ID CXA1_HUMAN Reviewed; 382 AA. AC P17302; B2R5U9; Q6FHU1; Q9Y5I8; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 04-NOV-2026, entry version 271. DE RecName: Full=Gap junction alpha-1 protein; DE AltName: Full=Connexin-43; DE Short=Cx43; DE AltName: Full=Gap junction 43 kDa heart protein; GN Name=GJA1; Synonyms=GJAL; 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]. RC TISSUE=Heart muscle; RX PubMed=1696265; DOI=10.1083/jcb.111.2.589; RA Fishman G.I., Spray D.C., Leinwand L.A.; RT "Molecular characterization and functional expression of the human cardiac RT gap junction channel."; RL J. Cell Biol. 111:589-598(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1646158; DOI=10.1016/0888-7543(91)90507-b; RA Fishman G.I., Eddy R.L., Shows T.B., Rosenthal L., Leinwand L.A.; RT "The human connexin gene family of gap junction proteins: distinct RT chromosomal locations but similar structures."; RL Genomics 10:250-256(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10581143; DOI=10.1053/euhj.1999.1718; RA Haefliger J.-A., Goy J.J., Waeber G.; RT "Sporadic cases of dilated cardiomyopathies associated with RT atrioventricular conduction defects are not linked to mutation within the RT connexins 40 and 43 genes."; RL Eur. Heart J. 20:1843-1843(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [9] RP DISULFIDE BONDS. RX PubMed=9430691; DOI=10.1074/jbc.273.3.1519; RA Toyofuku T., Yabuki M., Otsu K., Kuzuya T., Hori M., Tada M.; RT "Intercellular calcium signaling via gap junction in connexin-43- RT transfected cells."; RL J. Biol. Chem. 273:1519-1528(1998). RN [10] RP INTERACTION WITH NOV. RX PubMed=15181016; DOI=10.1074/jbc.m404073200; RA Gellhaus A., Dong X., Propson S., Maass K., Klein-Hitpass L., Kibschull M., RA Traub O., Willecke K., Perbal B., Lye S.J., Winterhager E.; RT "Connexin43 interacts with NOV: a possible mechanism for negative RT regulation of cell growth in choriocarcinoma cells."; RL J. Biol. Chem. 279:36931-36942(2004). RN [11] RP INTERACTION WITH NOV. RX PubMed=15213231; DOI=10.1074/jbc.m403952200; RA Fu C.T., Bechberger J.F., Ozog M.A., Perbal B., Naus C.C.; RT "CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible RT mechanism of connexin-mediated growth suppression."; RL J. Biol. Chem. 279:36943-36950(2004). RN [12] RP PHOSPHORYLATION AT SER-262. RX PubMed=14702389; DOI=10.1242/jcs.00889; RA Doble B.W., Dang X., Ping P., Fandrich R.R., Nickel B.E., Jin Y., RA Cattini P.A., Kardami E.; RT "Phosphorylation of serine 262 in the gap junction protein connexin-43 RT regulates DNA synthesis in cell-cell contact forming cardiomyocytes."; RL J. Cell Sci. 117:507-514(2004). RN [13] RP REVIEW. RX PubMed=10764404; DOI=10.1161/01.res.86.7.723; RA Saffitz J.E., Laing J.G., Yamada K.A.; RT "Connexin expression and turnover: implications for cardiac excitability."; RL Circ. Res. 86:723-728(2000). RN [14] RP SHOWS THAT HEART LATERALIZATION DEFECT ARE NOT DUE TO GJA1. RX PubMed=8873667; DOI=10.1161/01.cir.94.8.1909; RA Gebbia M., Towbin J.A., Casey B.; RT "Failure to detect connexin43 mutations in 38 cases of sporadic