MKS3_HUMAN
ID MKS3_HUMAN Reviewed; 995 AA.
AC Q5HYA8; B3KRU5; B3KT47; G5E9H2; Q3ZCX3; Q7Z5T8; Q8IZ06;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Meckelin;
DE AltName: Full=Meckel syndrome type 3 protein;
DE AltName: Full=Transmembrane protein 67;
DE Flags: Precursor;
GN Name=TMEM67; Synonyms=MKS3;
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 [LARGE SCALE MRNA], AND VARIANT VAL-604.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-995, AND VARIANT VAL-604.
RC TISSUE=Corpus callosum;
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] OF 5-995.
RC TISSUE=Testis;
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 [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT MKS3
RP PRO-376, FUNCTION, AND INTERACTION WITH MKS1.
RX PubMed=17185389; DOI=10.1093/hmg/ddl459;
RA Dawe H.R., Smith U.M., Cullinane A.R., Gerrelli D., Cox P., Badano J.L.,
RA Blair-Reid S., Sriram N., Katsanis N., Attie-Bitach T., Afford S.C.,
RA Copp A.J., Kelly D.A., Gull K., Johnson C.A.;
RT "The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are
RT required for primary cilium formation.";
RL Hum. Mol. Genet. 16:173-186(2007).
RN [7]
RP FUNCTION.
RX PubMed=19515853; DOI=10.1093/hmg/ddp272;
RA Tammachote R., Hommerding C.J., Sinders R.M., Miller C.A., Czarnecki P.G.,
RA Leightner A.C., Salisbury J.L., Ward C.J., Torres V.E., Gattone V.H. II,
RA Harris P.C.;
RT "Ciliary and centrosomal defects associated with mutation and depletion of
RT the Meckel syndrome genes MKS1 and MKS3.";
RL Hum. Mol. Genet. 18:3311-3323(2009).
RN [8]
RP SUBCELLULAR LOCATION, TOPOLOGY, FUNCTION, AND INTERACTION WITH DNAJB9;
RP DNAJC10 AND SFTPC.
RX PubMed=19815549; DOI=10.1074/jbc.m109.034371;
RA Wang M., Bridges J.P., Na C.L., Xu Y., Weaver T.E.;
RT "Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-
RT associated degradation of surfactant protein C.";
RL J. Biol. Chem. 284:33377-33383(2009).
RN [9]
RP SUBCELLULAR LOCATION, INTERACTION WITH SYNE2, AND FUNCTION.
RX PubMed=19596800; DOI=10.1242/jcs.043794;
RA Dawe H.R., Adams M., Wheway G., Szymanska K., Logan C.V., Noegel A.A.,
RA Gull K., Johnson C.A.;
RT "Nesprin-2 interacts with meckelin and mediates ciliogenesis via
RT remodelling of the actin cytoskeleton.";
RL J. Cell Sci. 122:2716-2726(2009).
RN [10]
RP INTERACTION WITH FLNA, AND SUBCELLULAR LOCATION.
RX PubMed=22121117; DOI=10.1093/hmg/ddr557;
RA Adams M., Simms R.J., Abdelhamed Z., Dawe H.R., Szymanska K., Logan C.V.,
RA Wheway G., Pitt E., Gull K., Knowles M.A., Blair E., Cross S.H.,
RA Sayer J.A., Johnson C.A.;
RT "A meckelin-filamin A interaction mediates ciliogenesis.";
RL Hum. Mol. Genet. 21:1272-1286(2012).
RN [11]
RP INTERACTION WITH TMEM218.
RX PubMed=35137054; DOI=10.1093/hmg/ddac027;
RA Epting D., Decker E., Ott E., Eisenberger T., Bader I., Bachmann N.,
RA Bergmann C.;
RT "The ciliary transition zone protein TMEM218 synergistically interacts with
RT the NPHP module and its reduced dosage leads to a wide range of syndromic
RT ciliopathies.";
RL Hum. Mol. Genet. 0:0-0(2022).
RN [12]
RP VARIANT MKS3 PRO-376, AND TISSUE SPECIFICITY.
RX PubMed=16415887; DOI=10.1038/ng1713;
RA Smith U.M., Consugar M., Tee L.J., McKee B.M., Maina E.N., Whelan S.,
RA Morgan N.V., Goranson E., Gissen P., Lilliquist S., Aligianis I.A.,
RA Ward C.J., Pasha S., Punyashthiti R., Malik Sharif S., Batman P.A.,
RA Bennett C.P., Woods C.G., McKeown C., Bucourt M., Miller C.A., Cox P.,
RA Algazali L., Trembath R.C., Torres V.E., Attie-Bitach T., Kelly D.A.,
RA Maher E.R., Gattone V.H., Harris P.C., Johnson C.A.;
RT "The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber
RT syndrome and the wpk rat.";
RL Nat. Genet. 38:191-196(2006).
RN [13]
RP VARIANTS JBTS6 CYS-513 AND GLU-545.
