY-221; TYR-221 AND VAL-224.
RX PubMed=7649546; DOI=10.1007/bf00210411;
RA Geisel J., Holzem G., Oette K.;
RT "Screening for mutations in exon 4 of the LDL receptor gene in a German
RT population with severe hypercholesterolemia.";
RL Hum. Genet. 96:301-304(1995).
RN [58]
RP VARIANTS FHCL1 LA HABANA LYS-277; MET-429 AND MET-797.
RX PubMed=7649549; DOI=10.1007/bf00210415;
RA Pereira E., Ferreira R., Hermelin B., Thomas G., Bernard C., Bertrand V.,
RA Nassiff H., Mendez del Castillo D., Bereziat G., Benlian P.;
RT "Recurrent and novel LDL receptor gene mutations causing heterozygous
RT familial hypercholesterolemia in La Habana.";
RL Hum. Genet. 96:319-322(1995).
RN [59]
RP VARIANTS FHCL1 TYR-168 AND ARG-366.
RX PubMed=8740918; DOI=10.1111/j.1399-0004.1996.tb04333.x;
RA Gundersen K.E., Solberg K., Rodningen O.K., Tonstad S., Ose L., Berg K.,
RA Leren T.P.;
RT "Two novel missense mutations in the LDL receptor gene causing familial
RT hypercholesterolemia.";
RL Clin. Genet. 49:85-87(1996).
RN [60]
RP VARIANT FHCL1 GLY-231.
RX PubMed=8664907;
RX DOI=10.1002/(sici)1098-1004(1996)7:1<70::aid-humu12>3.0.co;2-p;
RA Sundvold H., Solberg K., Tonstad S., Rodningen O.K., Ose L., Berg K.,
RA Leren T.P.;
RT "A common missense mutation (C210G) in the LDL receptor gene among
RT Norwegian familial hypercholesterolemia subjects.";
RL Hum. Mutat. 7:70-71(1996).
RN [61]
RP VARIANTS FHCL1 ARG-197; TYR-248; ALA-301; TRP-302 AND PRO-350.
RX PubMed=9026534;
RA Webb J.C., Sun X.-M., McCarthy S.N., Neuwirth C., Thompson G.R., Knigh B.,
RA Soutar A.K.;
RT "Characterization of mutations in the low density lipoprotein (LDL)-
RT receptor gene in patients with homozygous familial hypercholesterolemia,
RT and frequency of these mutations in FH patients in the United Kingdom.";
RL J. Lipid Res. 37:368-381(1996).
RN [62]
RP VARIANT FHCL1 LEU-685.
RX PubMed=9254862; DOI=10.1007/s004390050503;
RA Peeters A.V., van Gaal L.F., du Plessis L., Lombardi M.P.R., Havekes L.M.,
RA Kotze M.J.;
RT "Mutational and genetic origin of LDL receptor gene mutations detected in
RT both Belgian and Dutch familial hypercholesterolemics.";
RL Hum. Genet. 100:266-270(1997).
RN [63]
RP VARIANTS FHCL1 HIS-564 AND 799-LEU--PHE-801 DEL.
RX PubMed=9143924;
RX DOI=10.1002/(sici)1098-1004(1997)9:5<437::aid-humu10>3.0.co;2-3;
RA Jensen H.K., Jensen T.G., Faergeman O., Jensen L.G., Andresen B.S.,
RA Corydon M.J., Andreasen P.H., Hansen P.S., Heath F., Bolund L.,
RA Gregersen N.;
RT "Two mutations in the same low-density lipoprotein receptor allele act in
RT synergy to reduce receptor function in heterozygous familial
RT hypercholesterolemia.";
RL Hum. Mutat. 9:437-444(1997).
RN [64]
RP VARIANTS FHCL1 TRP-27; CYS-78; GLY-87; TYR-89; ASN-90; GLY-90; LYS-101;
RP TYR-160; ASN-168; LEU-177; GLY-221; GLU-227; ARG-286; TYR-313; TYR-327;
RP ASN-342; PRO-350; ASP-399; TRP-416; HIS-482; ARG-483; SER-526; ASP-549;
RP CYS-633; LEU-649 AND ILE-726.
RX PubMed=9259195;
RX DOI=10.1002/(sici)1098-1004(1997)10:2<116::aid-humu4>3.0.co;2-i;
RA Day I.N.M., Whittall R.A., O'Dell S.D., Haddad L., Bolla M.K., Gudnason V.,
RA Humphries S.E.;
RT "Spectrum of LDL receptor gene mutations in heterozygous familial
RT hypercholesterolemia.";
RL Hum. Mutat. 10:116-127(1997).
RN [65]
RP VARIANTS FHCL1 PRO-56; TYR-175; TYR-356; VAL-401 AND TRP-416.
RX PubMed=9104431; DOI=10.1046/j.1365-2796.1997.78119000.x;
RA Leren T.P., Tonstad S., Gundersen K.E., Bakken K.S., Rodningen O.K.,
RA Sundvold H., Ose L., Berg K.;
RT "Molecular genetics of familial hypercholesterolaemia in Norway.";
RL J. Intern. Med. 241:185-194(1997).
RN [66]
RP VARIANTS FHCL1 LEU-177; GLY-218 DEL; SER-564 AND GLU-592.
RX PubMed=9654205; DOI=10.1007/s004390050740;
RA Gorski B., Kubalska J., Naruszewicz M., Lubinski J.;
RT "LDL-R and Apo-B-100 gene mutations in Polish familial
RT hypercholesterolemias.";
RL Hum. Genet. 102:562-565(1998).
RN [67]
RP VARIANTS FHCL1 TRP-173 AND ARG-368.
RX PubMed=9452094; DOI=10.1002/humu.1380110173;
RA Couture P., Vohl M.-C., Gagne C., Gaudet D., Torres A.L., Lupien P.J.,
RA Despres J.-P., Labrie F., Simard J., Moorjani S.;
RT "Identification of three mutations in the low-density lipoprotein receptor
RT gene causing familial hypercholesterolemia among French Canadians.";
RL Hum. Mutat. Suppl. 1:S226-S231(1998).
RN [68]
RP VARIANTS FHCL1 GLN-416 AND MET-429.
RX PubMed=9452095; DOI=10.1002/humu.1380110174;
RA Thiart R., Loubser O., de Villiers J.N.P., Marx M.P., Zaire R., Raal F.J.,
RA Kotze M.J.;
RT "Two novel and two known low-density lipoprotein receptor gene mutations in
RT German patients with familial hypercholesterolemia.";
RL Hum. Mutat. Suppl. 1:S232-S233(1998).
RN [69]
RP VARIANTS FHCL1 TYR-329; ARG-414 AND MET-429.
RX PubMed=9452118; DOI=10.1002/humu.1380110197;
RA Mak Y.T., Zhang J., Chan Y.S., Mak T.W.L., Tomlinson B., Masarei J.R.L.,
RA Pang C.P.;
RT "Possible common mutations in the low density lipoprotein receptor gene in
RT Chinese.";
RL Hum. Mutat. Suppl. 1:S310-S313(1998).
RN [70]
RP VARIANTS FHCL1 GLU-92; GLY-95; ARG-116; LEU-177; GLY-221; TYR-221; LYS-277;
RP TYR-302; LYS-434; TYR-667 AND GLU-700.
RX PubMed=10206683;
RX DOI=10.1002/(sici)1098-1004(1998)11:5<413::aid-humu17>3.0.co;2-f;
RA Cenarro A., Jensen H.K., Casao E., Civeira F., Gonzalez-Bonillo J.,
RA Rodriguez-Rey J.C., Gregersen N., Pocovi M.;
RT "Identification of recurrent and novel mutations in the LDL receptor gene
RT in Spanish patients with familial hypercholesterolemia.";
RL Hum. Mutat. 11:413-413(1998).
RN [71]
RP VARIANT FHCL1 CHIETI-3 GLU-228 DELINS CYS-LYS.
RX PubMed=10660340;
RA Motti C., Bertolini S., Rampa P., Trovatello G., Liberatoscioli L.,
RA Calandra S., Federici G., Cortese C.;
RT "Two novel mutations consisting in minor gene rearrangements in the human
RT low density lipoprotein receptor gene in Italian patients affected by
RT familial hypercholesterolemia.";
RL Hum. Mutat. 12:290-290(1998).
RN [72]
RP VARIANT FHCL1 TYR-276.
RA Vergopoulos A., Bajari T., Jouma M., Aydin A., Boehring S., Luft F.C.,
RA Schuster H.;
RT "A novel single amino acid substitution in exon 6 of the low-density
RT lipoprotein receptor gene in a Syrian family.";
RL Hum. Mutat. 12:365-365(1998).
RN [73]
RP VARIANTS FHCL1 TYR-379 AND SER-608.
RX PubMed=9852677; DOI=10.1007/s100380050083;
RA Hirayama T., Yamaki E., Hata A., Tsuji M., Hashimoto K., Yamamoto M.,
RA Emi M.;
RT "Five familial hypercholesterolemic kindreds in Japan with novel mutations
RT of the LDL receptor gene.";
RL J. Hum. Genet. 43:250-254(1998).
RN [74]
RP VARIANT FHCL1 GLASCO TYR-184.
RX PubMed=9678702; DOI=10.1136/jmg.35.7.573;
RA Lee W.K., Haddad L., Macleod M.J., Dorrance A.M., Wilson D.J., Gaffney D.,
RA Dominiczak M.H., Packard C.J., Day I.N., Humphries S.E., Dominiczak A.F.;
RT "Identification of a common low density lipoprotein receptor mutation
RT (C163Y) in the west of Scotland.";
RL J. Med. Genet. 35:573-578(1998).
RN [75]
RP VARIANTS FHCL1 GLY-87; LYS-140; ASN-172; ARG-243; LEU-306; PRO-404;
RP HIS-564; SER-577; ASN-579; ILE-726 AND LYS-825.
RX PubMed=10532689; DOI=10.1016/s0021-9150(99)00158-6;
RA Jensen H.K., Jensen L.G., Meinertz H., Hansen P.S., Gregersen N.,
RA Faergeman O.;
RT "Spectrum of LDL receptor gene mutations in Denmark: implications for
RT molecular diagnostic strategy in heterozygous familial
RT hypercholesterolemia.";
RL Atherosclerosis 146:337-344(1999).
RN [76]
RP VARIANT FHCL1 PHE-261.
RX PubMed=10422803; DOI=10.1034/j.1399-0004.1999.550506.x;
RA Ekstroem U., Abrahamson M., Floren C.-H., Tollig H., Wettrell G.,
RA Nilsson G., Sun X.-M., Soutar A.K., Nilsson-Ehle P.;
RT "An individual with a healthy phenotype in spite of a pathogenic LDL
RT receptor mutation (C240F).";
RL Clin. Genet. 55:332-339(1999).
RN [77]
RP VARIANTS FHCL1 SER-50; ASN-221; LYS-288; VAL-432 AND HIS-564.