and RT familial heterotaxy."; RL Circulation 94:1909-1912(1996). RN [15] RP SHOWS THAT HEART LATERALIZATION DEFECTS ARE NOT DUE TO GJA1. RX PubMed=9155619; DOI=10.1136/hrt.77.4.369; RA Penman Splitt M., Tsai M.Y., Burn J., Goodship J.A.; RT "Absence of mutations in the regulatory domain of the gap junction protein RT connexin 43 in patients with visceroatrial heterotaxy."; RL Heart 77:369-370(1997). RN [16] RP SHOWS THAT HEART LATERALIZATION DEFECTS ARE NOT DUE TO GJA1. RX PubMed=9443444; DOI=10.1161/01.cir.97.1.117; RA Toth T., Hajdu J., Marton T., Nagy B., Papp Z.; RT "Connexin43 gene mutations and heterotaxy."; RL Circulation 97:117-118(1998). RN [17] RP ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, TISSUE RP SPECIFICITY, AND FUNCTION. RX PubMed=11741837; DOI=10.1093/hmg/10.25.2945; RA Liu X.Z., Xia X.J., Adams J., Chen Z.Y., Welch K.O., Tekin M., Ouyang X.M., RA Kristiansen A., Pandya A., Balkany T., Arnos K.S., Nance W.E.; RT "Mutations in GJA1 (connexin 43) are associated with non-syndromic RT autosomal recessive deafness."; RL Hum. Mol. Genet. 10:2945-2951(2001). RN [18] RP PHOSPHORYLATION AT SER-325; SER-328 AND SER-330 BY CSNK1D/CK1, AND RP INTERACTION WITH CSNK1D. RX PubMed=12270943; DOI=10.1074/jbc.m209427200; RA Cooper C.D., Lampe P.D.; RT "Casein kinase 1 regulates connexin-43 gap junction assembly."; RL J. Biol. Chem. 277:44962-44968(2002). RN [19] RP INTERACTION WITH RIC1. RX PubMed=16112082; DOI=10.1016/j.bbrc.2005.08.019; RA Akiyama M., Ishida N., Ogawa T., Yogo K., Takeya T.; RT "Molecular cloning and functional analysis of a novel Cx43 partner protein RT CIP150."; RL Biochem. Biophys. Res. Commun. 335:1264-1271(2005). RN [20] RP PHOSPHORYLATION AT SER-255 AND SER-262. RX PubMed=15605363; DOI=10.1002/mc.20072; RA Arnold J.M., Phipps M.W., Chen J., Phipps J.; RT "Cellular sublocalization of Cx43 and the establishment of functional RT coupling in IMR-32 neuroblastoma cells."; RL Mol. Carcinog. 42:159-169(2005). RN [21] RP INVOLVEMENT IN ODDD-AR. RX PubMed=16816024; DOI=10.1136/jmg.2005.037655; RA Richardson R.J., Joss S., Tomkin S., Ahmed M., Sheridan E., Dixon M.J.; RT "A nonsense mutation in the first transmembrane domain of connexin 43 RT underlies autosomal recessive oculodentodigital syndrome."; RL J. Med. Genet. 43:E37-E37(2006). RN [22] RP NON-ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, VARIANTS RP ODDD SER-17; PRO-18; ARG-21; GLU-22; THR-23; VAL-40; LYS-49; PHE-52 INS; RP SER-76; VAL-90; CYS-98; ASN-102; THR-130; GLU-134; ARG-138; HIS-202 AND RP LEU-216, AND VARIANT VAL-253. RX PubMed=12457340; DOI=10.1086/346090; RA Paznekas W.A., Boyadjiev S.A., Shapiro R.E., Daniels O., Wollnik B., RA Keegan C.E., Innis J.W., Dinulos M.B., Christian C., Hannibal M.C., RA Jabs E.W.; RT "Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of RT oculodentodigital dysplasia."; RL Am. J. Hum. Genet. 72:408-418(2003). RN [23] RP TISSUE SPECIFICITY. RX PubMed=18662195; DOI=10.1111/j.1582-4934.2008.00438.x; RA Fidler L.M., Wilson G.J., Liu F., Cui X., Scherer S.W., Taylor G.P., RA Hamilton R.M.; RT "Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy RT caused by plakophilin-2 mutations."; RL J. Cell. Mol. Med. 13:4219-4228(2009). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255; SER-314 AND SER-344, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [25] RP SUMOYLATION AT LYS-144 AND LYS-237, AND SUBCELLULAR LOCATION. RX PubMed=22411987; DOI=10.1074/jbc.m111.281832; RA Kjenseth A., Fykerud T.A., Sirnes S., Bruun J., Yohannes Z., Kolberg M., RA Omori Y., Rivedal E., Leithe E.; RT "The gap junction channel protein connexin 43 is covalently modified and RT regulated by SUMOylation."; RL J. Biol. Chem. 287:15851-15861(2012). RN [26] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=24077100; DOI=10.1038/nature12640; RA Ablasser A., Schmid-Burgk J.L., Hemmerling I., Horvath G.L., Schmidt T., RA Latz E., Hornung V.; RT "Cell intrinsic immunity spreads to bystander cells via the intercellular RT transfer of cGAMP."; RL Nature 503:530-534(2013). RN [27] RP SUBCELLULAR LOCATION. RX PubMed=25225338; DOI=10.1083/jcb.201312110; RA Patel D.M., Dubash A.D., Kreitzer G., Green K.J.; RT "Disease mutations in desmoplakin inhibit Cx43 membrane targeting mediated RT by desmoplakin-EB1 interactions."; RL J. Cell Biol. 206:779-797(2014). RN [28] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=26604139; DOI=10.1093/hmg/ddv481; RA Boyden L.M., Kam C.Y., Hernandez-Martin A., Zhou J., Craiglow B.G., RA Sidbury R., Mathes E.F., Maguiness S.M., Crumrine D.A., Williams M.L., RA Hu R., Lifton R.P., Elias P.M., Green K.J., Choate K.A.; RT "Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy RT syndrome."; RL Hum. Mol. Genet. 25:348-357(2016). RN [29] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=31992625; DOI=10.1128/mbio.03187-19; RA Pepin G., De Nardo D., Rootes C.L., Ullah T.R., Al-Asmari S.S., Balka K.R., RA Li H.M., Quinn K.M., Moghaddas F., Chappaz S., Kile B.T., Morand E.F., RA Masters S.L., Stewart C.R., Williams B.R.G., Gantier M.P.; RT "Connexin-Dependent Transfer of cGAMP to Phagocytes Modulates Antiviral RT Responses."; RL MBio 11:0-0(2020). RN [30] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=34905516; DOI=10.1172/jci144363; RA Godsel L.M., Roth-Carter Q.R., Koetsier J.L., Tsoi L.C., Huffine A.L., RA Broussard J.A., Fitz G.N., Lloyd S.M., Kweon J., Burks H.E., Hegazy M., RA Amagai S., Harms P.W., Xing X., Kirma J., Johnson J.L., Urciuoli G., RA Doglio L.T., Swindell W.R., Awatramani R., Sprecher E., Bao X., RA Cohen-Barak E., Missero C., Gudjonsson J.E., Green K.J.; RT "Translational implications of Th17-skewed inflammation due to genetic RT deficiency of a cadherin stress sensor."; RL J. Clin. Invest. 132:0-0(2022). RN [31] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=38375917; DOI=10.1111/pace.14950; RA Blich M., Zohar Y., Cohen-Kaplan V., Minkov I., Asleh R., RA Horowitz-Cederboim S., Weiss K., Paperna T., Lessick J., Abadi S., RA Khoury A., Gepstein L., Suleiman M., Caspi O.; RT "Ser194Leu DSG2 mutation, associated with arrhythmogenic left ventricular RT cardiomyopathy and ventricular tachycardia."; RL Pacing Clin. Electrophysiol. 