RX PubMed=17160906; DOI=10.1086/510499;
RA Baala L., Romano S., Khaddour R., Saunier S., Smith U.M., Audollent S.,
RA Ozilou C., Faivre L., Laurent N., Foliguet B., Munnich A., Lyonnet S.,
RA Salomon R., Encha-Razavi F., Gubler M.-C., Boddaert N., de Lonlay P.,
RA Johnson C.A., Vekemans M., Antignac C., Attie-Bitach T.;
RT "The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome.";
RL Am. J. Hum. Genet. 80:186-194(2007).
RN [14]
RP VARIANTS MKS3 208-ARG--ILE-995 DEL; THR-252; GLN-440; 451-ARG--ILE-995 DEL
RP AND PRO-966.
RX PubMed=17377820; DOI=10.1007/s00439-007-0341-3;
RA Consugar M.B., Kubly V.J., Lager D.J., Hommerding C.J., Wong W.C.,
RA Bakker E., Gattone V.H. II, Torres V.E., Breuning M.H., Harris P.C.;
RT "Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic
RT differences between MKS1 and MKS3.";
RL Hum. Genet. 121:591-599(2007).
RN [15]
RP VARIANTS ALA-218; ASN-261; CYS-320 AND VAL-437, AND INVOLVEMENT IN BBS14.
RX PubMed=18327255; DOI=10.1038/ng.97;
RA Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S.,
RA Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L.,
RA Badano J.L., Katsanis N.;
RT "Hypomorphic mutations in syndromic encephalocele genes are associated with
RT Bardet-Biedl syndrome.";
RL Nat. Genet. 40:443-448(2008).
RN [16]
RP ERRATUM OF PUBMED:18327255.
RA Leitch C.C., Zaghloul N.A., Davis E.E., Stoetzel C., Diaz-Font A., Rix S.,
RA Alfadhel M., Lewis R.A., Eyaid W., Banin E., Dollfus H., Beales P.L.,
RA Badano J.L., Katsanis N.;
RL Nat. Genet. 40:927-927(2008).
RN [17]
RP VARIANTS COACH1 ARG-130; LYS-372; GLN-440; SER-590; GLY-728; ARG-782;
RP SER-820 AND THR-833.
RX PubMed=19058225; DOI=10.1002/humu.20924;
RA Brancati F., Iannicelli M., Travaglini L., Mazzotta A., Bertini E.,
RA Boltshauser E., D'Arrigo S., Emma F., Fazzi E., Gallizzi R., Gentile M.,
RA Loncarevic D., Mejaski-Bosnjak V., Pantaleoni C., Rigoli L.,
RA Salpietro C.D., Signorini S., Stringini G.R., Verloes A., Zabloka D.,
RA Dallapiccola B., Gleeson J.G., Valente E.M.;
RT "MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert
RT Syndrome related disorder with liver involvement.";
RL Hum. Mutat. 30:E432-E442(2009).
RN [18]
RP VARIANTS MKS3 CYS-54; PHE-245; THR-252; CYS-296 GLN-440; CYS-513; ARG-615
RP AND PRO-966.
RX PubMed=19466712; DOI=10.1002/humu.21057;
RA Tallila J., Salonen R., Kohlschmidt N., Peltonen L., Kestilae M.;
RT "Mutation spectrum of Meckel syndrome genes: one group of syndromes or
RT several distinct groups?";
RL Hum. Mutat. 30:E813-E830(2009).
RN [19]
RP VARIANTS NPHP11 LEU-290; ARG-615; SER-821 AND ARG-821, AND VARIANTS JBTS6
RP 44-GLN--ILE-995 DEL; 208-ARG--ILE-995 DEL; THR-252; ARG-615; ARG-821 AND
RP THR-833.
RX PubMed=19508969; DOI=10.1136/jmg.2009.066613;
RA Otto E.A., Tory K., Attanasio M., Zhou W., Chaki M., Paruchuri Y.,
RA Wise E.L., Wolf M.T.F., Utsch B., Becker C., Nuernberg G., Nuernberg P.,
RA Nayir A., Saunier S., Antignac C., Hildebrandt F.;
RT "Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis
RT with liver fibrosis (NPHP11).";
RL J. Med. Genet. 46:663-670(2009).
RN [20]
RP VARIANTS LYS-90; LYS-124; GLU-301; ASP-569; VAL-616 AND ARG-739, AND
RP VARIANTS MKS3 SER-349; LEU-441; ARG-668; GLU-786 AND CYS-843.
