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 27-MAR-2024, entry version 172. 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 STRUCTURE BY ELECTRON MICROSCOPY (3.34 ANGSTROMS), TOPOLOGY, REGION, COILED RP COIL, DISULFIDE BONDS, SUBUNIT, GLYCOSYLATION AT ASN-141; ASN-179; ASN-242 RP AND ASN-318, AND INTERACTION WITH WNT5A. RX PubMed=34731008; DOI=10.1126/sciadv.abj9748; RA Liu D., Qian D., Shen H., Gong D.; RT "Structure of the human Meckel-Gruber protein Meckelin."; RL Sci. Adv. 7:eabj9748-eabj9748(2021). RN [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] RP VARIANTS COACH1 ASN-99; ARG-130; GLN-172; SER-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 [23] 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 [24] 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 [25] RP CHARACTERIZATION OF VARIANTS MKS3 THR-252; SER-349; PRO-376; GLN-440; RP CYS-549 AND ARG-615, INTERACTION WITH WNT5A AND ROR2, AND FUNCTION. RX PubMed=26035863; DOI=10.1242/dmm.019083; RA Abdelhamed Z.A., Natarajan S., Wheway G., Inglehearn C.F., Toomes C., RA Johnson C.A., Jagger D.J.; RT "The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning RT and epithelial branching morphogenesis in mice via the non-canonical Wnt RT pathway."; RL Dis. Model. Mech. 8:527-541(2015). RN [26] RP VARIANT MKS3 CYS-549. RX PubMed=26191240; RA Zhang M., Cheng J., Liu A., Wang L., Xiong L., Chen M., Sun Y., Li J., RA Lu Y., Yuan H., Li Y., Lu Y.; RT "A missense mutation in TMEM67 causes Meckel-Gruber syndrome type 3 (MKS3): RT a family from China."; RL Int. J. Clin. Exp. Pathol. 8:5379-5386(2015). RN [27] 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 [28] 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). RN [29] RP VARIANT MKS3 ALA-786. RX PubMed=31411728; DOI=10.1111/cge.13623; RA Radhakrishnan P., Nayak S.S., Shukla A., Lindstrand A., Girisha K.M.; RT "Meckel syndrome: Clinical and mutation profile in six fetuses."; RL Clin. Genet. 96:560-565(2019). RN [30] RP VARIANT JBTS6 SER-242. RX PubMed=32000717; DOI=10.1186/s12881-020-0962-0; RA Bui T.P.H., Nguyen N.T., Ngo V.D., Nguyen H.N., Ly T.T.H., Do H.D., RA Huynh M.T.; RT "Novel compound heterozygous TMEM67 variants in a Vietnamese family with RT Joubert syndrome: a case report."; RL BMC Med. Genet. 21:18-18(2020). RN [31] RP CHARACTERIZATION OF VARIANT GLU-359, CHARACTERIZATION OF VARIANT COACH1 RP ARG-782, CHARACTERIZATION OF VARIANTS MKS3 PRO-376 AND GLU-786, AND RP MUTAGENESIS OF CYS-170; THR-176; HIS-790 AND GLY-979. RX PubMed=34964473; DOI=10.1093/hmg/ddab344; RA Lange K.I., Best S., Tsiropoulou S., Berry I., Johnson C.A., Blacque O.E.; RT "Interpreting ciliopathy-associated missense variants of uncertain RT significance (VUS) in Caenorhabditis elegans."; RL Hum. Mol. Genet. 31:1574-1587(2022). 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. Is a key regulator of stereociliary bundle orientation (By CC similarity). Required for epithelial cell branching morphology. CC Essential for endoplasmic reticulum-associated degradation (ERAD) of CC surfactant protein C (SFTPC). Involved in the negative regulation of CC canonical Wnt signaling, and activation of the non-canonical cascade CC stimulated by WNT5A (PubMed:26035863). In non-canonical Wnt signaling, CC it may act as ROR2 coreceptor (By similarity). CC {ECO:0000250|UniProtKB:Q8BR76, ECO:0000269|PubMed:17185389, CC ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:19596800, CC ECO:0000269|PubMed:19815549, ECO:0000269|PubMed:26035863}. CC -!- SUBUNIT: Homodimer (PubMed:34731008). Part of the tectonic-like complex CC (also named B9 complex) (By similarity). Interacts with DNAJB9, DNAJC10 CC and mutated SFTPC. Interacts with SYNE2 during the early establishment CC of cell polarity. Interacts (via C-terminus) with FLNA. Interacts with CC TMEM218 (PubMed:35137054). Interacts with WNT5A (PubMed:34731008, CC PubMed:26035863). Interacts with ROR2 (PubMed:26035863). CC {ECO:0000250|UniProtKB:Q8BR76, ECO:0000269|PubMed:17185389, CC ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:19815549, CC ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:26035863, CC ECO:0000269|PubMed:34731008, 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, CC ECO:0000269|PubMed:26035863, ECO:0000269|PubMed:26191240, CC ECO:0000269|PubMed:31411728, ECO:0000269|PubMed:34964473}. 