RX PubMed=10090484;
RX DOI=10.1002/(sici)1098-1004(1999)13:3<257::aid-humu15>3.0.co;2-a;
RA Ebhardt M., Schmidt H., Doerk T., Tietge U., Haas R., Manns M.-P.,
RA Schmidtke J., Stuhrmann M.;
RT "Mutation analysis in 46 German families with familial
RT hypercholesterolemia: identification of 8 new mutations.";
RL Hum. Mutat. 13:257-257(1999).
RN [78]
RP VARIANTS FHCL1 SER-338; LEU-403; THR-431; VAL-568 AND LYS-714.
RX PubMed=10447263;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<87::aid-humu14>3.0.co;2-n;
RA Hattori H., Nagano M., Iwata F., Homma Y., Egashira T., Okada T.;
RT "Identification of recurrent and novel mutations in the LDL receptor gene
RT in Japanese familial hypercholesterolemia.";
RL Hum. Mutat. 14:87-87(1999).
RN [79]
RP VARIANTS ARG-2; ILE-468 AND GLN-814.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [80]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [81]
RP VARIANTS FHCL1 PHE-134; TRP-134; TYR-222; PRO-254; ARG-276; ARG-318;
RP THR-370; GLY-415 AND TYR-579.
RX PubMed=10978268; DOI=10.1161/01.atv.20.9.e41;
RA Bertolini S., Cantafora A., Averna M., Cortese C., Motti C., Martini S.,
RA Pes G., Postiglione A., Stefanutti C., Blotta I., Pisciotta L., Rolleri M.,
RA Langheim S., Ghisellini M., Rabbone I., Calandra S.;
RT "Clinical expression of familial hypercholesterolemia in clusters of
RT mutations of the LDL receptor gene that cause a receptor-defective or
RT receptor-negative phenotype.";
RL Arterioscler. Thromb. Vasc. Biol. 20:E41-E52(2000).
RN [82]
RP VARIANT FHCL1 THR-451.
RX PubMed=10980548;
RX DOI=10.1002/1098-1004(200009)16:3<277::aid-humu24>3.0.co;2-y;
RA Miltiadous G., Elisaf M., Xenophontos S., Manoli P., Cariolou M.A.;
RT "Segregation of a novel LDLR gene mutation (I430T) with familial
RT hypercholesterolaemia in a Greek pedigree.";
RL Hum. Mutat. 16:277-277(2000).
RN [83]
RP VARIANT FHCL1 47-ASP-GLY-48 DEL, AND VARIANTS HIS-172; TRP-253; GLN-406;
RP LYS-408; LEU-699 AND GLN-814.
RX PubMed=10882754; DOI=10.1136/jmg.37.7.514;
RA Thiart R., Scholtz C.L., Vergotine J., Hoogendijk C.F., de Villiers J.N.P.,
RA Nissen H., Brusgaard K., Gaffney D., Hoffs M.S., Vermaak W.J.H.,
RA Kotze M.J.;
RT "Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in
RT Africans with familial hypercholesterolaemia.";
RL J. Med. Genet. 37:514-519(2000).
RN [84]
RP VARIANT FHCL1 SER-46.
RX PubMed=11298688; DOI=10.1034/j.1399-0004.2001.590414.x;
RA Takahashi M., Ikeda U., Takahashi S., Hattori H., Iwasaki T., Ishihara M.,
RA Egashira T., Honma S., Asano Y., Shimada K.A.;
RT "A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in
RT a patient with homozygous familial hypercholesterolemia.";
RL Clin. Genet. 59:290-292(2001).
RN [85]
RP INVOLVEMENT IN FHCL1, VARIANTS FHCL1 ARG-143; TYR-148; TRP-184; CYS-574;
RP ASP-639 AND ASP-806, AND VARIANTS TRP-257 AND ILE-742.
RX PubMed=11462246; DOI=10.1002/humu.1171;
RA Nauck M.S., Koester W., Doerfer K., Eckes J., Scharnagl H., Gierens H.,
RA Nissen H., Nauck M.A., Wieland H., Maerz W.;
RT "Identification of recurrent and novel mutations in the LDL receptor gene
RT in German patients with familial hypercholesterolemia.";
RL Hum. Mutat. 18:165-166(2001).
RN [86]
RP VARIANTS FHCL1 TYR-89; LYS-101; GLY-218 DEL; GLY-221; ASN-221; TYR-358;
RP PRO-479; HIS-482; ARG-677 AND LEU-685, AND FUNCTION.
RX PubMed=17142622; DOI=10.1136/jmg.2006.038356;
RG Simon Broome familial hyperlipidemia register group and scientific steering committee;
RA Humphries S.E., Whittall R.A., Hubbart C.S., Maplebeck S., Cooper J.A.,
RA Soutar A.K., Naoumova R., Thompson G.R., Seed M., Durrington P.N.,
RA Miller J.P., Betteridge D.J.B., Neil H.A.W.;
RT "Genetic causes of familial hypercholesterolaemia in patients in the UK:
RT relation to plasma lipid levels and coronary heart disease risk.";
RL J. Med. Genet. 43:943-949(2006).
RN [87]
RP VARIANTS FHCL1 THR-50; LEU-211; GLY-221; GLU-266; LYS-277; ARG-286;
RP ARG-314; ARG-352; LYS-408; THR-431; HIS-442; MET-523; GLY-577; THR-585 AND
RP LEU-685.
RX PubMed=17347910; DOI=10.1007/s10545-007-0563-5;
RA Widhalm K., Dirisamer A., Lindemayr A., Kostner G.;
RT "Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100
RT defect by means of DNA analysis of LDL-receptor gene mutations.";
RL J. Inherit. Metab. Dis. 30:239-247(2007).
RN [88]
RP VARIANTS FHCL1 TYR-155; GLY-300; GLY-301; TRP-416 AND ASN-454.
RX PubMed=19318025; DOI=10.1016/j.clinbiochem.2009.01.017;
RA Alonso R., Defesche J.C., Tejedor D., Castillo S., Stef M., Mata N.,
RA Gomez-Enterria P., Martinez-Faedo C., Forga L., Mata P.;
RT "Genetic diagnosis of familial hypercholesterolemia using a DNA-array based
RT platform.";
RL Clin. Biochem. 42:899-903(2009).
RN [89]
RP VARIANTS FHCL1 PRO-254; TYR-356; TYR-358; THR-451 AND SER-826.
RX PubMed=19319977; DOI=10.1002/humu.21002;
RA Abifadel M., Rabes J.-P., Jambart S., Halaby G., Gannage-Yared M.-H.,
RA Sarkis A., Beaino G., Varret M., Salem N., Corbani S., Aydenian H.,
RA Junien C., Munnich A., Boileau C.;
RT "The molecular basis of familial hypercholesterolemia in Lebanon: spectrum
RT of LDLR mutations and role of PCSK9 as a modifier gene.";
RL Hum. Mutat. 30:E682-E691(2009).
RN [90]
RP VARIANTS HIS-139; LYS-201; SER-255; ASN-304 AND GLY-471.
RX PubMed=21418584; DOI=10.1186/1471-2350-12-40;
RA Al-Khateeb A., Zahri M.K., Mohamed M.S., Sasongko T.H., Ibrahim S.,
RA Yusof Z., Zilfalil B.A.;
RT "Analysis of sequence variations in low-density lipoprotein receptor gene
RT among Malaysian patients with familial hypercholesterolemia.";
RL BMC Med. Genet. 12:40-40(2011).
RN [91]
RP VARIANT FHCL1 PHE-329.
RX PubMed=22160468; DOI=10.1007/s11033-011-1314-0;
RA Walus-Miarka M., Sanak M., Idzior-Walus B., Miarka P., Witek P.,
RA Malecki M.T., Czarnecka D.;
RT "A novel mutation (Cys308Phe) of the LDL receptor gene in families from the
RT South-Eastern part of Poland.";
RL Mol. Biol. Rep. 39:5181-5186(2012).
RN [92]
RP VARIANTS FHCL1 TYR-160; ALA-168; LEU-177; TYR-184; GLY-221; GLN-228;
RP LYS-228; TRP-276; TYR-285; GLY-301; PHE-318; CYS-326; SER-343; TYR-368;
RP ASP-373; TRP-406; MET-429; ASN-492; ASP-549; HIS-564; HIS-574; TRP-595;
RP HIS-601; LEU-685; LEU-699; MET-797 AND GLN-814.
RX PubMed=24529145; DOI=10.1016/j.atherosclerosis.2013.12.028;
RA Santos P.C., Morgan A.C., Jannes C.E., Turolla L., Krieger J.E.,
RA Santos R.D., Pereira A.C.;
RT "Presence and type of low density lipoprotein receptor (LDLR) mutation
RT influences the lipid profile and response to lipid-lowering therapy in
RT Brazilian patients with heterozygous familial hypercholesterolemia.";
RL Atherosclerosis 233:206-210(2014).
RN [93]
RP CHARACTERIZATION OF VARIANTS FHCL1 ARG-116; ASN-168; ASN-172; GLY-300 AND
RP GLY-301, AND CHARACTERIZATION OF VARIANT TRP-257.
RX PubMed=25545329; DOI=10.1016/j.atherosclerosis.2014.12.026;
RA Etxebarria A., Benito-Vicente A., Stef M., Ostolaza H., Palacios L.,
RA Martin C.;
RT "Activity-associated effect of LDL receptor missense variants located in
RT the cysteine-rich repeats.";
RL Atherosclerosis 238:304-312(2015).
RN [94]
RP CHARACTERIZATION OF VARIANTS FHCL1 TYR-155; TRP-416; ASN-454; GLY-577 AND
RP LYS-825.
RX PubMed=25378237; DOI=10.1002/humu.22721;
RA Etxebarria A., Benito-Vicente A., Palacios L., Stef M., Cenarro A.,
RA Civeira F., Ostolaza H., Martin C.;
RT "Functional characterization and classification of frequent low-density
RT lipoprotein receptor variants.";
RL Hum. Mutat. 36:129-141(2015).
CC -!- FUNCTION: Binds LDL, the major cholesterol-carrying lipoprotein of
CC plasma, and transports it into cells by endocytosis. In order to be
CC internalized, the receptor-ligand complexes must first cluster into
CC clathrin-coated pits. {ECO:0000269|PubMed:3005267,
CC ECO:0000269|PubMed:6091915}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C
CC virus in hepatocytes, but not through a direct interaction with viral
CC proteins. {ECO:0000269|PubMed:10535997, ECO:0000269|PubMed:12615904}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Vesicular
CC stomatitis virus. {ECO:0000269|PubMed:23589850}.
CC -!- FUNCTION: (Microbial infection) In case of HIV-1 infection, may
CC function as a receptor for extracellular Tat in neurons, mediating its
CC internalization in uninfected cells. {ECO:0000269|PubMed:11100124}.