RX PubMed=20232449; DOI=10.1002/humu.21239;
RG International JSRD Study Group;
RA Iannicelli M., Brancati F., Mougou-Zerelli S., Mazzotta A., Thomas S.,
RA Elkhartoufi N., Travaglini L., Gomes C., Ardissino G.L., Bertini E.,
RA Boltshauser E., Castorina P., D'Arrigo S., Fischetto R., Leroy B.,
RA Loget P., Bonniere M., Starck L., Tantau J., Gentilin B., Majore S.,
RA Swistun D., Flori E., Lalatta F., Pantaleoni C., Penzien J., Grammatico P.,
RA Dallapiccola B., Gleeson J.G., Attie-Bitach T., Valente E.M.;
RT "Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-
RT related ciliopathies.";
RL Hum. Mutat. 31:E1319-E1331(2010).
RN [21]
RP VARIANTS COACH1 ASN-99; ARG-130; GLN-172; THR-242; THR-252; VAL-257;
RP SER-349; LEU-358; LYS-372; GLU-376; CYS-441; SER-485; CYS-513; ARG-615;
RP LEU-637; THR-833; PRO-841 AND CYS-942, AND VARIANTS JBTS6 ARG-82 AND
RP SER-82.
RX PubMed=19574260; DOI=10.1136/jmg.2009.067249;
RA Doherty D., Parisi M.A., Finn L.S., Gunay-Aygun M., Al-Mateen M., Bates D.,
RA Clericuzio C., Demir H., Dorschner M., van Essen A.J., Gahl W.A.,
RA Gentile M., Gorden N.T., Hikida A., Knutzen D., Ozyurek H., Phelps I.,
RA Rosenthal P., Verloes A., Weigand H., Chance P.F., Dobyns W.B., Glass I.A.;
RT "Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome
RT (Joubert syndrome with congenital hepatic fibrosis).";
RL J. Med. Genet. 47:8-21(2010).
RN [22]
RP VARIANTS JBTS6 LEU-358 AND THR-833.
RX PubMed=21633164; DOI=10.1172/jci43639;
RA Dafinger C., Liebau M.C., Elsayed S.M., Hellenbroich Y., Boltshauser E.,
RA Korenke G.C., Fabretti F., Janecke A.R., Ebermann I., Nurnberg G.,
RA Nurnberg P., Zentgraf H., Koerber F., Addicks K., Elsobky E., Benzing T.,
RA Schermer B., Bolz H.J.;
RT "Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and
RT microtubule dynamics.";
RL J. Clin. Invest. 121:2662-2667(2011).
RN [23]
RP VARIANT JBTS6 ALA-711.
RX PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009;
RG Care4Rare Canada Consortium;
RA Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H.,
RA Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A.,
RA Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B.,
RA Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C.,
RA Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M.,
RA Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K.,
RA Shalev S., Michaud J.L.;
RT "Joubert Syndrome in French Canadians and Identification of Mutations in
RT CEP104.";
RL Am. J. Hum. Genet. 97:744-753(2015).
RN [24]
RP INVOLVEMENT IN COACH1, VARIANT COACH1 ALA-132, AND CHARACTERIZATION OF
RP VARIANT COACH1 ALA-132.
RX PubMed=28860541; DOI=10.1038/s41598-017-10652-z;
RA Lee S.H., Nam T.S., Li W., Kim J.H., Yoon W., Choi Y.D., Kim K.H., Cai H.,
RA Kim M.J., Kim C., Choy H.E., Kim N., Chay K.O., Kim M.K., Choi S.Y.;
RT "Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.";
RL Sci. Rep. 7:10222-10222(2017).
RN [25]
RP VARIANTS RHYNS 208-ARG--ILE-995 DEL AND GLY-430, AND INVOLVEMENT IN RHYNS.
RX PubMed=29891882; DOI=10.1038/s41431-018-0183-6;
RG Undiagnosed Disease Network Italy;
RA Brancati F., Camerota L., Colao E., Vega-Warner V., Zhao X., Zhang R.,
RA Bottillo I., Castori M., Caglioti A., Sangiuolo F., Novelli G.,
RA Perrotti N., Otto E.A.;
RT "Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome.";
RL Eur. J. Hum. Genet. 26:1266-1271(2018).
CC -!- FUNCTION: Required for ciliary structure and function. Part of the
CC tectonic-like complex which is required for tissue-specific
CC ciliogenesis and may regulate ciliary membrane composition (By
CC similarity). Involved in centrosome migration to the apical cell
CC surface during early ciliogenesis. Involved in the regulation of cilia
CC length and appropriate number through the control of centrosome
CC duplication. Required for cell branching morphology. Essential for
CC endoplasmic reticulum-associated degradation (ERAD) of surfactant
CC protein C (SFTPC). {ECO:0000250, ECO:0000269|PubMed:17185389,
CC ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:19596800,
CC ECO:0000269|PubMed:19815549}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex) (By
CC similarity). Interacts with DNAJB9, DNAJC10 and mutated SFTPC.
CC Interacts with SYNE2 during the early establishment of cell polarity.
CC Interacts (via C-terminus) with FLNA. Interacts with TMEM218
CC (PubMed:35137054). {ECO:0000250|UniProtKB:Q8BR76,
CC ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19596800,
CC ECO:0000269|PubMed:19815549, ECO:0000269|PubMed:22121117,
CC ECO:0000269|PubMed:35137054}.