47:503-510(2024). RN [32] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=40010341; DOI=10.1016/j.immuni.2025.01.016; RA Huai W., Yang K., Xing C., Song K., Lyu H., Williams N.S., Wu J., Yan N.; RT "OAS cross-activates RNase L intercellularly through cell-to-cell transfer RT of 2-5A to spread innate immunity."; RL Immunity 58:797-810.e6(2025). RN [33] RP INVOLVEMENT IN PPKCA1, VARIANT PPKCA1 VAL-8, AND CHARACTERIZATION OF RP VARIANT PPKCA1 VAL-8. RX PubMed=25168385; DOI=10.1093/hmg/ddu442; RA Wang H., Cao X., Lin Z., Lee M., Jia X., Ren Y., Dai L., Guan L., Zhang J., RA Lin X., Zhang J., Chen Q., Feng C., Zhou E.Y., Yin J., Xu G., Yang Y.; RT "Exome sequencing reveals mutation in GJA1 as a cause of keratoderma- RT hypotrichosis-leukonychia totalis syndrome."; RL Hum. Mol. Genet. 24:243-250(2015). RN [34] RP INVOLVEMENT IN EKVP3, VARIANTS EKVP3 VAL-44 AND ASP-227, CHARACTERIZATION RP OF VARIANTS EKVP3 VAL-44 AND ASP-227, AND SUBCELLULAR LOCATION. RX PubMed=25398053; DOI=10.1038/jid.2014.485; RG Yale Center for Mendelian Genomics; RA Boyden L.M., Craiglow B.G., Zhou J., Hu R., Loring E.C., Morel K.D., RA Lauren C.T., Lifton R.P., Bilguvar K., Paller A.S., Choate K.A.; RT "Dominant de novo mutations in GJA1 cause erythrokeratodermia variabilis et RT progressiva, without features of oculodentodigital dysplasia."; RL J. Invest. Dermatol. 135:1540-1547(2015). RN [35] RP VARIANTS HEART MALFORMATIONS GLY-352; PRO-364 AND ASN-365, VARIANTS ALA-326 RP AND GLY-373, AND CHARACTERIZATION OF VARIANT HEART MALFORMATIONS PRO-364. RX PubMed=7715640; DOI=10.1056/nejm199505183322002; RA Britz-Cunningham S.H., Shah M.M., Zuppan C.W., Fletcher W.H.; RT "Mutations of the connexin43 gap-junction gene in patients with heart RT malformations and defects of laterality."; RL N. Engl. J. Med. 332:1323-1329(1995). RN [36] RP VARIANTS HLHS1 GLN-362 AND GLN-376, AND CHARACTERIZATION OF VARIANTS HLHS1 RP GLN-362 AND GLN-376. RX PubMed=11470490; DOI=10.1016/s0027-5107(01)00160-9; RA Dasgupta C., Martinez A.-M., Zuppan C.W., Shah M.M., Bailey L.L., RA Fletcher W.H.; RT "Identification of connexin43 (alpha1) gap junction gene mutations in RT patients with hypoplastic left heart syndrome by denaturing gradient gel RT electrophoresis (DGGE)."; RL Mutat. Res. 479:173-186(2001). RN [37] RP VARIANT ODDD MET-96. RX PubMed=15108203; DOI=10.1002/ajmg.a.20614; RA Kjaer K.W., Hansen L., Eiberg H., Leicht P., Opitz J.M., Tommerup N.; RT "Novel Connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia RT with curly hair."; RL Am. J. Med. Genet. A 127:152-157(2004). RN [38] RP VARIANT HSS HIS-76. RX PubMed=14974090; DOI=10.1002/humu.9220; RA Pizzuti A., Flex E., Mingarelli R., Salpietro C., Zelante L., RA Dallapiccola B.; RT "A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum RT phenotype."; RL Hum. Mutat. 23:286-286(2004). RN [39] RP VARIANTS ODDD PRO-27; MET-31; VAL-40; TYR-69; PRO-113; ASN-134; GLN-148 AND RP HIS-202, AND VARIANT SDTY3 SER-143. RX PubMed=14729836; DOI=10.1136/jmg.2003.012005; RA Richardson R.R., Donnai D., Meire F., Dixon M.J.; RT "Expression of Gja1 correlates with the phenotype observed in RT oculodentodigital syndrome/type III syndactyly."; RL J. Med. Genet. 