CC -!- SUBUNIT: Interacts (via NPXY motif) with DAB2 (via PID domain); the
CC interaction is impaired by tyrosine phosphorylation of the NPXY motif
CC (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID
CC domain) (PubMed:12221107, PubMed:22509010). Interacts with ARRB1
CC (PubMed:12944399). Interacts with SNX17 (PubMed:14739284). Interacts
CC with the full-length immature form of PCSK9 (via C-terminus)
CC (PubMed:17461796, PubMed:21149300). {ECO:0000250|UniProtKB:P35951,
CC ECO:0000269|PubMed:12221107, ECO:0000269|PubMed:12944399,
CC ECO:0000269|PubMed:14739284, ECO:0000269|PubMed:17461796,
CC ECO:0000269|PubMed:21149300, ECO:0000269|PubMed:22509010}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.difficile toxin TcdA,
CC suggesting that it may contribute to TcdA toxin entry into cells.
CC {ECO:0000269|PubMed:31160825}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vesicular stomatitis
CC virus glycoprotein. {ECO:0000269|PubMed:23589850}.
CC -!- SUBUNIT: (Microbial infection) May interact with HIV-1 Tat.
CC {ECO:0000269|PubMed:11100124}.
CC -!- INTERACTION:
CC P01130; P04114: APOB; NbExp=4; IntAct=EBI-988319, EBI-3926040;
CC P01130; P02649: APOE; NbExp=4; IntAct=EBI-988319, EBI-1222467;
CC P01130; P02749: APOH; NbExp=3; IntAct=EBI-988319, EBI-2114682;
CC P01130; P01130: LDLR; NbExp=3; IntAct=EBI-988319, EBI-988319;
CC P01130; P30533: LRPAP1; NbExp=3; IntAct=EBI-988319, EBI-715927;
CC P01130; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-988319, EBI-3923617;
CC P01130; Q8NBP7: PCSK9; NbExp=10; IntAct=EBI-988319, EBI-7539251;
CC P01130; Q8NBP7-1: PCSK9; NbExp=4; IntAct=EBI-988319, EBI-15656131;
CC P01130; Q08117-2: TLE5; NbExp=3; IntAct=EBI-988319, EBI-11741437;
CC P01130; D3ZAR1: Ldlrap1; Xeno; NbExp=3; IntAct=EBI-988319, EBI-9250714;
CC P01130; P0DTC2: S; Xeno; NbExp=4; IntAct=EBI-988319, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17461796,
CC ECO:0000269|PubMed:19520913}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P01131}. Membrane, clathrin-coated pit
CC {ECO:0000303|PubMed:6091915}. Golgi apparatus
CC {ECO:0000269|PubMed:17461796}. Early endosome
CC {ECO:0000269|PubMed:17461796}. Late endosome
CC {ECO:0000269|PubMed:17461796}. Lysosome {ECO:0000269|PubMed:17461796}.
CC Note=Rapidly endocytosed upon ligand binding.
CC {ECO:0000269|PubMed:3104336}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=P01130-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P01130-2; Sequence=VSP_043053, VSP_043054;
CC Name=3;
CC IsoId=P01130-3; Sequence=VSP_055014, VSP_055015;
CC Name=4;
CC IsoId=P01130-4; Sequence=VSP_043595;
CC Name=5;
CC IsoId=P01130-5; Sequence=VSP_045525;
CC Name=6;
CC IsoId=P01130-6; Sequence=VSP_047413;
CC -!- DOMAIN: The NPXY motif mediates the interaction with the clathrin
CC adapter DAB2 and with LDLRAP1 which are involved in receptor
CC internalization. A few residues outside the motif also play a role in
CC the interaction. {ECO:0000269|PubMed:22509010}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:12754519,
CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:3005267}.
CC -!- PTM: Ubiquitinated by MYLIP leading to degradation.
CC {ECO:0000269|PubMed:19520913}.
CC -!- DISEASE: Hypercholesterolemia, familial, 1 (FHCL1) [MIM:143890]: A form
CC of hypercholesterolemia, a disorder of lipoprotein metabolism
CC characterized by elevated serum low-density lipoprotein (LDL)
CC cholesterol levels, which result in excess deposition of cholesterol in
CC tissues and leads to xanthelasma, xanthomas, accelerated
CC atherosclerosis and increased risk of premature coronary heart disease.
CC FHCL1 inheritance is autosomal dominant. {ECO:0000269|PubMed:10090484,
CC ECO:0000269|PubMed:10206683, ECO:0000269|PubMed:10422803,
CC ECO:0000269|PubMed:10447263, ECO:0000269|PubMed:10532689,
CC ECO:0000269|PubMed:10660340, ECO:0000269|PubMed:10882754,
CC ECO:0000269|PubMed:10978268, ECO:0000269|PubMed:10980548,
CC ECO:0000269|PubMed:11298688, ECO:0000269|PubMed:11462246,
CC ECO:0000269|PubMed:1446662, ECO:0000269|PubMed:1464748,
CC ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910,
CC ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:19318025,
CC ECO:0000269|PubMed:19319977, ECO:0000269|PubMed:22160468,
CC ECO:0000269|PubMed:22509010, ECO:0000269|PubMed:2318961,
CC ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25378237,
CC ECO:0000269|PubMed:25545329, ECO:0000269|PubMed:2569482,
CC ECO:0000269|PubMed:2726768, ECO:0000269|PubMed:3263645,
CC ECO:0000269|PubMed:3955657, ECO:0000269|PubMed:7550239,
CC ECO:0000269|PubMed:7573037, ECO:0000269|PubMed:7583548,
CC ECO:0000269|PubMed:7635461, ECO:0000269|PubMed:7635482,
CC ECO:0000269|PubMed:7649546, ECO:0000269|PubMed:7649549,
CC ECO:0000269|PubMed:8168830, ECO:0000269|PubMed:8347689,
CC ECO:0000269|PubMed:8462973, ECO:0000269|PubMed:8664907,
CC ECO:0000269|PubMed:8740918, ECO:0000269|PubMed:9026534,
CC ECO:0000269|PubMed:9104431, ECO:0000269|PubMed:9143924,
CC ECO:0000269|PubMed:9254862, ECO:0000269|PubMed:9259195,
CC ECO:0000269|PubMed:9452094, ECO:0000269|PubMed:9452095,
CC ECO:0000269|PubMed:9452118, ECO:0000269|PubMed:9654205,
CC ECO:0000269|PubMed:9678702, ECO:0000269|PubMed:9852677,
CC ECO:0000269|Ref.72}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92646.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=LDLR; Note=LDLR mutation database;
CC URL="https://www.ucl.ac.uk/ldlr/LOVDv.1.1.0/index/";
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DR EMBL; L00352; AAA56833.1; -; Genomic_DNA.
DR EMBL; L00336; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00337; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00338; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00339; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00340; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00341; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00343; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00344; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00345; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00346; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00347; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00348; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00349; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00350; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L00351; AAA56833.1; JOINED; Genomic_DNA.
DR EMBL; L29401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY114155; AAM56036.1; -; mRNA.
DR EMBL; AK295612; BAG58495.1; -; mRNA.
DR EMBL; AK296312; BAG59010.1; -; mRNA.
DR EMBL; AK299038; BAG61112.1; -; mRNA.
DR EMBL; AK300313; BAG62065.1; -; mRNA.
DR EMBL; BT007361; AAP36025.1; -; mRNA.
DR EMBL; AY324609; AAP72971.1; -; Genomic_DNA.
DR EMBL; AB209409; BAD92646.1; ALT_INIT; mRNA.
DR EMBL; FJ525879; ACN81317.1; -; Genomic_DNA.
DR EMBL; AC011485; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84169.1; -; Genomic_DNA.
DR EMBL; BC014514; AAH14514.1; -; mRNA.
DR CCDS; CCDS12254.1; -. [P01130-1]
DR CCDS; CCDS56083.1; -. [P01130-2]
DR CCDS; CCDS56084.1; -. [P01130-3]
DR CCDS; CCDS56085.1; -. [P01130-4]
DR CCDS; CCDS58651.1; -. [P01130-5]
DR PIR; A01383; QRHULD.
DR RefSeq; NP_000518.1; NM_000527.4. [P01130-1]
DR RefSeq; NP_001182727.1; NM_001195798.1. [P01130-5]
DR RefSeq; NP_001182728.1; NM_001195799.1. [P01130-4]
DR RefSeq; NP_001182729.1; NM_001195800.1. [P01130-3]
DR RefSeq; NP_001182732.1; NM_001195803.1. [P01130-2]
DR PDB; 1AJJ; X-ray; 1.70 A; A=196-232.
DR PDB; 1D2J; NMR; -; A=233-272.
DR PDB; 1F5Y; NMR; -; A=22-104.
DR PDB; 1F8Z; NMR; -; A=234-272.
DR PDB; 1HJ7; NMR; -; A=314-393.
DR PDB; 1HZ8; NMR; -; A=314-395.
DR PDB; 1I0U; NMR; -; A=314-395.
DR PDB; 1IJQ; X-ray; 1.50 A; A/B=398-713.
DR PDB; 1LDL; NMR; -; A=20-67.
DR PDB; 1LDR; NMR; -; A=64-104.
DR PDB; 1N7D; X-ray; 3.70 A; A=22-720.
DR PDB; 1XFE; NMR; -; A=272-353.
DR PDB; 2FCW; X-ray; 1.26 A; B=107-186.
DR PDB; 2KRI; NMR; -; B=147-186.
DR PDB; 2LGP; NMR; -; A=144-235.
DR PDB; 2M7P; NMR; -; A=82-104.
DR PDB; 2MG9; NMR; -; A=314-339.
DR PDB; 2W2M; X-ray; 2.40 A; E=314-393.
DR PDB; 2W2N; X-ray; 2.30 A; E=314-393.
DR PDB; 2W2O; X-ray; 2.62 A; E=314-393.
DR PDB; 2W2P; X-ray; 2.62 A; E=314-393.
DR PDB; 2W2Q; X-ray; 2.33 A; E=314-393.
DR PDB; 3BPS; X-ray; 2.41 A; E=314-393.
DR PDB; 3GCW; X-ray; 2.70 A; E=314-393.
DR PDB; 3GCX; X-ray; 2.70 A; E=314-393.
DR PDB; 3M0C; X-ray; 7.01 A; C=4-788.
DR PDB; 3P5B; X-ray; 3.30 A; L=316-715.
DR PDB; 3P5C; X-ray; 4.20 A; L=276-715.
DR PDB; 3SO6; X-ray; 1.37 A; Q=819-832.
DR PDB; 4NE9; X-ray; 2.60 A; D=314-339.
DR PDB; 5OY9; X-ray; 3.60 A; D=108-144.
DR PDB; 5OYL; X-ray; 2.25 A; D=65-106.
DR PDBsum; 1AJJ; -.
DR PDBsum; 1D2J; -.
DR PDBsum; 1F5Y; -.