CC -!- INTERACTION:
CC Q5HYA8; P05067-2: APP; NbExp=3; IntAct=EBI-11334880, EBI-17264467;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17185389};
CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:19815549}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, cilium {ECO:0000269|PubMed:17185389}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:22121117}. Note=Localizes at the transition zone, a
CC region between the basal body and the ciliary axoneme
CC (PubMed:22121117). {ECO:0000269|PubMed:22121117}.
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues.
CC Expressed at higher level in spinal cord. {ECO:0000269|PubMed:16415887,
CC ECO:0000269|PubMed:17185389}.
CC -!- DISEASE: Note=TMEM67 mutations result in ciliary dysfunction leading to
CC a broad spectrum of disorders, collectively termed ciliopathies.
CC Overlapping clinical features include retinal degeneration, renal
CC cystic disease, skeletal abnormalities, fibrosis of various organ, and
CC a complex range of anatomical and functional defects of the central and
CC peripheral nervous system. The ciliopathy range of diseases includes
CC Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and
CC nephronophtisis among others. Single-locus allelism is insufficient to
CC explain the variable penetrance and expressivity of such disorders,
CC leading to the suggestion that variations across multiple sites of the
CC ciliary proteome influence the clinical outcome.
CC {ECO:0000269|PubMed:18327255, ECO:0000269|PubMed:21633164}.
CC -!- DISEASE: Meckel syndrome 3 (MKS3) [MIM:607361]: A disorder
CC characterized by a combination of renal cysts and variably associated
CC features including developmental anomalies of the central nervous
CC system (typically encephalocele), hepatic ductal dysplasia and cysts,
CC and polydactyly. {ECO:0000269|PubMed:16415887,
CC ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:17377820,
CC ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:20232449}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Joubert syndrome 6 (JBTS6) [MIM:610688]: A disorder presenting
CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal
CC breathing abnormalities and psychomotor delay. Neuroradiologically, it
CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened
CC and reoriented superior cerebellar peduncles, and an abnormally large
CC interpeduncular fossa, giving the appearance of a molar tooth on
CC transaxial slices (molar tooth sign). Additional variable features
CC include retinal dystrophy and renal disease.
CC {ECO:0000269|PubMed:17160906, ECO:0000269|PubMed:19508969,
CC ECO:0000269|PubMed:19574260, ECO:0000269|PubMed:21633164,
CC ECO:0000269|PubMed:26477546}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Bardet-Biedl syndrome 14 (BBS14) [MIM:615991]: A syndrome
CC characterized by usually severe pigmentary retinopathy, early-onset
CC obesity, polydactyly, hypogenitalism, renal malformation and
CC intellectual disability. Secondary features include diabetes mellitus,
CC hypertension and congenital heart disease. Bardet-Biedl syndrome
CC inheritance is autosomal recessive, but three mutated alleles (two at
CC one locus, and a third at a second locus) may be required for clinical
CC manifestation of some forms of the disease.
CC {ECO:0000269|PubMed:18327255}. Note=The gene represented in this entry
CC may act as a disease modifier. TMEM67 variations may influence the
CC expression of Bardet-Biedl syndrome in patients who have causative
CC mutations in other genes. Heterozygosity for a complex mutation in the
CC TMEM67 gene coding for a protein with 2 in cis changes, and
CC homozygosity for a truncating mutation of the CEP290 gene has been
CC found in a patient with Bardet-Biedl syndrome 14.
CC -!- DISEASE: COACH syndrome 1 (COACH1) [MIM:216360]: A form of COACH
CC syndrome, a disorder characterized by cerebellar vermis hypoplasia,
CC developmental delay, impaired intellectual development, ataxia, and
CC hepatic fibrosis. Patients present the molar tooth sign, a midbrain-
CC hindbrain malformation pathognomonic for Joubert syndrome and related
CC disorders. Other features, such as coloboma and renal cysts, may be
CC variable. COACH1 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:19058225, ECO:0000269|PubMed:19574260,
CC ECO:0000269|PubMed:28860541}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Nephronophthisis 11 (NPHP11) [MIM:613550]: A disorder
CC characterized by the association of nephronophthisis with hepatic
CC fibrosis. Nephronophthisis is a progressive tubulo-interstitial kidney
CC disorder histologically characterized by modifications of the tubules
CC with thickening of the basement membrane, interstitial fibrosis and, in
CC the advanced stages, medullary cysts. Typical clinical features are
CC chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and
CC growth retardation. Associations with extrarenal symptoms, especially
CC ocular lesions, are frequent. {ECO:0000269|PubMed:19508969}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: RHYNS syndrome (RHYNS) [MIM:602152]: An autosomal recessive
CC syndrome characterized by gaze palsy, retinitis pigmentosa,
CC sensorineural hearing loss, hypopituitarism, nephronophthisis, and
CC skeletal dysplasia. {ECO:0000269|PubMed:29891882}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32835.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG52507.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAG52959.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW91703.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX648768; CAI45999.1; -; mRNA.