41:60-67(2004). RN [40] RP VARIANT ODDD PRO-194. RX PubMed=15637728; DOI=10.1002/ajmg.a.30554; RA Vitiello C., D'Adamo P., Gentile F., Vingolo E.M., Gasparini P., Banfi S.; RT "A novel GJA1 mutation causes oculodentodigital dysplasia without RT syndactyly."; RL Am. J. Med. Genet. A 133:58-60(2005). RN [41] RP VARIANT ODDD ARG-95. RX PubMed=16222672; DOI=10.1002/ajmg.a.30925; RA Honkaniemi J., Kalkkila J.P., Koivisto P., Kahara V., Latvala T., RA Simola K.; RT "Letter to the editor: Novel GJA1 mutation in oculodentodigital RT dysplasia."; RL Am. J. Med. Genet. A 139:48-49(2005). RN [42] RP VARIANT ODDD HIS-59. RX PubMed=16219735; DOI=10.1001/archopht.123.10.1422; RA Vasconcellos J.P.C., Melo M.B., Schimiti R.B., Bressanim N.C., Costa F.F., RA Costa V.P.; RT "A novel mutation in the GJA1 gene in a family with oculodentodigital RT dysplasia."; RL Arch. Ophthalmol. 123:1422-1426(2005). RN [43] RP VARIANTS CONGENITAL HEART MALFORMATIONS TRP-239; THR-251; PRO-253; LEU-283 RP AND ASN-290. RX PubMed=15978203; RA Chen P., Xie L.-J., Huang G.-Y., Zhao X.-Q., Chang C.; RT "Mutations of connexin43 in fetuses with congenital heart malformations."; RL Chin. Med. J. 118:971-976(2005). RN [44] RP VARIANT LEU-41. RX PubMed=15757815; RA Kellermayer R., Keller M., Ratajczak P., Richardson E., Harangi F., RA Merei E., Melegh B., Kosztolanyi G., Richard G.; RT "Bigenic connexin mutations in a patient with hidrotic ectodermal RT dysplasia."; RL Eur. J. Dermatol. 15:75-79(2005). RN [45] RP VARIANTS ODDD VAL-40; ASP-110; THR-147 AND PHE-169 DEL. RX PubMed=16378922; DOI=10.1016/j.ejmg.2005.05.003; RA Debeer P., Van Esch H., Huysmans C., Pijkels E., De Smet L., Van de Ven W., RA Devriendt K., Fryns J.-P.; RT "Novel GJA1 mutations in patients with oculo-dento-digital dysplasia RT (ODDD)."; RL Eur. J. Med. Genet. 48:377-387(2005). RN [46] RP VARIANTS ODDD GLU-96; PRO-113; ASN-154 AND TYR-220. RX PubMed=16813608; DOI=10.1111/j.1399-0004.2006.00631.x; RA Wiest T., Herrmann O., Stoegbauer F., Grasshoff U., Enders H., Koch M.J., RA Grond-Ginsbach C., Schwaninger M.; RT "Clinical and genetic variability of oculodentodigital dysplasia."; RL Clin. Genet. 70:71-72(2006). RN [47] RP VARIANT ODDD PRO-11. RX PubMed=16709485; RA Kelly S.C., Ratajczak P., Keller M., Purcell S.M., Griffin T., Richard G.; RT "A novel GJA 1 mutation in oculo-dento-digital dysplasia with curly hair RT and hyperkeratosis."; RL Eur. J. Dermatol. 16:241-245(2006). RN [48] RP VARIANT ODDD ALA-154. RX PubMed=17509830; DOI=10.1016/j.ijom.2007.03.004; RA van Es R.J.J., Wittebol-Post D., Beemer F.A.; RT "Oculodentodigital dysplasia with mandibular retrognathism and absence of RT syndactyly: a case report with a novel mutation in the connexin 43 gene."; RL Int. J. Oral Maxillofac. Surg. 36:858-860(2007). RN [49] RP VARIANT ODDD VAL-2. RX PubMed=18161618; DOI=10.1080/13816810701538620; RA de la Parra D.R., Zenteno J.C.; RT "A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia RT associated to uncommon features."; RL Ophthalmic Genet. 