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, ECO:0000269|PubMed:32000717}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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, ECO:0000269|PubMed:34964473}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms 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 RefSeq; NP_001135773.1; NM_001142301.1. DR RefSeq; NP_714915.3; NM_153704.5. DR PDB; 7FH1; EM; 3.34 A; A/B=1-995. DR PDBsum; 7FH1; -. DR AlphaFoldDB; Q5HYA8; -. DR EMDB; EMD-31584; -. DR SMR; Q5HYA8; -. DR BioGRID; 124799; 148. DR ComplexPortal; CPX-2531; MKS transition zone complex. 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 GlyCosmos; Q5HYA8; 1 site, No reported glycans. DR GlyGen; Q5HYA8; 4 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; 9606-ENSP00000389998; -. DR PeptideAtlas; Q5HYA8; -. DR ProteomicsDB; 33938; -. DR Pumba; Q5HYA8; -. DR Antibodypedia; 25725; 111 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 KEGG; hsa:91147; -. DR MANE-Select; ENST00000453321.8; ENSP00000389998.3; NM_153704.6; NP_714915.3. DR UCSC; uc003yga.5; human. DR AGR; HGNC:28396; -. DR CTD; 91147; -. DR DisGeNET; 91147; -. DR GeneCards; TMEM67; -. DR GeneReviews; TMEM67; -. DR HGNC; HGNC:28396; TMEM67. DR HPA; ENSG00000164953; Tissue enhanced (heart). 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; DKQAYII; -. DR OrthoDB; 177595at2759; -. 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 1155 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 138 other cell types or tissues. DR ExpressionAtlas; Q5HYA8; baseline and differential. 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: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:0035567; P:non-canonical Wnt signaling pathway; 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:SF2; MECKELIN; 1. DR PANTHER; PTHR21274; UNCHARACTERIZED; 1. DR Pfam; PF09773; Meckelin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR Genevisible; Q5HYA8; HS. PE 1: Evidence at protein level; KW 3D-structure; Bardet-Biedl syndrome; Cell membrane; Cell projection; KW Ciliopathy; Cilium; Cilium biogenesis/degradation; Coiled coil; Cytoplasm; KW Cytoskeleton; Deafness; Disease variant; Disulfide bond; KW Endoplasmic reticulum; Glycoprotein; Intellectual disability; KW Joubert syndrome; Meckel syndrome; Membrane; Nephronophthisis; Obesity; KW Reference proteome; Retinitis pigmentosa; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..36 FT /evidence="ECO:0000255" FT CHAIN 37..995 FT /note="Meckelin" FT /id="PRO_0000225689" FT TOPO_DOM 37..519 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 520..548 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 549..558 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 559..590 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 591..603 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 604..631 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 632..670 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 671..701 FT /note="Discontinuously helical; Name=4" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 671..679 FT /note="Helical; Name=4A" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 680..688 FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 689..701 FT /note="Helical; Name=4B" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 702..731 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 732..771 FT /note="Discontinuously helical; Name=5" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 732..757 FT /note="Helical; Name=5A" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 758..762 FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 763..771 FT /note="Helical; Name=5B" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 772..926 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 927..952 FT /note="Discontinuously