ID MKS1_HUMAN Reviewed; 559 AA. AC Q9NXB0; B7WNX4; F5H885; Q284T0; Q96G13; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 2. DT 27-MAR-2024, entry version 157. DE RecName: Full=Tectonic-like complex member MKS1 {ECO:0000305}; DE AltName: Full=Meckel syndrome type 1 protein; GN Name=MKS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN MKS1. RX PubMed=16415886; DOI=10.1038/ng1714; RA Kyttaelae M., Tallila J., Salonen R., Kopra O., Kohlschmidt N., RA Paavola-Sakki P., Peltonen L., Kestilae M.; RT "MKS1, encoding a component of the flagellar apparatus basal body proteome, RT is mutated in Meckel syndrome."; RL Nat. Genet. 38:155-157(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 86-559 (ISOFORM 1). RC TISSUE=Hepatoma, and Trachea; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Ovary; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-559 (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH TMEM67. 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. RX PubMed=19208769; DOI=10.1242/jcs.028621; RA Bialas N.J., Inglis P.N., Li C., Robinson J.F., Parker J.D., Healey M.P., RA Davis E.E., Inglis C.D., Toivonen T., Cottell D.C., Blacque O.E., RA Quarmby L.M., Katsanis N., Leroux M.R.; RT "Functional interactions between the ciliopathy-associated Meckel syndrome RT 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins."; RL J. Cell Sci. 122:611-624(2009). RN [9] RP INTERACTION WITH FLNA. 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 [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND INTERACTION WITH TMEM107. RX PubMed=26595381; DOI=10.1038/ncb3273; RA Lambacher N.J., Bruel A.L., van Dam T.J., Szymanska K., Slaats G.G., RA Kuhns S., McManus G.J., Kennedy J.E., Gaff K., Wu K.M., van der Lee R., RA Burglen L., Doummar D., Riviere J.B., Faivre L., Attie-Bitach T., RA Saunier S., Curd A., Peckham M., Giles R.H., Johnson C.A., Huynen M.A., RA Thauvin-Robinet C., Blacque O.E.; RT "TMEM107 recruits ciliopathy proteins to subdomains of the ciliary RT transition zone and causes Joubert syndrome."; RL Nat. Cell Biol. 18:122-131(2016). RN [12] RP VARIANTS BBS13 PHE-371 DEL AND TRP-492, AND VARIANTS GLN-123; GLY-286 AND RP THR-450. 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 [13] 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 [14] RP VARIANT MKS1 TRP-166. 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 [15] RP VARIANT JBTS28 SER-362 DEL, AND INVOLVEMENT IN JBTS28. RX PubMed=24886560; DOI=10.1186/1750-1172-9-72; RA Romani M., Micalizzi A., Kraoua I., Dotti M.T., Cavallin M., Sztriha L., RA Ruta R., Mancini F., Mazza T., Castellana S., Hanene B., Carluccio M.A., RA Darra F., Mate A., Zimmermann A., Gouider-Khouja N., Valente E.M.; RT "Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the RT genetic overlap with the lethal ciliopathy Meckel syndrome."; RL Orphanet J. Rare Dis. 9:72-72(2014). RN [16] RP VARIANT CYS-80. RX PubMed=27377014; DOI=10.1016/j.ejmg.2016.06.007; RA Bader I., Decker E., Mayr J.A., Lunzer V., Koch J., Boltshauser E., RA Sperl W., Pietsch P., Ertl-Wagner B., Bolz H., Bergmann C., Rittinger O.; RT "MKS1 mutations cause Joubert syndrome with agenesis of the corpus RT callosum."; RL Eur. J. Med. Genet. 59:386-391(2016). RN [17] RP VARIANTS MKS1 TYR-19; GLU-317; SER-372 DEL; LEU-403 AND SER-421, RP CHARACTERIZATION OF VARIANTS MKS1 TYR-19; GLU-317; SER-372 DEL; LEU-403 AND RP SER-421, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26490104; DOI=10.1136/jmedgenet-2015-103250; RA Slaats G.G., Isabella C.R., Kroes H.Y., Dempsey J.C., Gremmels H., RA Monroe G.R., Phelps I.G., Duran K.J., Adkins J., Kumar S.A., Knutzen D.M., RA Knoers N.V., Mendelsohn N.J., Neubauer D., Mastroyianni S.D., Vogt J., RA Worgan L., Karp N., Bowdin S., Glass I.A., Parisi M.A., Otto E.A., RA Johnson C.A., Hildebrandt F., van Haaften G., Giles R.H., Doherty D.; RT "MKS1 regulates ciliary INPP5E levels in Joubert syndrome."; RL J. Med. Genet. 