DR EMBL; AC010834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471060; EAW91703.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK092244; BAG52507.1; ALT_SEQ; mRNA.
DR EMBL; AK094935; BAG52959.1; ALT_INIT; mRNA.
DR EMBL; BC032835; AAH32835.1; ALT_INIT; mRNA.
DR CCDS; CCDS6258.2; -.
DR PDB; 7FH1; EM; 3.34 A; A/B=1-995.
DR PDBsum; 7FH1; -.
DR AlphaFoldDB; Q5HYA8; -.
DR SMR; Q5HYA8; -.
DR BioGRID; 124799; 145.
DR CORUM; Q5HYA8; -.
DR IntAct; Q5HYA8; 72.
DR STRING; 9606.ENSP00000389998; -.
DR TCDB; 9.B.77.1.1; the meckel syndrome protein (meckelin) family.
DR GlyGen; Q5HYA8; 2 sites.
DR iPTMnet; Q5HYA8; -.
DR PhosphoSitePlus; Q5HYA8; -.
DR BioMuta; TMEM67; -.
DR DMDM; 317373389; -.
DR EPD; Q5HYA8; -.
DR jPOST; Q5HYA8; -.
DR MassIVE; Q5HYA8; -.
DR MaxQB; Q5HYA8; -.
DR PaxDb; Q5HYA8; -.
DR PeptideAtlas; Q5HYA8; -.
DR PRIDE; Q5HYA8; -.
DR ProteomicsDB; 33938; -.
DR Antibodypedia; 25725; 91 antibodies from 24 providers.
DR DNASU; 91147; -.
DR Ensembl; ENST00000323130.8; ENSP00000314488.4; ENSG00000164953.17.
DR Ensembl; ENST00000453321.8; ENSP00000389998.3; ENSG00000164953.17.
DR GeneID; 91147; -.
DR MANE-Select; ENST00000453321.8; ENSP00000389998.3; NM_153704.6; NP_714915.3.
DR UCSC; uc003yga.5; human.
DR CTD; 91147; -.
DR DisGeNET; 91147; -.
DR GeneCards; TMEM67; -.
DR GeneReviews; TMEM67; -.
DR HGNC; HGNC:28396; TMEM67.
DR HPA; ENSG00000164953; Low tissue specificity.
DR MalaCards; TMEM67; -.
DR MIM; 216360; phenotype.
DR MIM; 602152; phenotype.
DR MIM; 607361; phenotype.
DR MIM; 609884; gene.
DR MIM; 610688; phenotype.
DR MIM; 613550; phenotype.
DR MIM; 615991; phenotype.
DR neXtProt; NX_Q5HYA8; -.
DR OpenTargets; ENSG00000164953; -.
DR Orphanet; 475; Joubert syndrome.
DR Orphanet; 1454; Joubert syndrome with hepatic defect.
DR Orphanet; 564; Meckel syndrome.
DR Orphanet; 140976; RHYNS syndrome.
DR Orphanet; 84081; Senior-Boichis syndrome.
DR PharmGKB; PA142670780; -.
DR VEuPathDB; HostDB:ENSG00000164953; -.
DR eggNOG; KOG4611; Eukaryota.
DR GeneTree; ENSGT00390000010606; -.
DR InParanoid; Q5HYA8; -.
DR OMA; TNMEEMS; -.
DR OrthoDB; 1149465at2759; -.
DR PhylomeDB; Q5HYA8; -.
DR TreeFam; TF317053; -.
DR PathwayCommons; Q5HYA8; -.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SignaLink; Q5HYA8; -.
DR BioGRID-ORCS; 91147; 5 hits in 1068 CRISPR screens.
DR ChiTaRS; TMEM67; human.
DR GeneWiki; TMEM67; -.
DR GenomeRNAi; 91147; -.
DR Pharos; Q5HYA8; Tbio.
DR PRO; PR:Q5HYA8; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q5HYA8; protein.
DR Bgee; ENSG00000164953; Expressed in buccal mucosa cell and 136 other tissues.
DR ExpressionAtlas; Q5HYA8; baseline and differential.
DR Genevisible; Q5HYA8; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IDA:UniProtKB.
DR GO; GO:0035869; C:ciliary transition zone; IDA:WormBase.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB.
DR GO; GO:0031005; F:filamin binding; IPI:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IPI:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0010826; P:negative regulation of centrosome duplication; IMP:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR019170; Meckelin.
DR PANTHER; PTHR21274; PTHR21274; 1.