helical; Name=6" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 927..929 FT /note="Helical; Name=6A" FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 930..936 FT /evidence="ECO:0000269|PubMed:34731008" FT INTRAMEM 937..952 FT /note="Helical; Name=6B" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 953..957 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:34731008" FT TRANSMEM 958..985 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:34731008" FT TOPO_DOM 986..995 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:34731008" FT REGION 37..280 FT /note="Cysteine-rich" FT /evidence="ECO:0000269|PubMed:34731008" FT COILED 828..917 FT /evidence="ECO:0000269|PubMed:34731008" FT CARBOHYD 141 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT CARBOHYD 179 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT CARBOHYD 242 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT CARBOHYD 318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 49..62 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 65..78 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 80..97 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 100..114 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 117..127 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 129..150 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 153..170 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 173..184 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 186..197 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 237..246 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 253..268 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" FT DISULFID 357..378 FT /evidence="ECO:0000269|PubMed:34731008, FT ECO:0007744|PDB:7FH1" 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; uncertain significance; FT dbSNP:rs386834188)" FT /evidence="ECO:0000269|PubMed:19466712" FT /id="VAR_062310" FT VARIANT 82 FT /note="P -> R (in JBTS6; uncertain significance; FT dbSNP:rs772437766)" FT /evidence="ECO:0000269|PubMed:19574260" FT /id="VAR_063783" FT VARIANT 82 FT /note="P -> S (in JBTS6; uncertain significance; FT dbSNP:rs762543032)" FT /evidence="ECO:0000269|PubMed:19574260" FT /id="VAR_063784" FT VARIANT 90 FT /note="N -> K (found in Joubert syndrome-related disorder; FT likely pathogenic)" FT /evidence="ECO:0000269|PubMed:20232449" FT /id="VAR_076871" FT VARIANT 99 FT /note="K -> N (in COACH1; uncertain significance; FT dbSNP:rs797046045)" FT /evidence="ECO:0000269|PubMed:19574260" FT /id="VAR_063785" FT VARIANT 124 FT /note="E -> K (found in Joubert syndrome-related disorder; FT likely pathogenic; 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; uncertain significance; FT 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 -> S (in COACH1 and JBTS6)" FT /evidence="ECO:0000269|PubMed:19574260, FT ECO:0000269|PubMed:32000717" FT /id="VAR_063788" FT VARIANT 245 FT /note="S -> F (in MKS3; uncertain 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; loss of FT interaction with WNT5A; dbSNP:rs202149403)" FT /evidence="ECO:0000269|PubMed:17377820, FT ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:19508969, FT ECO:0000269|PubMed:19574260, ECO:0000269|PubMed:26035863" FT /id="VAR_062313" FT VARIANT 257 FT /note="M -> V (in COACH1; uncertain significance; FT 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; uncertain significance; FT dbSNP:rs386834208)" FT /id="VAR_062315" FT VARIANT 301 FT /note="D -> E (found in Joubert syndrome-related disorder; FT likely pathogenic; 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; loss of interaction with FT WNT5A; dbSNP:rs386834180)" FT /evidence="ECO:0000269|PubMed:19574260, FT ECO:0000269|PubMed:20232449, ECO:0000269|PubMed:26035863" 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 359 FT /note="D -> E (does not affect Wnt signaling regulation; FT when expressed in TMEM67-null cells it induces ROR2 FT phosphorylation upon stimulation by WNT5A)" FT /evidence="ECO:0000269|PubMed:34964473" FT /id="VAR_087308" 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; 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 