53:62-72(2016). CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized CC at the transition zone of primary cilia and acting as a barrier that CC prevents diffusion of transmembrane proteins between the cilia and CC plasma membranes. Involved in centrosome migration to the apical cell CC surface during early ciliogenesis. Required for ciliary structure and CC function, including a role in regulating length and appropriate number CC through modulating centrosome duplication. Required for cell branching CC morphology. {ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853, CC ECO:0000269|PubMed:26490104}. CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex) CC (PubMed:26595381). Interacts with TMEM107 (PubMed:26595381). Interacts CC with TCTN3, AHI1, TCTN1, TCTN2, CC2D2A (By similarity). Interacts with CC FLNA (PubMed:22121117). Interacts with TMEM67 (PubMed:17185389). CC Interacts with B9D1 and B9D2 (By similarity). CC {ECO:0000250|UniProtKB:Q5SW45, ECO:0000269|PubMed:17185389, CC ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:26595381}. CC -!- INTERACTION: CC Q9NXB0; Q9BPU9: B9D2; NbExp=8; IntAct=EBI-719269, EBI-6958971; CC Q9NXB0; Q6UX40: TMEM107; NbExp=2; IntAct=EBI-719269, EBI-12845616; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. CC Note=Localizes at the transition zone, a region between the basal body CC and the ciliary axoneme. {ECO:0000269|PubMed:26490104}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9NXB0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NXB0-2; Sequence=VSP_017414; CC Name=3; CC IsoId=Q9NXB0-3; Sequence=VSP_046063; CC -!- DISEASE: Meckel syndrome 1 (MKS1) [MIM:249000]: 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:16415886, CC ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:26490104}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Bardet-Biedl syndrome 13 (BBS13) [MIM:615990]: 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 disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Joubert syndrome 28 (JBTS28) [MIM:617121]: A form of Joubert CC syndrome, a disorder presenting with cerebellar ataxia, oculomotor CC apraxia, hypotonia, neonatal breathing abnormalities and psychomotor CC delay. Neuroradiologically, it is characterized by cerebellar vermian CC hypoplasia/aplasia, thickened and reoriented superior cerebellar CC peduncles, and an abnormally large interpeduncular fossa, giving the CC appearance of a molar tooth on transaxial slices (molar tooth sign). CC Additional variable features include retinal dystrophy, renal disease, CC liver fibrosis, and polydactyly. JBTS28 inheritance is autosomal CC recessive. {ECO:0000269|PubMed:24886560}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH10061.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA91105.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; DQ185029; AAZ94714.1; -; mRNA. DR EMBL; AK000352; BAA91105.1; ALT_INIT; mRNA. DR EMBL; AK310815; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC005962; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010061; AAH10061.1; ALT_INIT; mRNA. DR EMBL; CR457229; CAG33510.1; -; mRNA. DR CCDS; CCDS11603.2; -. [Q9NXB0-1] DR RefSeq; NP_001159399.1; NM_001165927.1. DR RefSeq; NP_001308197.1; NM_001321268.1. DR RefSeq; NP_001308198.1; NM_001321269.1. DR RefSeq; NP_060247.2; NM_017777.3. [Q9NXB0-1] DR RefSeq; XP_016880294.1; XM_017024805.1. DR AlphaFoldDB; Q9NXB0; -. DR BioGRID; 120249; 130. DR ComplexPortal; CPX-2531; MKS transition zone complex. DR CORUM; Q9NXB0; -. DR DIP; DIP-56251N; -. DR IntAct; Q9NXB0; 80. DR STRING; 9606.ENSP00000376827; -. DR TCDB; 8.A.170.1.1; the b9-domain protein complex diffusion barrier for ciliary membrane proteins (cb9db) family. DR