DR PDBsum; 1F8Z; -.
DR PDBsum; 1HJ7; -.
DR PDBsum; 1HZ8; -.
DR PDBsum; 1I0U; -.
DR PDBsum; 1IJQ; -.
DR PDBsum; 1LDL; -.
DR PDBsum; 1LDR; -.
DR PDBsum; 1N7D; -.
DR PDBsum; 1XFE; -.
DR PDBsum; 2FCW; -.
DR PDBsum; 2KRI; -.
DR PDBsum; 2LGP; -.
DR PDBsum; 2M7P; -.
DR PDBsum; 2MG9; -.
DR PDBsum; 2W2M; -.
DR PDBsum; 2W2N; -.
DR PDBsum; 2W2O; -.
DR PDBsum; 2W2P; -.
DR PDBsum; 2W2Q; -.
DR PDBsum; 3BPS; -.
DR PDBsum; 3GCW; -.
DR PDBsum; 3GCX; -.
DR PDBsum; 3M0C; -.
DR PDBsum; 3P5B; -.
DR PDBsum; 3P5C; -.
DR PDBsum; 3SO6; -.
DR PDBsum; 4NE9; -.
DR PDBsum; 5OY9; -.
DR PDBsum; 5OYL; -.
DR AlphaFoldDB; P01130; -.
DR BMRB; P01130; -.
DR SMR; P01130; -.
DR BioGRID; 110141; 450.
DR ComplexPortal; CPX-128; LDLR-PCSK9 complex.
DR DIP; DIP-29695N; -.
DR ELM; P01130; -.
DR IntAct; P01130; 48.
DR MINT; P01130; -.
DR STRING; 9606.ENSP00000454071; -.
DR BindingDB; P01130; -.
DR ChEMBL; CHEMBL3311; -.
DR DrugBank; DB14003; alpha-Tocopherol acetate.
DR DrugBank; DB00080; Daptomycin.
DR DrugBank; DB00707; Porfimer sodium.
DR DrugBank; DB11251; Tocopherol.
DR DrugBank; DB09270; Ubidecarenone.
DR GlyConnect; 343; 10 N-Linked glycans (4 sites), 4 O-Linked glycans.
DR GlyGen; P01130; 12 sites, 9 N-linked glycans (4 sites), 10 O-linked glycans (6 sites).
DR iPTMnet; P01130; -.
DR PhosphoSitePlus; P01130; -.
DR BioMuta; LDLR; -.
DR DMDM; 126073; -.
DR EPD; P01130; -.
DR jPOST; P01130; -.
DR MassIVE; P01130; -.
DR MaxQB; P01130; -.
DR PaxDb; P01130; -.
DR PeptideAtlas; P01130; -.
DR PRIDE; P01130; -.
DR ProteomicsDB; 40062; -.
DR ProteomicsDB; 40658; -.
DR ProteomicsDB; 51326; -. [P01130-1]
DR ProteomicsDB; 51327; -. [P01130-2]
DR ProteomicsDB; 51328; -. [P01130-3]
DR ProteomicsDB; 51329; -. [P01130-4]
DR Antibodypedia; 2424; 965 antibodies from 43 providers.
DR DNASU; 3949; -.
DR Ensembl; ENST00000455727.6; ENSP00000397829.2; ENSG00000130164.14. [P01130-3]
DR Ensembl; ENST00000535915.5; ENSP00000440520.1; ENSG00000130164.14. [P01130-4]
DR Ensembl; ENST00000545707.5; ENSP00000437639.1; ENSG00000130164.14. [P01130-2]
DR Ensembl; ENST00000558013.5; ENSP00000453346.1; ENSG00000130164.14. [P01130-5]
DR Ensembl; ENST00000558518.6; ENSP00000454071.1; ENSG00000130164.14. [P01130-1]
DR GeneID; 3949; -.
DR KEGG; hsa:3949; -.
DR MANE-Select; ENST00000558518.6; ENSP00000454071.1; NM_000527.5; NP_000518.1.
DR UCSC; uc002mqk.5; human. [P01130-1]
DR CTD; 3949; -.
DR DisGeNET; 3949; -.
DR GeneCards; LDLR; -.
DR GeneReviews; LDLR; -.
DR HGNC; HGNC:6547; LDLR.
DR HPA; ENSG00000130164; Tissue enhanced (adrenal).
DR MalaCards; LDLR; -.
DR MIM; 143890; phenotype.
DR MIM; 606945; gene.
DR neXtProt; NX_P01130; -.
DR OpenTargets; ENSG00000130164; -.
DR Orphanet; 391665; Homozygous familial hypercholesterolemia.
DR Orphanet; 406; NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia.
DR PharmGKB; PA227; -.
DR VEuPathDB; HostDB:ENSG00000130164; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000161046; -.
DR HOGENOM; CLU_008163_4_0_1; -.
DR InParanoid; P01130; -.
DR OMA; IMNEAIF; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; P01130; -.
DR TreeFam; TF351700; -.
DR PathwayCommons; P01130; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-8964026; Chylomicron clearance.
DR Reactome; R-HSA-8964038; LDL clearance.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; P01130; -.
DR SIGNOR; P01130; -.
DR BioGRID-ORCS; 3949; 53 hits in 1092 CRISPR screens.
DR ChiTaRS; LDLR; human.
DR EvolutionaryTrace; P01130; -.
DR GeneWiki; LDL_receptor; -.
DR GenomeRNAi; 3949; -.
DR Pharos; P01130; Tchem.
DR PRO; PR:P01130; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P01130; protein.
DR Bgee; ENSG00000130164; Expressed in adrenal tissue and 194 other tissues.
DR ExpressionAtlas; P01130; baseline and differential.
DR Genevisible; P01130; HS.
DR GO; GO:0045177; C:apical part of cell; ISS:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:BHF-UCL.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0034362; C:low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:1990666; C:PCSK9-LDLR complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0036477; C:somatodendritic compartment; IEA:Ensembl.
DR GO; GO:0097443; C:sorting endosome; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; ISS:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0032050; F:clathrin heavy chain binding; TAS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0071813; F:lipoprotein particle binding; IBA:GO_Central.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; IMP:BHF-UCL.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IDA:BHF-UCL.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; IDA:BHF-UCL.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; ISS:ARUK-UCL.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IMP:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0070508; P:cholesterol import; IMP:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030301; P:cholesterol transport; IMP:HGNC-UCL.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0034384; P:high-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IMP:HGNC-UCL.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IGI:ARUK-UCL.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IMP:BHF-UCL.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:ARUK-UCL.
DR GO; GO:0061889; P:negative regulation of astrocyte activation; ISS:ARUK-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IDA:ComplexPortal.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:ARUK-UCL.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; ISS:ARUK-UCL.
DR GO; GO:0001920; P:negative regulation of receptor recycling; IDA:ComplexPortal.
DR GO; GO:0006909; P:phagocytosis; ISS:ARUK-UCL.
DR GO; GO:0015914; P:phospholipid transport; ISS:BHF-UCL.
DR GO; GO:0034381; P:plasma lipoprotein particle clearance; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; ISS:ARUK-UCL.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:ARUK-UCL.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IMP:BHF-UCL.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0010899; P:regulation of phosphatidylcholine catabolic process; ISS:BHF-UCL.
DR GO; GO:0051246; P:regulation of protein metabolic process; IGI:ARUK-UCL.
DR GO; GO:0061771; P:response to caloric restriction; IGI:ARUK-UCL.
DR CDD; cd00112; LDLa; 7.
DR DisProt; DP01396; -.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 4.10.400.10; -; 6.
DR IDEAL; IID00646; -.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00057; Ldl_recept_a; 7.
DR Pfam; PF00058; Ldl_recept_b; 5.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00192; LDLa; 7.
DR SMART; SM00135; LY; 5.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57424; SSF57424; 7.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS01209; LDLRA_1; 7.
DR PROSITE; PS50068; LDLRA_2; 7.