DR Pfam; PF09773; Meckelin; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Bardet-Biedl syndrome; Cell membrane; Cell projection;
KW Ciliopathy; Cilium; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Deafness; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW Intellectual disability; Joubert syndrome; Meckel syndrome; Membrane;
KW Nephronophthisis; Obesity; Reference proteome; Retinitis pigmentosa;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..995
FT /note="Meckelin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000225689"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 570..590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 609..629
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 689..709
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 734..754
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 939..959
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 44..995
FT /note="Missing (in JBTS6)"
FT /evidence="ECO:0000269|PubMed:19508969"
FT /id="VAR_081741"
FT VARIANT 54
FT /note="Y -> C (in MKS3; unknown pathological significance;
FT dbSNP:rs386834188)"
FT /evidence="ECO:0000269|PubMed:19466712"
FT /id="VAR_062310"
FT VARIANT 82
FT /note="P -> R (in JBTS6; unknown pathological significance;
FT dbSNP:rs772437766)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063783"
FT VARIANT 82
FT /note="P -> S (in JBTS6; unknown pathological significance;
FT dbSNP:rs762543032)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063784"
FT VARIANT 90
FT /note="N -> K (probable disease-associated variant found in
FT Joubert syndrome-related disorder)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076871"
FT VARIANT 99
FT /note="K -> N (in COACH1; unknown pathological
FT significance; dbSNP:rs797046045)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063785"
FT VARIANT 124
FT /note="E -> K (probable disease-associated variant found in
FT Joubert syndrome-related disorder; dbSNP:rs375824494)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076872"
FT VARIANT 130
FT /note="P -> R (in COACH1; dbSNP:rs863225226)"
FT /evidence="ECO:0000269|PubMed:19058225,
FT ECO:0000269|PubMed:19574260"
FT /id="VAR_063786"
FT VARIANT 132
FT /note="G -> A (in COACH1; does not affect protein
FT abundance; fails to rescue the hydrocephalus phenotype in a
FT zebrafish model; dbSNP:rs1490496033)"
FT /evidence="ECO:0000269|PubMed:28860541"
FT /id="VAR_079632"
FT VARIANT 172
FT /note="R -> Q (in COACH1; unknown pathological
FT significance; dbSNP:rs750950408)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063787"
FT VARIANT 208..995
FT /note="Missing (in JBTS6, MKS3 and RHYNS)"
FT /evidence="ECO:0000269|PubMed:17377820,
FT ECO:0000269|PubMed:19508969, ECO:0000269|PubMed:29891882"
FT /id="VAR_081742"
FT VARIANT 218
FT /note="G -> A (in dbSNP:rs202036490)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062311"
FT VARIANT 242
FT /note="N -> T (in COACH1)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063788"
FT VARIANT 245
FT /note="S -> F (in MKS3; unknown pathological significance;
FT dbSNP:rs386834206)"
FT /evidence="ECO:0000269|PubMed:19466712"
FT /id="VAR_062312"
FT VARIANT 252
FT /note="M -> T (in MKS3, JBTS6 and COACH1;
FT dbSNP:rs202149403)"
FT /evidence="ECO:0000269|PubMed:17377820,
FT ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:19508969,
FT ECO:0000269|PubMed:19574260"
FT /id="VAR_062313"
FT VARIANT 257
FT /note="M -> V (in COACH1; unknown pathological
FT significance; dbSNP:rs863225227)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063789"
FT VARIANT 261
FT /note="D -> N (in dbSNP:rs35793208)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062314"
FT VARIANT 290
FT /note="W -> L (in NPHP11; dbSNP:rs267607117)"
FT /evidence="ECO:0000269|PubMed:19508969"
FT /id="VAR_064185"
FT VARIANT 296
FT /note="W -> C (in MKS3; unknown pathological significance;
FT dbSNP:rs386834208)"
FT /id="VAR_062315"
FT VARIANT 301
FT /note="D -> E (probable disease-associated variant found in
FT Joubert syndrome-related disorder; dbSNP:rs756906837)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076873"
FT VARIANT 320
FT /note="S -> C (is a modifier of Bardet-Biedl syndrome;
FT found in a BBS14 patient also carrying a homozygous
FT truncating mutation of the CEP290 gene; dbSNP:rs111619594)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062316"
FT VARIANT 349
FT /note="L -> S (in COACH1 and MKS3; dbSNP:rs386834180)"
FT /evidence="ECO:0000269|PubMed:19574260,
FT ECO:0000269|PubMed:20232449"
FT /id="VAR_063790"
FT VARIANT 358