28:198-202(2007). RN [50] RP VARIANTS ODDD VAL-7; VAL-40; PRO-49; GLN-49 INS; ALA-96; PRO-106; ALA-154; RP PHE-201 AND HIS-202. RX PubMed=19338053; DOI=10.1002/humu.20958; RA Paznekas W.A., Karczeski B., Vermeer S., Lowry R.B., Delatycki M., RA Laurence F., Koivisto P.A., Van Maldergem L., Boyadjiev S.A., RA Bodurtha J.N., Jabs E.W.; RT "GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the RT oculodentodigital dysplasia phenotype."; RL Hum. Mutat. 30:724-733(2009). RN [51] RP VARIANTS ODDD PRO-11 AND 41-VAL--ALA-44 DEL. RX PubMed=21670345; DOI=10.1001/archophthalmol.2011.113; RA Gabriel L.A., Sachdeva R., Marcotty A., Rockwood E.J., Traboulsi E.I.; RT "Oculodentodigital dysplasia: new ocular findings and a novel connexin 43 RT mutation."; RL Arch. Ophthalmol. 129:781-784(2011). RN [52] RP VARIANT ODDD ARG-206. RX PubMed=23550541; DOI=10.1111/cge.12158; RA Brice G., Ostergaard P., Jeffery S., Gordon K., Mortimer P.S., Mansour S.; RT "A novel mutation in GJA1 causing oculodentodigital syndrome and primary RT lymphoedema in a three generation family."; RL Clin. Genet. 84:378-381(2013). RN [53] RP VARIANT CMDR GLN-239. RX PubMed=23951358; DOI=10.1371/journal.pone.0073576; RA Hu Y., Chen I.P., de Almeida S., Tiziani V., Do Amaral C.M., RA Gowrishankar K., Passos-Bueno M.R., Reichenberger E.J.; RT "A novel autosomal recessive GJA1 missense mutation linked to RT Craniometaphyseal dysplasia."; RL PLoS ONE 8:E73576-E73576(2013). RN [54] RP VARIANTS ODDD HIS-47; TYR-86 AND ARG-106. RX PubMed=24508941; DOI=10.1016/j.gene.2014.01.066; RA Jamsheer A., Sowinska-Seidler A., Socha M., Stembalska A., Kiraly-Borri C., RA Latos-Bielenska A.; RT "Three novel GJA1 missense substitutions resulting in oculo-dento-digital RT dysplasia (ODDD) - further extension of the mutational spectrum."; RL Gene 539:157-161(2014). RN [55] RP VARIANT ODDD ILE-11. RX PubMed=28258662; DOI=10.1111/odi.12663; RA Porntaveetus T., Srichomthong C., Ohazama A., Suphapeetiporn K., RA Shotelersuk V.; RT "A novel GJA1 mutation in oculodentodigitaldysplasia with extensive loss of RT enamel."; RL Oral Dis. 23:795-800(2017). CC -!- FUNCTION: Structural component of the gap junction, a specialized CC intercellular structure consisting of a cluster of closely packed pairs CC of transmembrane channels, the connexons, that allow passage of small CC molecules and electrical signals between neighboring cells (By CC similarity). Forms homotypic and heterotypic channels gated by CC transjunctional voltage (By similarity). May play a critical role in CC the physiology of hearing by participating in the recycling of CC potassium to the cochlear endolymph (Probable). Negative regulator of CC bladder functional capacity: acts by enhancing intercellular electrical CC and chemical transmission, thus sensitizing bladder muscles to CC cholinergic neural stimuli and causing them to contract (By CC similarity). May play a role in the conductive system of ventricular CC myocardium and heart morphogenesis (By similarity). May play a role in CC cell growth inhibition