DR PROSITE; PS51120; LDLRB; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cholesterol metabolism;
KW Coated pit; Direct protein sequencing; Disease variant; Disulfide bond;
KW EGF-like domain; Endocytosis; Endosome; Glycoprotein; Golgi apparatus;
KW Host cell receptor for virus entry; Host-virus interaction; LDL;
KW Lipid metabolism; Lipid transport; Lysosome; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT CHAIN 22..860
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000017312"
FT TOPO_DOM 22..788
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT TRANSMEM 789..810
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 811..860
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22509010"
FT DOMAIN 25..65
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 66..106
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 107..145
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 146..186
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 195..233
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 234..272
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 274..313
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 314..353
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 354..393
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 397..438
FT /note="LDL-receptor class B 1"
FT REPEAT 439..485
FT /note="LDL-receptor class B 2"
FT REPEAT 486..528
FT /note="LDL-receptor class B 3"
FT REPEAT 529..572
FT /note="LDL-receptor class B 4"
FT REPEAT 573..615
FT /note="LDL-receptor class B 5"
FT REPEAT 616..658
FT /note="LDL-receptor class B 6"
FT DOMAIN 663..712
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 721..768
FT /note="Clustered O-linked oligosaccharides"
FT REGION 734..755
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 811..860
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000269|PubMed:19520913"
FT MOTIF 823..828
FT /note="NPXY motif"
FT /evidence="ECO:0000269|PubMed:22509010"
FT COMPBIAS 734..749
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 724
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35952"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19520913"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19520913"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT DISULFID 27..39
FT DISULFID 34..52
FT DISULFID 46..63
FT DISULFID 68..82
FT DISULFID 75..95
FT DISULFID 89..104
FT DISULFID 109..121
FT /evidence="ECO:0000250"
FT DISULFID 116..134
FT DISULFID 128..143
FT DISULFID 148..160
FT DISULFID 155..173
FT DISULFID 167..184
FT DISULFID 197..209
FT DISULFID 204..222
FT DISULFID 216..231
FT DISULFID 236..248
FT DISULFID 243..261
FT DISULFID 255..270
FT DISULFID 276..289
FT DISULFID 284..302
FT DISULFID 296..313
FT DISULFID 318..329
FT DISULFID 325..338
FT DISULFID 340..352
FT DISULFID 358..368
FT DISULFID 364..377
FT DISULFID 379..392
FT DISULFID 667..681
FT DISULFID 677..696
FT DISULFID 698..711
FT VAR_SEQ 35..155
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047413"
FT VAR_SEQ 64..105
FT /note="LSVTCKSGDFSCGGRVNRCIPQFWRCDGQVDCDNGSDEQGCP -> S (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043595"
FT VAR_SEQ 105..272
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055014"
FT VAR_SEQ 106..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043053"
FT VAR_SEQ 273
FT /note="V -> L (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055015"
FT VAR_SEQ 663..713
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043054"
FT VAR_SEQ 850..851
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_045525"
FT VARIANT 2
FT /note="G -> R (in dbSNP:rs5931)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011862"
FT VARIANT 27
FT /note="C -> W (in FHCL1; San Francisco; dbSNP:rs2228671)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005304"
FT VARIANT 46
FT /note="C -> S (in FHCL1; Japanese patient;
FT dbSNP:rs121908041)"
FT /evidence="ECO:0000269|PubMed:11298688"
FT /id="VAR_013949"
FT VARIANT 47..48
FT /note="Missing (in FHCL1; Cape Town-1; retards receptor
FT transport from the endoplasmic reticulum to the cell
FT surface)"
FT /evidence="ECO:0000269|PubMed:10882754,
FT ECO:0000269|PubMed:3263645"
FT /id="VAR_005305"
FT VARIANT 50
FT /note="A -> S (in FHCL1; German patient;
FT dbSNP:rs137853960)"
FT /evidence="ECO:0000269|PubMed:10090484"
FT /id="VAR_007979"
FT VARIANT 50
FT /note="A -> T (in FHCL1; unknown pathological significance;
FT dbSNP:rs137853960)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072827"
FT VARIANT 52
FT /note="C -> Y (in Paris-4; dbSNP:rs879254418)"
FT /id="VAR_005306"
FT VARIANT 56
FT /note="S -> P (in FHCL1; dbSNP:rs878854026)"
FT /evidence="ECO:0000269|PubMed:9104431"
FT /id="VAR_007980"
FT VARIANT 78
FT /note="R -> C (in FHCL1; dbSNP:rs370860696)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005307"
FT VARIANT 87
FT /note="W -> G (in FHCL1; French Canadian-4;
FT dbSNP:rs121908025)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:2318961, ECO:0000269|PubMed:9259195"
FT /id="VAR_005308"
FT VARIANT 89
FT /note="C -> Y (in FHCL1; dbSNP:rs875989894)"
FT /evidence="ECO:0000269|PubMed:17142622,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005309"
FT VARIANT 90
FT /note="D -> G (in FHCL1; London-4; dbSNP:rs771019366)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005310"
FT VARIANT 90
FT /note="D -> N (in FHCL1; dbSNP:rs749038326)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005311"
FT VARIANT 90
FT /note="D -> Y (in FHCL1; Durban-1; dbSNP:rs749038326)"
FT /evidence="ECO:0000269|PubMed:8347689"
FT /id="VAR_005312"
FT VARIANT 92
FT /note="Q -> E (in FHCL1; Spanish patient;
FT dbSNP:rs774467219)"
FT /evidence="ECO:0000269|PubMed:10206683"
FT /id="VAR_005313"
FT VARIANT 95
FT /note="C -> G (in FHCL1; Spanish patient;
FT dbSNP:rs879254456)"
FT /evidence="ECO:0000269|PubMed:10206683"
FT /id="VAR_005314"
FT VARIANT 101
FT /note="E -> K (in FHCL1; Lancashire; 6% of American
FT English; dbSNP:rs144172724)"
FT /evidence="ECO:0000269|PubMed:17142622,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005315"
FT VARIANT 105
FT /note="P -> S (in dbSNP:rs13306510)"
FT /id="VAR_059375"
FT VARIANT 109
FT /note="C -> R (in Munster-1; dbSNP:rs140807148)"
FT /id="VAR_005316"
FT VARIANT 116
FT /note="C -> R (in FHCL1; does not affect receptor
FT expression at the cell surface; results in reduced LDL
FT binding; results in reduced LDL uptake and internalization;
FT dbSNP:rs879254482)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:25545329"
FT /id="VAR_005317"
FT VARIANT 134
FT /note="C -> F (in FHCL1; dbSNP:rs879254514)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062371"
FT VARIANT 134
FT /note="C -> W (in FHCL1; dbSNP:rs879254515)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062372"
FT VARIANT 139
FT /note="D -> H (found in a patient with
FT hypercholesterolemia; dbSNP:rs879254517)"
FT /evidence="ECO:0000269|PubMed:21418584"
FT /id="VAR_065780"
FT VARIANT 140
FT /note="E -> K (in FHCL1; Philippines/Durban-2/Japan;
FT dbSNP:rs748944640)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:8347689"
FT /id="VAR_005318"
FT VARIANT 143
FT /note="C -> R (in FHCL1; dbSNP:rs875989901)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072828"
FT VARIANT 148
FT /note="C -> Y (in FHCL1; dbSNP:rs879254526)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072829"
FT VARIANT 155
FT /note="C -> G (in Germany; dbSNP:rs879254535)"
FT /id="VAR_005319"
FT VARIANT 155
FT /note="C -> Y (in FHCL1; results in defective LDL binding;
FT does not affect receptor expression at the cell surface;
FT dbSNP:rs879254536)"
FT /evidence="ECO:0000269|PubMed:19318025,
FT ECO:0000269|PubMed:25378237"
FT /id="VAR_072830"
FT VARIANT 160
FT /note="C -> Y (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254541)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005320"
FT VARIANT 168
FT /note="D -> A (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254549)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072831"
FT VARIANT 168
FT /note="D -> H (in FHCL1; Sephardic/Safed; 10% of the
FT Sephardic Jews; dbSNP:rs200727689)"
FT /evidence="ECO:0000269|PubMed:8462973"
FT /id="VAR_005321"
FT VARIANT 168
FT /note="D -> N (in FHCL1; does not affect receptor
FT expression at the cell surface; results in reduced LDL
FT binding; results in reduced LDL uptake and internalization;
FT dbSNP:rs200727689)"
FT /evidence="ECO:0000269|PubMed:25545329,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005322"
FT VARIANT 168
FT /note="D -> Y (in FHCL1; dbSNP:rs200727689)"
FT /evidence="ECO:0000269|PubMed:8740918"
FT /id="VAR_005323"
FT VARIANT 172
FT /note="D -> H (may contribute to familial
FT hypercholesterolemia; dbSNP:rs879254554)"
FT /evidence="ECO:0000269|PubMed:10882754"
FT /id="VAR_013950"
FT VARIANT 172
FT /note="D -> N (in FHCL1; does not affect receptor
FT expression at the cell surface; results in reduced LDL
FT binding; results in reduced LDL uptake and internalization;
FT dbSNP:rs879254554)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:25545329"
FT /id="VAR_072832"
FT VARIANT 173
FT /note="C -> R (in Greece-1; dbSNP:rs879254558)"
FT /id="VAR_005324"
FT VARIANT 173
FT /note="C -> W (in FHCL1; dbSNP:rs769318035)"
FT /evidence="ECO:0000269|PubMed:9452094"
FT /id="VAR_005325"
FT VARIANT 175
FT /note="D -> N (in FHCL1; Afrikaner-3; 5-10% of Afrikaners;
FT dbSNP:rs121908033)"
FT /evidence="ECO:0000269|PubMed:2569482"
FT /id="VAR_005326"
FT VARIANT 175
FT /note="D -> Y (in FHCL1; dbSNP:rs121908033)"
FT /evidence="ECO:0000269|PubMed:9104431"
FT /id="VAR_007981"
FT VARIANT 177
FT /note="S -> L (in FHCL1; Puerto Rico; dbSNP:rs121908026)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:9259195,
FT ECO:0000269|PubMed:9654205"
FT /id="VAR_005327"
FT VARIANT 184
FT /note="C -> W (in FHCL1; dbSNP:rs879254571)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072833"
FT VARIANT 184
FT /note="C -> Y (in FHCL1; Glasco; dbSNP:rs121908039)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:9678702"
FT /id="VAR_013951"
FT VARIANT 197
FT /note="C -> F (in Shreveport; dbSNP:rs376459828)"
FT /id="VAR_005328"
FT VARIANT 197
FT /note="C -> R (in FHCL1; British patient;
FT dbSNP:rs730882085)"
FT /evidence="ECO:0000269|PubMed:9026534"
FT /id="VAR_005330"
FT VARIANT 197
FT /note="C -> Y (in El Salvador-1; dbSNP:rs376459828)"
FT /id="VAR_005329"
FT VARIANT 201
FT /note="E -> K (found in a patient with
FT hypercholesterolemia; dbSNP:rs879254589)"
FT /evidence="ECO:0000269|PubMed:21418584"
FT /id="VAR_065781"
FT VARIANT 211