FT /note="P -> L (in COACH1 and JBTS6; found in a patient with
FT Joubert syndrome that also carries mutation 1329-R--S-1332
FT Del in KIF7; dbSNP:rs863225232)"
FT /evidence="ECO:0000269|PubMed:19574260,
FT ECO:0000269|PubMed:21633164"
FT /id="VAR_063791"
FT VARIANT 372
FT /note="T -> K (in COACH1; dbSNP:rs863225235)"
FT /evidence="ECO:0000269|PubMed:19058225,
FT ECO:0000269|PubMed:19574260"
FT /id="VAR_063792"
FT VARIANT 376
FT /note="Q -> E (in COACH1; unknown pathological
FT significance; dbSNP:rs863225231)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063793"
FT VARIANT 376
FT /note="Q -> P (in MKS3; leads to endoplasmic reticulum
FT retention and prevents localization at the cell membrane;
FT dbSNP:rs137853106)"
FT /evidence="ECO:0000269|PubMed:16415887,
FT ECO:0000269|PubMed:17185389"
FT /id="VAR_025474"
FT VARIANT 430
FT /note="D -> G (in RHYNS; may result in exon 13 skipping)"
FT /evidence="ECO:0000269|PubMed:29891882"
FT /id="VAR_081743"
FT VARIANT 437
FT /note="L -> V (in dbSNP:rs35765535)"
FT /evidence="ECO:0000269|PubMed:18327255"
FT /id="VAR_062317"
FT VARIANT 440
FT /note="R -> Q (in MKS3 and COACH1; dbSNP:rs386834182)"
FT /evidence="ECO:0000269|PubMed:17377820,
FT ECO:0000269|PubMed:19058225, ECO:0000269|PubMed:19466712"
FT /id="VAR_062318"
FT VARIANT 441
FT /note="R -> C (in COACH1; unknown pathological
FT significance; dbSNP:rs752362727)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063794"
FT VARIANT 441
FT /note="R -> L (in MKS3; dbSNP:rs386834183)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076874"
FT VARIANT 451..995
FT /note="Missing (in MKS3)"
FT /evidence="ECO:0000269|PubMed:17377820"
FT /id="VAR_081744"
FT VARIANT 485
FT /note="P -> S (in COACH1; unknown pathological
FT significance; dbSNP:rs863225228)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063795"
FT VARIANT 513
FT /note="Y -> C (in JBTS6, MKS3 and COACH1;
FT dbSNP:rs137853107)"
FT /evidence="ECO:0000269|PubMed:17160906,
FT ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:19574260"
FT /id="VAR_031987"
FT VARIANT 545
FT /note="G -> E (in JBTS6; dbSNP:rs267607114)"
FT /evidence="ECO:0000269|PubMed:17160906"
FT /id="VAR_031988"
FT VARIANT 569
FT /note="G -> D (probable disease-associated variant found in
FT Joubert syndrome-related disorder; dbSNP:rs1017800436)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076875"
FT VARIANT 590
FT /note="F -> S (in COACH1; dbSNP:rs267607115)"
FT /evidence="ECO:0000269|PubMed:19058225"
FT /id="VAR_063796"
FT VARIANT 604
FT /note="I -> V (in dbSNP:rs3134031)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_025475"
FT VARIANT 615
FT /note="C -> R (in MKS3, COACH1 and NPHP11;
FT dbSNP:rs201893408)"
FT /evidence="ECO:0000269|PubMed:19466712,
FT ECO:0000269|PubMed:19508969, ECO:0000269|PubMed:19574260"
FT /id="VAR_062319"
FT VARIANT 616
FT /note="A -> V (probable disease-associated variant found in
FT Joubert syndrome-related disorder; dbSNP:rs757204749)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076876"
FT VARIANT 637
FT /note="F -> L (in COACH1; unknown pathological
FT significance; dbSNP:rs863225225)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063797"
FT VARIANT 668
FT /note="W -> R (in MKS3; dbSNP:rs386834189)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076877"
FT VARIANT 711
FT /note="D -> A (in JBTS6; dbSNP:rs781383498)"
FT /evidence="ECO:0000269|PubMed:26477546"
FT /id="VAR_075699"
FT VARIANT 728
FT /note="S -> G (in COACH1)"
FT /evidence="ECO:0000269|PubMed:19058225"
FT /id="VAR_063798"
FT VARIANT 739
FT /note="L -> R (probable disease-associated variant found in
FT Joubert syndrome-related disorder)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076878"
FT VARIANT 782
FT /note="H -> R (in COACH1; dbSNP:rs777137476)"
FT /evidence="ECO:0000269|PubMed:19058225"
FT /id="VAR_063799"
FT VARIANT 786
FT /note="G -> E (in MKS3; dbSNP:rs386834193)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076879"
FT VARIANT 820
FT /note="R -> S (in COACH1)"
FT /evidence="ECO:0000269|PubMed:19058225"
FT /id="VAR_063800"
FT VARIANT 821
FT /note="G -> R (in NPHP11; dbSNP:rs267607116)"
FT /evidence="ECO:0000269|PubMed:19508969"
FT /id="VAR_064186"
FT VARIANT 821
FT /note="G -> S (in NPHP11; dbSNP:rs267607116)"
FT /evidence="ECO:0000269|PubMed:19508969"
FT /id="VAR_064187"
FT VARIANT 833
FT /note="I -> T (in COACH1 and JBTS6; found in a patient with
FT Joubert syndrome that also carries mutation 1329-R--S-1332
FT Del in KIF7; dbSNP:rs267607119)"
FT /evidence="ECO:0000269|PubMed:19058225,