iPTMnet; Q9NXB0; -. DR PhosphoSitePlus; Q9NXB0; -. DR BioMuta; MKS1; -. DR DMDM; 92087008; -. DR EPD; Q9NXB0; -. DR MassIVE; Q9NXB0; -. DR MaxQB; Q9NXB0; -. DR PaxDb; 9606-ENSP00000376827; -. DR PeptideAtlas; Q9NXB0; -. DR ProteomicsDB; 27713; -. DR ProteomicsDB; 83068; -. [Q9NXB0-1] DR ProteomicsDB; 83069; -. [Q9NXB0-2] DR Pumba; Q9NXB0; -. DR Antibodypedia; 18351; 118 antibodies from 20 providers. DR DNASU; 54903; -. DR Ensembl; ENST00000393119.7; ENSP00000376827.2; ENSG00000011143.19. [Q9NXB0-1] DR GeneID; 54903; -. DR KEGG; hsa:54903; -. DR MANE-Select; ENST00000393119.7; ENSP00000376827.2; NM_017777.4; NP_060247.2. DR UCSC; uc002ivr.3; human. [Q9NXB0-1] DR AGR; HGNC:7121; -. DR CTD; 54903; -. DR DisGeNET; 54903; -. DR GeneCards; MKS1; -. DR GeneReviews; MKS1; -. DR HGNC; HGNC:7121; MKS1. DR HPA; ENSG00000011143; Low tissue specificity. DR MalaCards; MKS1; -. DR MIM; 249000; phenotype. DR MIM; 609883; gene. DR MIM; 615990; phenotype. DR MIM; 617121; phenotype. DR neXtProt; NX_Q9NXB0; -. DR OpenTargets; ENSG00000011143; -. DR Orphanet; 110; Bardet-Biedl syndrome. DR Orphanet; 475; Joubert syndrome. DR Orphanet; 220493; Joubert syndrome with ocular defect. DR Orphanet; 564; Meckel syndrome. DR PharmGKB; PA30840; -. DR VEuPathDB; HostDB:ENSG00000011143; -. DR eggNOG; KOG4446; Eukaryota. DR GeneTree; ENSGT00510000047471; -. DR HOGENOM; CLU_026711_0_1_1; -. DR InParanoid; Q9NXB0; -. DR OMA; YEHVLCI; -. DR OrthoDB; 318112at2759; -. DR PhylomeDB; Q9NXB0; -. DR TreeFam; TF323812; -. DR PathwayCommons; Q9NXB0; -. DR Reactome; R-HSA-5610787; Hedgehog 'off' state. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR SignaLink; Q9NXB0; -. DR BioGRID-ORCS; 54903; 16 hits in 1151 CRISPR screens. DR ChiTaRS; MKS1; human. DR GeneWiki; MKS1; -. DR GenomeRNAi; 54903; -. DR Pharos; Q9NXB0; Tbio. DR PRO; PR:Q9NXB0; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9NXB0; Protein. DR Bgee; ENSG00000011143; Expressed in right uterine tube and 110 other cell types or tissues. DR ExpressionAtlas; Q9NXB0; baseline and differential. DR GO; GO:0005814; C:centriole; IEA:Ensembl. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; IEA:Ensembl. DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl. DR GO; GO:0060411; P:cardiac septum morphogenesis; IEA:Ensembl. DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:0061009; P:common bile duct development; IEA:Ensembl. DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl. DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl. DR GO; GO:0010669; P:epithelial structure maintenance; IEA:Ensembl. DR GO; GO:0060322; P:head development; IEA:Ensembl. DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IEA:Ensembl. DR GO; GO:0044458; P:motile cilium assembly; IEA:Ensembl. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl. DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:2000095; P:regulation of Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl. DR GO; GO:0003271; P:smoothened signaling pathway involved in regulation of secondary heart field cardioblast proliferation; IEA:Ensembl. DR InterPro; IPR010796; C2_B9-type_dom. DR PANTHER; PTHR12968; B9 DOMAIN-CONTAINING; 1. DR PANTHER; PTHR12968:SF4; MECKEL SYNDROME TYPE 1 PROTEIN; 1. DR Pfam; PF07162; B9-C2; 1. DR PROSITE; PS51381; C2_B9; 1. DR Genevisible; Q9NXB0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Bardet-Biedl syndrome; Cell projection; Ciliopathy; KW Cilium; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; KW Disease variant; Intellectual disability; Joubert syndrome; KW Meckel syndrome; Obesity; Reference proteome. FT CHAIN 1..559 FT /note="Tectonic-like complex member MKS1" FT /id="PRO_0000225686" FT DOMAIN 311..439 FT /note="C2 B9-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00713" FT VAR_SEQ 1..26 FT /note="MAETVWSTDTGEAVYRSRDPVRNLRL -> MAVPVSSFAQRTRSRF (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046063" FT VAR_SEQ 471..559 FT /note="ERLSRFGLRTETTGTVTFRLHCLQQSRAFMESSSLQKRMRSVLDRLEGFSQQ FT SSIHNVLEAFRRARRRMQEARESLPQDLVSPSGTLVS -> LSSSKTKEGRKVDGERVL FT NPQPVSLSLFPGKPHSTAWGLLRLRYELFLSK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017414" FT VARIANT 19 FT /note="D -> Y (in MKS1; no rescue of ciliation defects in FT an MKS1-knockdown cell line; dbSNP:rs863225205)" FT /evidence="ECO:0000269|PubMed:26490104" FT /id="VAR_077515" FT VARIANT 39 FT /note="L -> F (in dbSNP:rs11653070)" FT /id="VAR_060161" FT VARIANT 80 FT /note="W -> C (found in a patient with Joubert syndrome FT also carrying a deletion in MKS1 intron 15 and a missense FT mutation in TCTN3 gene 'P-95'; uncertain significance; FT dbSNP:rs1114167302)" FT /evidence="ECO:0000269|PubMed:27377014" FT /id="VAR_077516" FT VARIANT 123 FT /note="R -> Q (in dbSNP:rs202112856)" FT /evidence="ECO:0000269|PubMed:18327255" FT /id="VAR_062287" FT VARIANT 166 FT /note="R -> W (in MKS1; uncertain significance; FT dbSNP:rs201845154)" FT /evidence="ECO:0000269|PubMed:19466712" FT /id="VAR_062288" FT VARIANT 286 FT /note="D -> G (in dbSNP:rs151023718)" FT /evidence="ECO:0000269|PubMed:18327255" FT /id="VAR_062289" FT VARIANT 317 FT /note="G -> E (in MKS1; uncertain significance; no defect FT of primary cilia formation in starved fibroblasts from a FT patient also carrying a deletion of S-372; no effect on the FT localization to the transition zone; dbSNP:rs863225208)" FT /evidence="ECO:0000269|PubMed:26490104" FT /id="VAR_077517" FT VARIANT 362 FT /note="Missing (in JBTS28)" FT /evidence="ECO:0000269|PubMed:24886560" FT /id="VAR_076978" FT VARIANT 371 FT /note="Missing (in BBS13)" FT /evidence="ECO:0000269|PubMed:18327255" FT /id="VAR_062290" FT VARIANT 372 FT /note="Missing (in MKS1; uncertain significance; no defect FT of primary cilia formation in starved fibroblasts from a FT patient also carrying E-317; no effect on the localization FT to the transition zone)" FT /evidence="ECO:0000269|PubMed:26490104" FT /id="VAR_077518" FT VARIANT 403 FT /note="S -> L (in MKS1; uncertain significance; decreased FT primary cilia formation in starved fibroblasts from a FT patient also carrying a mutation potentially affecting FT splicing; complete rescue of ciliation defects in an FT MKS1-knockdown cell line; no effect on the localization to FT the transition zone; dbSNP:rs773684291)" FT /evidence="ECO:0000269|PubMed:26490104" FT /id="VAR_077519" FT VARIANT 421 FT /note="P -> S (in MKS1; uncertain significance; no effect FT on primary cilia formation in starved fibroblasts from a FT patient also carrying a mutation creating a frameshift and FT a premature stop codon; partial rescue of ciliation defects FT in an MKS1-knockdown cell line; no effect on the FT localization to the transition zone; dbSNP:rs863225210)" FT /evidence="ECO:0000269|PubMed:26490104" FT /id="VAR_077520" FT VARIANT 450 FT /note="I -> T (in dbSNP:rs200865108)" FT /evidence="ECO:0000269|PubMed:18327255" FT /id="VAR_062291" FT VARIANT 492 FT /note="C -> W (in BBS13; dbSNP:rs137853105)" FT /evidence="ECO:0000269|PubMed:18327255" FT /id="VAR_062292" SQ SEQUENCE 559 AA; 64528 MW; 3E4EBFDAFA8FB39D CRC64; MAETVWSTDT GEAVYRSRDP VRNLRLRVHL QRITSSNFLH YQPAAELGKD LIDLATFRPQ PTASGHRPEE DEEEEIVIGW QEKLFSQFEV DLYQNETACQ SPLDYQYRQE ILKLENSGGK KNRRIFTYTD SDRYTNLEEH CQRMTTAASE VPSFLVERMA NVRRRRQDRR GMEGGILKSR IVTWEPSEEF VRNNHVINTP LQTMHIMADL GPYKKLGYKK YEHVLCTLKV DSNGVITVKP DFTGLKGPYR IETEGEKQEL WKYTIDNVSP HAQPEEEERE RRVFKDLYGR HKEYLSSLVG TDFEMTVPGA LRLFVNGEVV SAQGYEYDNL YVHFFVELPT AHWSSPAFQQ LSGVTQTCTT KSLAMDKVAH FSYPFTFEAF FLHEDESSDA LPEWPVLYCE VLSLDFWQRY RVEGYGAVVL PATPGSHTLT VSTWRPVELG TVAELRRFFI GGSLELEDLS YVRIPGSFKG ERLSRFGLRT ETTGTVTFRL HCLQQSRAFM ESSSLQKRMR SVLDRLEGFS QQSSIHNVLE AFRRARRRMQ EARESLPQDL VSPSGTLVS //