FT /note="H -> L (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254603)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072834"
FT VARIANT 218
FT /note="Missing (in FHCL1; Piscataway/Lithuania)"
FT /evidence="ECO:0000269|PubMed:17142622,
FT ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:9654205"
FT /id="VAR_005331"
FT VARIANT 221
FT /note="D -> G (in FHCL1; Padova; dbSNP:rs373822756)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910,
FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:7649546,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005332"
FT VARIANT 221
FT /note="D -> N (in FHCL1; German patient;
FT dbSNP:rs875989906)"
FT /evidence="ECO:0000269|PubMed:10090484,
FT ECO:0000269|PubMed:17142622"
FT /id="VAR_007982"
FT VARIANT 221
FT /note="D -> Y (in FHCL1; Cologne patient;
FT dbSNP:rs875989906)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:7649546"
FT /id="VAR_005333"
FT VARIANT 222
FT /note="C -> Y (in FHCL1; dbSNP:rs730882086)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062373"
FT VARIANT 224
FT /note="D -> G (in Italy-2; dbSNP:rs879254630)"
FT /id="VAR_005335"
FT VARIANT 224
FT /note="D -> N (in Portugal; dbSNP:rs387906303)"
FT /id="VAR_005334"
FT VARIANT 224
FT /note="D -> V (in FHCL1; Cologne patient;
FT dbSNP:rs879254630)"
FT /evidence="ECO:0000269|PubMed:7649546"
FT /id="VAR_005336"
FT VARIANT 226
FT /note="S -> P (in Miami-1; dbSNP:rs879254635)"
FT /id="VAR_005337"
FT VARIANT 227
FT /note="D -> E (in FHCL1; Afrikaner-1/Maine; 65-70% of
FT Afrikaner Americans; dbSNP:rs121908028)"
FT /evidence="ECO:0000269|PubMed:2569482,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005338"
FT VARIANT 228
FT /note="E -> CK (in Chieti-3)"
FT /evidence="ECO:0000269|PubMed:10660340"
FT /id="VAR_005339"
FT VARIANT 228
FT /note="E -> K (in FHCL1; French Canadian-3/Mexico; 2% of
FT French Canadians; dbSNP:rs121908029)"
FT /evidence="ECO:0000269|PubMed:2318961,
FT ECO:0000269|PubMed:24529145"
FT /id="VAR_005341"
FT VARIANT 228
FT /note="E -> Q (in FHCL1; Tulsa-2; dbSNP:rs121908029)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_005340"
FT VARIANT 231
FT /note="C -> G (in FHCL1; Norwegian patient;
FT dbSNP:rs746091400)"
FT /evidence="ECO:0000269|PubMed:8664907"
FT /id="VAR_005342"
FT VARIANT 240
FT /note="E -> K (in Charlotte; dbSNP:rs768563000)"
FT /id="VAR_005343"
FT VARIANT 243
FT /note="C -> R (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254659)"
FT /evidence="ECO:0000269|PubMed:10532689"
FT /id="VAR_072835"
FT VARIANT 248
FT /note="C -> F (in Bretagne-1; dbSNP:rs879254663)"
FT /id="VAR_005344"
FT VARIANT 248
FT /note="C -> Y (in FHCL1; British patient;
FT dbSNP:rs879254663)"
FT /evidence="ECO:0000269|PubMed:9026534"
FT /id="VAR_005345"
FT VARIANT 253
FT /note="R -> W (may contribute to familial
FT hypercholesterolemia; dbSNP:rs150673992)"
FT /evidence="ECO:0000269|PubMed:10882754"
FT /id="VAR_013952"
FT VARIANT 254
FT /note="Q -> P (in FHCL1; dbSNP:rs879254667)"
FT /evidence="ECO:0000269|PubMed:10978268,
FT ECO:0000269|PubMed:19319977"
FT /id="VAR_062374"
FT VARIANT 255
FT /note="C -> S (found in a patient with
FT hypercholesterolemia; dbSNP:rs879254668)"
FT /evidence="ECO:0000269|PubMed:21418584"
FT /id="VAR_065782"
FT VARIANT 256
FT /note="D -> G (in Nevers; dbSNP:rs879254670)"
FT /id="VAR_005346"
FT VARIANT 257
FT /note="R -> W (does not affect receptor expression at the
FT cell surface; does not affect LDL binding; does not affect
FT LDL uptake and internalization; dbSNP:rs200990725)"
FT /evidence="ECO:0000269|PubMed:11462246,
FT ECO:0000269|PubMed:25545329"
FT /id="VAR_072836"
FT VARIANT 261
FT /note="C -> F (in FHCL1; rare mutation; strongly reduced
FT receptor activity; dbSNP:rs121908040)"
FT /evidence="ECO:0000269|PubMed:10422803"
FT /id="VAR_013953"
FT VARIANT 266
FT /note="D -> E (in FHCL1; Cincinnati-1; unknown pathological
FT significance; dbSNP:rs139043155)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_005347"
FT VARIANT 270
FT /note="C -> Y (in Miami-2; dbSNP:rs879254683)"
FT /id="VAR_005348"
FT VARIANT 276
FT /note="C -> R (in FHCL1; dbSNP:rs879254692)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062375"
FT VARIANT 276
FT /note="C -> W (in FHCL1; unknown pathological significance;
FT dbSNP:rs146651743)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072837"
FT VARIANT 276
FT /note="C -> Y (in FHCL1; Syrian patient;
FT dbSNP:rs730882089)"
FT /evidence="ECO:0000269|Ref.72"
FT /id="VAR_005349"
FT VARIANT 277
FT /note="E -> K (in FHCL1; patients from Sweden and La
FT Havana; unknown pathological significance;
FT dbSNP:rs148698650)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:7635461,
FT ECO:0000269|PubMed:7649549"
FT /id="VAR_005350"
FT VARIANT 285
FT /note="H -> Y (in FHCL1; unknown pathological significance;
FT dbSNP:rs730882091)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072838"
FT VARIANT 286
FT /note="S -> R (in FHCL1; Greece-2; unknown pathological
FT significance; dbSNP:rs140241383)"
FT /evidence="ECO:0000269|PubMed:17347910,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005351"
FT VARIANT 288
FT /note="E -> K (in FHCL1; German patient;
FT dbSNP:rs368657165)"
FT /evidence="ECO:0000269|PubMed:10090484"
FT /id="VAR_007983"
FT VARIANT 300
FT /note="R -> G (in FHCL1; does not affect receptor
FT expression at the cell surface; results in reduced LDL
FT binding; results in reduced LDL uptake and internalization;
FT dbSNP:rs767618089)"
FT /evidence="ECO:0000269|PubMed:19318025,
FT ECO:0000269|PubMed:25545329"
FT /id="VAR_072839"
FT VARIANT 301
FT /note="D -> A (in FHCL1; Greek patient; dbSNP:rs879254714)"
FT /evidence="ECO:0000269|PubMed:9026534"
FT /id="VAR_005352"
FT VARIANT 301
FT /note="D -> G (in FHCL1; does not affect receptor
FT expression at the cell surface; results in reduced LDL
FT binding; results in reduced LDL uptake and internalization;
FT dbSNP:rs879254714)"
FT /evidence="ECO:0000269|PubMed:19318025,
FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25545329"
FT /id="VAR_072840"
FT VARIANT 302
FT /note="C -> W (in FHCL1; Iraki patient; dbSNP:rs879254716)"
FT /evidence="ECO:0000269|PubMed:9026534"
FT /id="VAR_005354"
FT VARIANT 302
FT /note="C -> Y (in FHCL1; Spanish patient;
FT dbSNP:rs879254715)"
FT /evidence="ECO:0000269|PubMed:10206683"
FT /id="VAR_005353"
FT VARIANT 304
FT /note="D -> E (in Baltimore-1; dbSNP:rs875989909)"
FT /id="VAR_005356"
FT VARIANT 304
FT /note="D -> N (in Denver-2; dbSNP:rs121908030)"
FT /evidence="ECO:0000269|PubMed:21418584"
FT /id="VAR_005355"
FT VARIANT 306
FT /note="S -> L (in FHCL1; Amsterdam; unknown pathological
FT significance; dbSNP:rs11547917)"
FT /evidence="ECO:0000269|PubMed:10532689"
FT /id="VAR_005357"
FT VARIANT 313
FT /note="C -> Y (in FHCL1; dbSNP:rs875989911 and
FT dbSNP:rs875989910)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005358"
FT VARIANT 314
FT /note="G -> R (in FHCL1; unknown pathological significance;
FT dbSNP:rs72658858)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072841"
FT VARIANT 318
FT /note="C -> F (in FHCL1; Trieste; dbSNP:rs879254739)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:8168830"
FT /id="VAR_005360"
FT VARIANT 318
FT /note="C -> R (in FHCL1; dbSNP:rs879254738)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062376"
FT VARIANT 318
FT /note="C -> Y (in Mexico-1; leads to a defect in the
FT intracellular transport of the receptor;
FT dbSNP:rs879254739)"
FT /id="VAR_005359"
FT VARIANT 326
FT /note="S -> C (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254747)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072842"
FT VARIANT 327
FT /note="H -> Y (in FHCL1; dbSNP:rs747507019)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005361"
FT VARIANT 329
FT /note="C -> F (in FHCL1; dbSNP:rs761954844)"
FT /evidence="ECO:0000269|PubMed:22160468"
FT /id="VAR_067196"
FT VARIANT 329
FT /note="C -> Y (in FHCL1; Chinese patient;
FT dbSNP:rs761954844)"
FT /evidence="ECO:0000269|PubMed:9452118"
FT /id="VAR_005362"
FT VARIANT 335
FT /note="G -> S (in Paris-6; dbSNP:rs544453230)"
FT /id="VAR_005363"
FT VARIANT 338
FT /note="C -> S (in FHCL1; Japanese patients;
FT dbSNP:rs879254753)"
FT /evidence="ECO:0000269|PubMed:10447263,
FT ECO:0000269|PubMed:7583548"
FT /id="VAR_005364"
FT VARIANT 342
FT /note="D -> E (in New York-1; dbSNP:rs780563386)"
FT /id="VAR_005365"
FT VARIANT 342
FT /note="D -> N (in FHCL1; unknown pathological significance;
FT dbSNP:rs139361635)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005366"
FT VARIANT 343
FT /note="G -> S (in FHCL1; Picardie; unknown pathological
FT significance; dbSNP:rs730882096)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_005367"
FT VARIANT 350
FT /note="R -> P (in FHCL1; dbSNP:rs875989914)"
FT /evidence="ECO:0000269|PubMed:9026534,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005368"
FT VARIANT 352
FT /note="C -> R (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254769)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072843"
FT VARIANT 352
FT /note="C -> Y (in Mexico-2; dbSNP:rs193922566)"
FT /id="VAR_005369"
FT VARIANT 354
FT /note="D -> G (in Munster-2; dbSNP:rs755449669)"
FT /id="VAR_005370"
FT VARIANT 354
FT /note="D -> V (in Oklahoma; dbSNP:rs755449669)"
FT /id="VAR_005371"
FT VARIANT 356
FT /note="D -> Y (in FHCL1; dbSNP:rs767767730)"
FT /evidence="ECO:0000269|PubMed:19319977,
FT ECO:0000269|PubMed:9104431"
FT /id="VAR_007984"
FT VARIANT 357
FT /note="E -> K (in Paris-7; dbSNP:rs879254781)"
FT /id="VAR_005372"
FT VARIANT 358
FT /note="C -> Y (in FHCL1; dbSNP:rs875989915)"
FT /evidence="ECO:0000269|PubMed:17142622,
FT ECO:0000269|PubMed:19319977"
FT /id="VAR_062377"
FT VARIANT 364
FT /note="C -> R (in Mexico-3; dbSNP:rs879254787)"
FT /id="VAR_005373"
FT VARIANT 366
FT /note="Q -> R (in FHCL1; dbSNP:rs746982741)"
FT /evidence="ECO:0000269|PubMed:8740918"
FT /id="VAR_007985"
FT VARIANT 368
FT /note="C -> R (in FHCL1; French Canadian patient;
FT dbSNP:rs879254791)"
FT /evidence="ECO:0000269|PubMed:9452094"
FT /id="VAR_005374"
FT VARIANT 368
FT /note="C -> Y (in FHCL1; unknown pathological significance;
FT dbSNP:rs768430352)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072844"
FT VARIANT 370
FT /note="N -> T (in FHCL1; dbSNP:rs879254792)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062378"
FT VARIANT 373
FT /note="G -> D (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254797)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072845"
FT VARIANT 379
FT /note="C -> R (in Naples-1; dbSNP:rs879254803)"
FT /id="VAR_005375"
FT VARIANT 379
FT /note="C -> Y (in FHCL1; dbSNP:rs879254804)"