decreased function in non-canonical Wnt signaling FT activation; when expressed in TMEM67-null cells does not FT induce ROR2 phosphorylation upon stimulation by WNT5A; loss FT of interaction with WNT5A; dbSNP:rs137853106)" FT /evidence="ECO:0000269|PubMed:16415887, FT ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:26035863, FT ECO:0000269|PubMed:34964473" 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; loss of interaction with FT WNT5A; affects Wnt signaling regulation; when expressed in FT TMEM67-null cells does not rescue increased canonical Wnt FT signaling; dbSNP:rs386834182)" FT /evidence="ECO:0000269|PubMed:17377820, FT ECO:0000269|PubMed:19058225, ECO:0000269|PubMed:19466712, FT ECO:0000269|PubMed:26035863" FT /id="VAR_062318" FT VARIANT 441 FT /note="R -> C (in COACH1; uncertain significance; FT 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; uncertain significance; FT 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 549 FT /note="R -> C (in MKS3; affects Wnt signaling regulation; FT when expressed in TMEM67-null cells does not rescue FT increased canonical Wnt signaling)" FT /evidence="ECO:0000269|PubMed:26035863, FT ECO:0000269|PubMed:26191240" FT /id="VAR_087309" FT VARIANT 569 FT /note="G -> D (found in Joubert syndrome-related disorder; FT likely pathogenic; 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; affects Wnt FT signaling regulation; when expressed in TMEM67-null cells FT does not rescue increased canonical Wnt signaling; FT dbSNP:rs201893408)" FT /evidence="ECO:0000269|PubMed:19466712, FT ECO:0000269|PubMed:19508969, ECO:0000269|PubMed:19574260, FT ECO:0000269|PubMed:26035863" FT /id="VAR_062319" FT VARIANT 616 FT /note="A -> V (found in Joubert syndrome-related disorder; FT likely pathogenic; dbSNP:rs757204749)" FT /evidence="ECO:0000269|PubMed:20232449" FT /id="VAR_076876" FT VARIANT 637 FT /note="F -> L (in COACH1; uncertain significance; FT 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 (found in Joubert syndrome-related disorder; FT likely pathogenic)" FT /evidence="ECO:0000269|PubMed:20232449" FT /id="VAR_076878" FT VARIANT 782 FT /note="H -> R (in COACH1; decreased function in FT non-canonical Wnt signaling activation; when expressed in FT TMEM67-null cells does not induce ROR2 phosphorylation upon FT stimulation by WNT5A; dbSNP:rs777137476)" FT /evidence="ECO:0000269|PubMed:19058225, FT ECO:0000269|PubMed:34964473" FT /id="VAR_063799" FT VARIANT 786 FT /note="G -> A (in MKS3)" FT /evidence="ECO:0000269|PubMed:31411728" FT /id="VAR_087310" FT VARIANT 786 FT /note="G -> E (in MKS3; decreased function in non-canonical FT Wnt signaling activation; when expressed in TMEM67-null FT cells does not induce ROR2 phosphorylation upon stimulation FT by WNT5A; dbSNP:rs386834193)" FT /evidence="ECO:0000269|PubMed:20232449, FT ECO:0000269|PubMed:34964473" 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; uncertain significance; FT 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; uncertain significance; FT 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 MUTAGEN 170 FT /note="C->Y: Decreased function in non-canonical Wnt FT signaling activation. When expressed in TMEM67-null cells FT does not induce ROR2 phosphorylation upon stimulation by FT WNT5A." FT /evidence="ECO:0000269|PubMed:34964473" FT MUTAGEN 176 FT /note="T->I: Does not affect function in non-canonical Wnt FT signaling activation. When expressed in TMEM67-null cells FT it induces ROR2 phosphorylation upon stimulation by WNT5A." FT /evidence="ECO:0000269|PubMed:34964473" FT MUTAGEN 790 FT /note="H->R: Decreased function in non-canonical Wnt FT signaling activation. When expressed in TMEM67-null cells FT does not induce ROR2 phosphorylation upon stimulation by FT WNT5A." FT /evidence="ECO:0000269|PubMed:34964473" FT MUTAGEN 979 FT /note="G->R: Does not affect function in non-canonical Wnt FT signaling activation. When expressed in TMEM67-null cells FT it induces ROR2 phosphorylation upon stimulation by WNT5A." FT /evidence="ECO:0000269|PubMed:34964473" 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 //