through the regulation of NOV expression and CC localization (By similarity). Involved in intercellular innate immune CC signaling (PubMed:24077100, PubMed:31992625, PubMed:40010341). Mediates CC translocation of 2',3'-cGAMP and 2',5'-oligoadenylates (2-5A) second CC messengers from virus-infected cells to macrophages and uninfected CC neighboring cells to propagate and amplify the antiviral immune CC response (PubMed:24077100, PubMed:31992625, PubMed:40010341). CC {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P23242, CC ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:31992625, CC ECO:0000269|PubMed:40010341, ECO:0000305|PubMed:11741837}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2',3'-cGAMP(out) = 2',3'-cGAMP(in); Xref=Rhea:RHEA:66320, CC ChEBI:CHEBI:143093; Evidence={ECO:0000269|PubMed:24077100, CC ECO:0000269|PubMed:31992625}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5'-triphosphoadenylyl-(2'->5')-adenylyl-(2'->5')- CC adenosine(out) = 5'-triphosphoadenylyl-(2'->5')-adenylyl-(2'->5')- CC adenosine(in); Xref=Rhea:RHEA:85019, ChEBI:CHEBI:67143; CC Evidence={ECO:0000269|PubMed:40010341}; CC -!- SUBUNIT: A connexon/hemichannel is composed of a hexamer of connexins CC (By similarity). Forms functional homotypic gap junctions consisting of CC identical hemichannels both made of the same connexin type as well as CC heterotypic gap junctions consisting of two different hemichannels, CC each containing a different type of connexin (By similarity). Assembles CC with GJC1 to form heterotypic gap junction channels (By similarity). CC Interacts (via C-terminus) with TJP1 (By similarity). Interacts (via C- CC terminus) with SRC (via SH3 domain) (By similarity). Interacts (not CC ubiquitinated) with UBQLN4 (via UBA domain) (By similarity). Interacts CC with SGSM3 and CNST (By similarity). Interacts with RIC1/CIP150. CC Interacts with CSNK1D. Interacts with NOV (PubMed:15181016, CC PubMed:15213231). Interacts with TMEM65 (By similarity). Interacts with CC ANK3/ANKG and PKP2 (By similarity). {ECO:0000250|UniProtKB:P08050, CC ECO:0000250|UniProtKB:P23242, ECO:0000269|PubMed:12270943, CC ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15213231, CC ECO:0000269|PubMed:16112082}. CC -!- INTERACTION: CC P17302; Q02410: APBA1; NbExp=2; IntAct=EBI-1103439, EBI-368690; CC P17302; Q99767: APBA2; NbExp=2; IntAct=EBI-1103439, EBI-81711; CC P17302; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-1103439, EBI-2875816; CC P17302; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1103439, EBI-747505; CC P17302; O43889-2: CREB3; NbExp=4; IntAct=EBI-1103439, EBI-625022; CC P17302; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-1103439, EBI-9087876; CC P17302; Q12959: DLG1; NbExp=3; IntAct=EBI-1103439, EBI-357481; CC P17302; Q15700: DLG2; NbExp=2; IntAct=EBI-1103439, EBI-80426; CC P17302; Q92796: DLG3; NbExp=3; IntAct=EBI-1103439, EBI-80440; CC P17302; P78352: DLG4; NbExp=3; IntAct=EBI-1103439, EBI-80389; CC P17302; Q02487-1: DSC2; NbExp=2; IntAct=EBI-1103439, EBI-6900677; CC P17302; Q68DX3: FRMPD2; NbExp=3; IntAct=EBI-1103439, EBI-53993476; CC