FT ECO:0000269|PubMed:19508969, ECO:0000269|PubMed:19574260,
FT ECO:0000269|PubMed:21633164"
FT /id="VAR_063801"
FT VARIANT 841
FT /note="Q -> P (in COACH1; unknown pathological
FT significance; dbSNP:rs863225234)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063802"
FT VARIANT 843
FT /note="Y -> C (in MKS3; dbSNP:rs386834194)"
FT /evidence="ECO:0000269|PubMed:20232449"
FT /id="VAR_076880"
FT VARIANT 942
FT /note="F -> C (in COACH1; unknown pathological
FT significance; dbSNP:rs863225233)"
FT /evidence="ECO:0000269|PubMed:19574260"
FT /id="VAR_063803"
FT VARIANT 966
FT /note="L -> P (in MKS3; dbSNP:rs386834199)"
FT /evidence="ECO:0000269|PubMed:17377820,
FT ECO:0000269|PubMed:19466712"
FT /id="VAR_062320"
FT CONFLICT 251
FT /note="N -> S (in Ref. 4; BAG52507)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="N -> D (in Ref. 4; BAG52507)"
FT /evidence="ECO:0000305"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 175..180
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 224..229
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 243..255
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 267..277
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 307..310
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 332..337
FT /evidence="ECO:0007829|PDB:7FH1"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 361..365
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 382..388
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 394..402
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 408..412
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 428..431
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 463..467
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 498..502
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 508..514
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 519..548
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 558..591
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 603..632
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 635..641
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 667..679
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 688..700
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 704..708
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 709..712
FT /evidence="ECO:0007829|PDB:7FH1"
FT TURN 729..731
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 732..757
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 762..771
FT /evidence="ECO:0007829|PDB:7FH1"
FT TURN 772..774
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 776..786
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 831..834
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 837..844
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 869..885
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 896..898
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 903..906
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 914..916
FT /evidence="ECO:0007829|PDB:7FH1"
FT STRAND 919..921
FT /evidence="ECO:0007829|PDB:7FH1"
FT TURN 923..925
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 926..929
FT /evidence="ECO:0007829|PDB:7FH1"
FT TURN 930..932
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 936..945
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 947..953
FT /evidence="ECO:0007829|PDB:7FH1"
FT HELIX 958..986
FT /evidence="ECO:0007829|PDB:7FH1"
SQ SEQUENCE 995 AA; 111745 MW; 48B715BDD610C495 CRC64;
MATRGGAGVA MAVWSLLSAR AVTAFLLLFL PRFLQAQTFS FPFQQPEKCD NNQYFDISAL
SCVPCGANQR QDARGTSCVC LPGFQMISNN GGPAIICKKC PENMKGVTED GWNCISCPSD
LTAEGKCHCP IGHILVERDI NGTLLSQATC ELCDGNENSF MVVNALGDRC VRCEPTFVNT
SRSCACSEPN ILTGGLCFSS TGNFPLRRIS AARYGEVGMS LTSEWFAKYL QSSAAACWVY
ANLTSCQALG NMCVMNMNSY DFATFDACGL FQFIFENTAG LSTVHSISFW RQNLPWLFYG
DQLGLAPQVL SSTSLPTNFS FKGENQNTKL KFVAASYDIR GNFLKWQTLE GGVLQLCPDT
ETRLNAAYSF GTTYQQNCEI PISKILIDFP TPIFYDVYLE YTDENQHQYI LAVPVLNLNL
QHNKIFVNQD SNSGKWLLTR RIFLVDAVSG RENDLGTQPR VIRVATQISL SVHLVPNTIN
GNIYPPLITI AYSDIDIKDA NSQSVKVSFS VTYEMDHGEA HVQTDIALGV LGGLAVLASL
LKTAGWKRRI GSPMIDLQTV VKFLVYYAGD LANVFFIITV GTGLYWLIFF KAQKSVSVLL
PMPIQEERFV TYVGCAFALK ALQFLHKLIS QITIDVFFID WERPKGKVLK AVEGEGGVRS
ATVPVSIWRT YFVANEWNEI QTVRKINSLF QVLTVLFFLE VVGFKNLALM DSSSSLSRNP
PSYIAPYSCI LRYAVSAALW LAIGIIQVVF FAVFYERFIE DKIRQFVDLC SMSNISVFLL
SHKCFGYYIH GRSVHGHADT NMEEMNMNLK REAENLCSQR GLVPNTDGQT FEIAISNQMR
QHYDRIHETL IRKNGPARLL SSSASTFEQS IKAYHMMNKF LGSFIDHVHK EMDYFIKDKL
LLERILGMEF MEPMEKSIFY NDEGYSFSSV LYYGNEATLL IFDLLFFCVV DLACQNFILA
SFLTYLQQEI FRYIRNTVGQ KNLASKTLVD QRFLI