FT /evidence="ECO:0000269|PubMed:9852677"
FT /id="VAR_007986"
FT VARIANT 391
FT /note="A -> T (in dbSNP:rs11669576)"
FT /id="VAR_024519"
FT VARIANT 399
FT /note="A -> D (in FHCL1; dbSNP:rs875989918)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005376"
FT VARIANT 401
FT /note="L -> H (in Pori; dbSNP:rs121908038)"
FT /evidence="ECO:0000269|PubMed:7573037"
FT /id="VAR_005377"
FT VARIANT 401
FT /note="L -> V (in FHCL1; dbSNP:rs146200173)"
FT /evidence="ECO:0000269|PubMed:9104431"
FT /id="VAR_007987"
FT VARIANT 403
FT /note="F -> L (in FHCL1; Japanese patient;
FT dbSNP:rs879254831)"
FT /evidence="ECO:0000269|PubMed:10447263"
FT /id="VAR_008995"
FT VARIANT 404
FT /note="T -> P (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254834)"
FT /evidence="ECO:0000269|PubMed:10532689"
FT /id="VAR_072846"
FT VARIANT 406
FT /note="R -> Q (may contribute to familial
FT hypercholesterolemia; dbSNP:rs552422789)"
FT /evidence="ECO:0000269|PubMed:10882754"
FT /id="VAR_013954"
FT VARIANT 406
FT /note="R -> W (in FHCL1; unknown pathological significance;
FT dbSNP:rs121908043)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072847"
FT VARIANT 408
FT /note="E -> K (in FHCL1; Algeria-1; unknown pathological
FT significance; dbSNP:rs137943601)"
FT /evidence="ECO:0000269|PubMed:10882754,
FT ECO:0000269|PubMed:17347910"
FT /id="VAR_005378"
FT VARIANT 414
FT /note="L -> R (in FHCL1; Chinese patient;
FT dbSNP:rs748554592)"
FT /evidence="ECO:0000269|PubMed:9452118"
FT /id="VAR_005379"
FT VARIANT 415
FT /note="D -> G (in FHCL1; dbSNP:rs879254845)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062379"
FT VARIANT 416
FT /note="R -> Q (in FHCL1; German patient;
FT dbSNP:rs773658037)"
FT /evidence="ECO:0000269|PubMed:9452095"
FT /id="VAR_005380"
FT VARIANT 416
FT /note="R -> W (in FHCL1; results in reduced receptor
FT expression at the cell surface due to defective receptor
FT recycling; dbSNP:rs570942190)"
FT /evidence="ECO:0000269|PubMed:19318025,
FT ECO:0000269|PubMed:25378237, ECO:0000269|PubMed:9104431,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005381"
FT VARIANT 423
FT /note="I -> T (in FHCL1; Swedish patient;
FT dbSNP:rs879254849)"
FT /evidence="ECO:0000269|PubMed:7635461"
FT /id="VAR_005382"
FT VARIANT 429
FT /note="V -> M (in FHCL1; Afrikaner-2; 20-30% of Afrikaners
FT and 2% of FHCL1 Dutch; dbSNP:rs28942078)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:2569482, ECO:0000269|PubMed:7649549,
FT ECO:0000269|PubMed:9452095, ECO:0000269|PubMed:9452118"
FT /id="VAR_005383"
FT VARIANT 431
FT /note="A -> T (in FHCL1; Algeria-2; unknown pathological
FT significance; dbSNP:rs28942079)"
FT /evidence="ECO:0000269|PubMed:10447263,
FT ECO:0000269|PubMed:17347910"
FT /id="VAR_005384"
FT VARIANT 432
FT /note="L -> V (in FHCL1; German patient;
FT dbSNP:rs730882100)"
FT /evidence="ECO:0000269|PubMed:10090484"
FT /id="VAR_007988"
FT VARIANT 433
FT /note="D -> H (in FHCL1; Osaka-3; dbSNP:rs121908036)"
FT /evidence="ECO:0000269|PubMed:1446662"
FT /id="VAR_005385"
FT VARIANT 434
FT /note="T -> K (in FHCL1; Algeria-3; unknown pathological
FT significance; dbSNP:rs745343524)"
FT /evidence="ECO:0000269|PubMed:10206683"
FT /id="VAR_005386"
FT VARIANT 441
FT /note="I -> M (in Rouen; dbSNP:rs5933)"
FT /id="VAR_005388"
FT VARIANT 441
FT /note="I -> N (in Russia-1; dbSNP:rs879254862)"
FT /id="VAR_005387"
FT VARIANT 442
FT /note="Y -> H (in FHCL1; unknown pathological significance;
FT dbSNP:rs879254863)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072848"
FT VARIANT 443
FT /note="W -> C (in North Platt; dbSNP:rs879254867)"
FT /id="VAR_005389"
FT VARIANT 451
FT /note="I -> T (in FHCL1; dbSNP:rs879254874)"
FT /evidence="ECO:0000269|PubMed:10980548,
FT ECO:0000269|PubMed:19319977"
FT /id="VAR_062380"
FT VARIANT 454
FT /note="T -> N (in FHCL1; results in reduced receptor
FT expression at the cell surface due to defective receptor
FT recycling; dbSNP:rs879254879)"
FT /evidence="ECO:0000269|PubMed:19318025,
FT ECO:0000269|PubMed:25378237"
FT /id="VAR_072849"
FT VARIANT 468
FT /note="V -> I (in dbSNP:rs5932)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011863"
FT VARIANT 471
FT /note="R -> G (found in a patient with
FT hypercholesterolemia; dbSNP:rs879254891)"
FT /evidence="ECO:0000269|PubMed:21418584"
FT /id="VAR_065783"
FT VARIANT 478
FT /note="G -> R (in New York-2; dbSNP:rs144614838)"
FT /id="VAR_005390"
FT VARIANT 479
FT /note="L -> P (in FHCL1; dbSNP:rs879254900)"
FT /evidence="ECO:0000269|PubMed:17142622"
FT /id="VAR_062381"
FT VARIANT 482
FT /note="D -> H (in FHCL1; dbSNP:rs139624145)"
FT /evidence="ECO:0000269|PubMed:17142622,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005391"
FT VARIANT 483
FT /note="W -> R (in FHCL1; dbSNP:rs879254905)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005392"
FT VARIANT 485
FT /note="H -> R (in Milan; dbSNP:rs879254906)"
FT /id="VAR_005394"
FT VARIANT 487
FT /note="Missing (in FHCL1; Norwegian patient)"
FT /evidence="ECO:0000269|PubMed:7635482"
FT /id="VAR_005393"
FT VARIANT 492
FT /note="D -> N (in FHCL1; unknown pathological significance;
FT dbSNP:rs373646964)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072850"
FT VARIANT 523
FT /note="V -> M (in FHCL1; Kuwait; dbSNP:rs28942080)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_005395"
FT VARIANT 526
FT /note="P -> S (in FHCL1; Cincinnati-3; unknown pathological
FT significance; dbSNP:rs730882106)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005396"
FT VARIANT 546
FT /note="G -> D (in Saint Omer; retention in the ER;
FT dbSNP:rs28942081)"
FT /evidence="ECO:0000269|PubMed:19520913"
FT /id="VAR_005397"
FT VARIANT 549
FT /note="G -> D (in FHCL1; Genoa; dbSNP:rs28941776)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005398"
FT VARIANT 564
FT /note="N -> H (in FHCL1; dbSNP:rs397509365)"
FT /evidence="ECO:0000269|PubMed:10090484,
FT ECO:0000269|PubMed:10532689, ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:7550239, ECO:0000269|PubMed:9143924"
FT /id="VAR_005399"
FT VARIANT 564
FT /note="N -> S (in FHCL1; Sicily; dbSNP:rs758194385)"
FT /evidence="ECO:0000269|PubMed:9654205"
FT /id="VAR_005400"
FT VARIANT 565
FT /note="G -> V (in Naples-2; dbSNP:rs28942082)"
FT /id="VAR_005401"
FT VARIANT 568
FT /note="L -> V (in FHCL1; Japanese patient;
FT dbSNP:rs746959386)"
FT /evidence="ECO:0000269|PubMed:10447263"
FT /id="VAR_008996"
FT VARIANT 574
FT /note="R -> C (in FHCL1; dbSNP:rs185098634)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072851"
FT VARIANT 574
FT /note="R -> H (in FHCL1; unknown pathological significance;
FT dbSNP:rs777188764)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072852"
FT VARIANT 577
FT /note="W -> G (in FHCL1; results in loss of receptor
FT expression at the cell surface; dbSNP:rs879255000)"
FT /evidence="ECO:0000269|PubMed:17347910,
FT ECO:0000269|PubMed:25378237"
FT /id="VAR_072853"
FT VARIANT 577
FT /note="W -> S (in FHCL1; unknown pathological significance;
FT dbSNP:rs138947766)"
FT /evidence="ECO:0000269|PubMed:10532689"
FT /id="VAR_072854"
FT VARIANT 579
FT /note="D -> N (in FHCL1; Cincinnati-4; less than 2%
FT receptor activity; dbSNP:rs875989929)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:7635461"
FT /id="VAR_005402"
FT VARIANT 579
FT /note="D -> Y (in FHCL1; dbSNP:rs875989929)"
FT /evidence="ECO:0000269|PubMed:10978268"
FT /id="VAR_062382"
FT VARIANT 585
FT /note="I -> T (in FHCL1; unknown pathological significance;
FT dbSNP:rs879255012)"
FT /evidence="ECO:0000269|PubMed:17347910"
FT /id="VAR_072855"
FT VARIANT 592
FT /note="G -> E (in FHCL1; Sicily; dbSNP:rs137929307)"
FT /evidence="ECO:0000269|PubMed:9654205"
FT /id="VAR_005403"
FT VARIANT 595
FT /note="R -> W (in FHCL1; unknown pathological significance;
FT dbSNP:rs373371572)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072856"
FT VARIANT 599
FT /note="L -> S (in London-5; dbSNP:rs879255025)"
FT /id="VAR_005404"
FT VARIANT 601
FT /note="D -> H (in FHCL1; unknown pathological significance;
FT dbSNP:rs753707206)"
FT /evidence="ECO:0000269|PubMed:24529145"
FT /id="VAR_072857"
FT VARIANT 608
FT /note="P -> S (in FHCL1; dbSNP:rs879255034)"
FT /evidence="ECO:0000269|PubMed:9852677"
FT /id="VAR_007989"
FT VARIANT 633
FT /note="R -> C (in FHCL1; dbSNP:rs746118995)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005405"
FT VARIANT 639
FT /note="V -> D (in FHCL1; dbSNP:rs794728584)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072858"
FT VARIANT 649
FT /note="P -> L (in FHCL1; dbSNP:rs879255081)"
FT /evidence="ECO:0000269|PubMed:9259195"
FT /id="VAR_005406"
FT VARIANT 667
FT /note="C -> Y (in FHCL1; French Canadian-2; 5% of French
FT Canadians; dbSNP:rs28942083)"
FT /evidence="ECO:0000269|PubMed:10206683,
FT ECO:0000269|PubMed:2318961"
FT /id="VAR_005407"
FT VARIANT 677
FT /note="C -> R (in FHCL1; New York-3; dbSNP:rs775092314)"
FT /evidence="ECO:0000269|PubMed:17142622"
FT /id="VAR_005408"
FT VARIANT 682
FT /note="L -> P (in Issoire; dbSNP:rs879255119)"
FT /id="VAR_005409"
FT VARIANT 685
FT /note="P -> L (in FHCL1; Gujerat/Zambia/Belgian/Dutch/
FT Sweden/Japan; dbSNP:rs28942084)"
FT /evidence="ECO:0000269|PubMed:1464748,
FT ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910,
FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:2726768,
FT ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:9254862"
FT /id="VAR_005410"
FT VARIANT 699
FT /note="P -> L (in FHCL1; unknown pathological significance;
FT dbSNP:rs201573863)"
FT /evidence="ECO:0000269|PubMed:10882754,
FT ECO:0000269|PubMed:24529145"
FT /id="VAR_013955"
FT VARIANT 700
FT /note="D -> E (in FHCL1; Spanish patient;
FT dbSNP:rs759858813)"
FT /evidence="ECO:0000269|PubMed:10206683"
FT /id="VAR_005412"
FT VARIANT 714
FT /note="E -> K (in FHCL1; Japanese patient;
FT dbSNP:rs869320652)"
FT /evidence="ECO:0000269|PubMed:10447263"
FT /id="VAR_008997"
FT VARIANT 726
FT /note="T -> I (in FHCL1; Paris-9; unknown pathological
FT significance; dbSNP:rs45508991)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:9259195"
FT /id="VAR_005413"
FT VARIANT 742
FT /note="T -> I (in dbSNP:rs767546791)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072859"
FT VARIANT 792
FT /note="I -> F (in Russia-2; dbSNP:rs761123215)"
FT /id="VAR_005414"
FT VARIANT 797
FT /note="V -> M (in FHCL1; La Havana patient;
FT dbSNP:rs750518671)"
FT /evidence="ECO:0000269|PubMed:24529145,
FT ECO:0000269|PubMed:7649549"
FT /id="VAR_005415"
FT VARIANT 799..801
FT /note="Missing (in FHCL1; Danish patient;
FT dbSNP:rs879255195)"
FT /evidence="ECO:0000269|PubMed:9143924"
FT /id="VAR_005416"
FT VARIANT 806
FT /note="V -> D (in FHCL1; unknown pathological significance;
FT dbSNP:rs879255208)"
FT /evidence="ECO:0000269|PubMed:11462246"
FT /id="VAR_072860"
FT VARIANT 814
FT /note="R -> Q (in FHCL1; unknown pathological significance;
FT dbSNP:rs5928)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10882754, ECO:0000269|PubMed:24529145"
FT /id="VAR_011864"
FT VARIANT 820..822
FT /note="Missing (in FHCL1)"
FT /id="VAR_005417"
FT VARIANT 825
FT /note="N -> K (in FHCL1; does not affect receptor
FT expression at the cell surface; does not affect LDL
FT binding; results in impaired LDL uptake and
FT internalization; dbSNP:rs374045590)"
FT /evidence="ECO:0000269|PubMed:10532689,
FT ECO:0000269|PubMed:25378237"
FT /id="VAR_072861"
FT VARIANT 826
FT /note="P -> S (in FHCL1; dbSNP:rs879255217)"
FT /evidence="ECO:0000269|PubMed:19319977"
FT /id="VAR_062383"
FT VARIANT 827
FT /note="V -> I (in New York-5; dbSNP:rs137853964)"
FT /id="VAR_005418"
FT VARIANT 828
FT /note="Y -> C (in FHCL1; J.D.Bari/Syria; 2-fold decreased
FT affinity for LDLRAP1; dbSNP:rs28942085)"
FT /evidence="ECO:0000269|PubMed:22509010,
FT ECO:0000269|PubMed:3955657"
FT /id="VAR_005419"
FT VARIANT 844
FT /note="G -> D (in Turku; dbSNP:rs121908037)"
FT /evidence="ECO:0000269|PubMed:7573037"
FT /id="VAR_005420"
FT MUTAGEN 811
FT /note="K->R: No change. No change; when associated with R-
FT 816 and R-830. Insensitive to MYLIP-triggered degradation;
FT when associated with R-816; R-830 and A-839."
FT /evidence="ECO:0000269|PubMed:19520913"
FT MUTAGEN 816
FT /note="K->R: No change. No change; when associated with R-
FT 830. No change; when associated with R-811 and R-830.
FT Insensitive to MYLIP-triggered degradation; when associated
FT with R-830 and A-839. Insensitive to MYLIP-triggered
FT degradation; when associated with R-811; R-830 and A-839."
FT /evidence="ECO:0000269|PubMed:19520913"
FT MUTAGEN 821
FT /note="I->A: 3-fold decreased affinity for LDLRAP1."
FT /evidence="ECO:0000269|PubMed:22509010"
FT MUTAGEN 821
FT /note="I->R: 10-fold decreased affinity for LDLRAP1."
FT /evidence="ECO:0000269|PubMed:22509010"
FT MUTAGEN 828
FT /note="Y->A: Abolishes interaction with ARRB2."
FT /evidence="ECO:0000269|PubMed:12944399"
FT MUTAGEN 829
FT /note="Q->A: Decreased affinity for LDLRAP1."
FT /evidence="ECO:0000269|PubMed:22509010"
FT MUTAGEN 830
FT /note="K->R: No change. No change; when associated with R-
FT 816. No change; when associated with R-811 and R-816.
FT Insensitive to MYLIP-triggered degradation; when associated
FT with A-839. Insensitive to MYLIP-triggered degradation;
FT when associated with R-816 and A-839. Insensitive to MYLIP-
FT triggered degradation; when associated with R-811; R-816
FT and A-839."
FT /evidence="ECO:0000269|PubMed:19520913"
FT MUTAGEN 839
FT /note="C->A: No change. Insensitive to MYLIP-triggered
FT degradation; when associated with R-830. Insensitive to
FT MYLIP-triggered degradation; when associated with R-816 and
FT R-830. Insensitive to MYLIP-triggered degradation; when
FT associated with R-811; R-816 and R-830."
FT /evidence="ECO:0000269|PubMed:19520913"
FT MUTAGEN 854
FT /note="S->A: No effect on receptor internalization."
FT /evidence="ECO:0000269|PubMed:12944399"
FT MUTAGEN 854
FT /note="S->D: Enhances interaction with ARRB2 and receptor
FT internalization."
FT /evidence="ECO:0000269|PubMed:12944399"
FT CONFLICT 31
FT /note="E -> D (in Ref. 4; BAG58495)"
FT /evidence="ECO:0000305"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:1F5Y"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1F5Y"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1LDL"
FT TURN 42..46
FT /evidence="ECO:0007829|PDB:1F5Y"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1F5Y"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:1F5Y"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:1F5Y"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:1LDL"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:5OYL"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:1LDR"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:5OYL"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:5OYL"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:5OYL"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1F5Y"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:5OYL"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:5OYL"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2FCW"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:2FCW"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:2FCW"
FT TURN 138..142
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 143..147
FT /evidence="ECO:0007829|PDB:2FCW"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:2LGP"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:2FCW"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:2LGP"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:2FCW"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:2FCW"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:2LGP"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:2FCW"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:2FCW"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:2LGP"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2LGP"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:2LGP"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:2LGP"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1AJJ"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:1AJJ"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:2LGP"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:1AJJ"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:1D2J"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:1D2J"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1D2J"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:1D2J"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1D2J"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:1D2J"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:1F8Z"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1F8Z"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:1XFE"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:1XFE"
FT TURN 293..296
FT /evidence="ECO:0007829|PDB:1XFE"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:1XFE"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:1XFE"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:2W2N"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:2W2N"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:2W2N"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:2W2N"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2W2N"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:1HZ8"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:2W2N"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:2W2N"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:2W2N"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:1HJ7"
FT STRAND 363..369
FT /evidence="ECO:0007829|PDB:1HJ7"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:3P5B"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:1HJ7"
FT STRAND 381..385
FT /evidence="ECO:0007829|PDB:1HZ8"
FT TURN 387..389
FT /evidence="ECO:0007829|PDB:3P5B"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:1HZ8"
FT STRAND 400..404
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 406..413
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 427..435
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 436..439
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 446..449
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 466..469
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 478..482
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 483..486
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 487..492
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 497..502
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 505..513
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 519..525
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 526..529
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 530..535
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 541..546
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 552..556
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 563..569
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 570..573
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 574..579
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 580..583
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 584..589
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 596..600
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 602..605
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 606..614
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 617..622
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 623..626
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 627..632
FT /evidence="ECO:0007829|PDB:1IJQ"
FT TURN 633..635
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 640..643
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 652..656
FT /evidence="ECO:0007829|PDB:1IJQ"
FT HELIX 657..659
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 668..672
FT /evidence="ECO:0007829|PDB:1IJQ"
FT HELIX 673..676
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 678..683
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 693..697
FT /evidence="ECO:0007829|PDB:1IJQ"
FT STRAND 708..713
FT /evidence="ECO:0007829|PDB:3P5B"
FT STRAND 821..824
FT /evidence="ECO:0007829|PDB:3SO6"
FT TURN 826..829
FT /evidence="ECO:0007829|PDB:3SO6"
SQ SEQUENCE 860 AA; 95376 MW; A4C28E9B8BADAD5E CRC64;
MGPWGWKLRW TVALLLAAAG TAVGDRCERN EFQCQDGKCI SYKWVCDGSA ECQDGSDESQ
ETCLSVTCKS GDFSCGGRVN RCIPQFWRCD GQVDCDNGSD EQGCPPKTCS QDEFRCHDGK
CISRQFVCDS DRDCLDGSDE ASCPVLTCGP ASFQCNSSTC IPQLWACDND PDCEDGSDEW
PQRCRGLYVF QGDSSPCSAF EFHCLSGECI HSSWRCDGGP DCKDKSDEEN CAVATCRPDE
FQCSDGNCIH GSRQCDREYD CKDMSDEVGC VNVTLCEGPN KFKCHSGECI TLDKVCNMAR
DCRDWSDEPI KECGTNECLD NNGGCSHVCN DLKIGYECLC PDGFQLVAQR RCEDIDECQD
PDTCSQLCVN LEGGYKCQCE EGFQLDPHTK ACKAVGSIAY LFFTNRHEVR KMTLDRSEYT
SLIPNLRNVV ALDTEVASNR IYWSDLSQRM ICSTQLDRAH GVSSYDTVIS RDIQAPDGLA
VDWIHSNIYW TDSVLGTVSV ADTKGVKRKT LFRENGSKPR AIVVDPVHGF MYWTDWGTPA
KIKKGGLNGV DIYSLVTENI QWPNGITLDL LSGRLYWVDS KLHSISSIDV NGGNRKTILE
DEKRLAHPFS LAVFEDKVFW TDIINEAIFS ANRLTGSDVN LLAENLLSPE DMVLFHNLTQ
PRGVNWCERT TLSNGGCQYL CLPAPQINPH SPKFTCACPD GMLLARDMRS CLTEAEAAVA
TQETSTVRLK VSSTAVRTQH TTTRPVPDTS RLPGATPGLT TVEIVTMSHQ ALGDVAGRGN
EKKPSSVRAL SIVLPIVLLV FLCLGVFLLW KNWRLKNINS INFDNPVYQK TTEDEVHICH
NQDGYSYPSR QMVSLEDDVA