P17302; A4D2P6: GRID2IP; NbExp=2; IntAct=EBI-1103439, EBI-15893226; CC P17302; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-1103439, EBI-5349621; CC P17302; Q9C0E4: GRIP2; NbExp=5; IntAct=EBI-1103439, EBI-949557; CC P17302; Q14005: IL16; NbExp=3; IntAct=EBI-1103439, EBI-2831580; CC P17302; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-1103439, EBI-739832; CC P17302; Q8N448: LNX2; NbExp=2; IntAct=EBI-1103439, EBI-2340947; CC P17302; Q96QZ7: MAGI1; NbExp=2; IntAct=EBI-1103439, EBI-924464; CC P17302; Q86UL8: MAGI2; NbExp=5; IntAct=EBI-1103439, EBI-311035; CC P17302; O75970: MPDZ; NbExp=3; IntAct=EBI-1103439, EBI-821405; CC P17302; Q86UT5: NHERF4; NbExp=2; IntAct=EBI-1103439, EBI-8744528; CC P17302; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-1103439, EBI-10317425; CC P17302; Q8NI35: PATJ; NbExp=8; IntAct=EBI-1103439, EBI-724390; CC P17302; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-1103439, EBI-349819; CC P17302; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-1103439, EBI-10485931; CC P17302; Q14160: SCRIB; NbExp=3; IntAct=EBI-1103439, EBI-357345; CC P17302; Q07157: TJP1; NbExp=5; IntAct=EBI-1103439, EBI-79553; CC P17302; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-1103439, EBI-10694905; CC P17302; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-1103439, EBI-2548832; CC P17302; Q9P202: WHRN; NbExp=3; IntAct=EBI-1103439, EBI-310886; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22411987, CC ECO:0000269|PubMed:25398053}; Multi-pass membrane protein CC {ECO:0000255}. Cell junction, gap junction CC {ECO:0000269|PubMed:22411987, ECO:0000269|PubMed:25225338, CC ECO:0000269|PubMed:25398053, ECO:0000269|PubMed:38375917}. Endoplasmic CC reticulum {ECO:0000250|UniProtKB:P23242}. Cell junction CC {ECO:0000269|PubMed:26604139, ECO:0000269|PubMed:34905516}. CC Note=Localizes at the intercalated disk (ICD) between two adjacent CC cardiomyocytes and the proper localization at ICD is dependent on CC TMEM65. {ECO:0000250|UniProtKB:P23242}. CC -!- TISSUE SPECIFICITY: Expressed at intercalated disks in the heart (at CC protein level) (PubMed:11741837, PubMed:18662195, PubMed:38375917). CC Expressed in the fetal cochlea (PubMed:11741837). Expressed by CC keratinocytes in the skin (at protein level) (PubMed:26604139). CC {ECO:0000269|PubMed:11741837, ECO:0000269|PubMed:18662195, CC ECO:0000269|PubMed:26604139, ECO:0000269|PubMed:34905516, CC ECO:0000269|PubMed:38375917}. CC -!- PTM: Phosphorylated at Ser-368 by PRKCG; phosphorylation induces CC disassembly of gap junction plaques and inhibition of gap junction CC activity (By similarity). Phosphorylation at Ser-325, Ser-328 and Ser- CC 330 by CK1 modulates gap junction assembly. Phosphorylation at Ser-368 CC by PRKCD triggers its internalization into small vesicles leading to CC proteasome-mediated degradation (By similarity). Phosphorylation by CC MAPK1/MAPK3 at Ser-279 and Ser-282 leads to increased ubiquitination CC and lysosomal degradation (By similarity). CC {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P23242, CC ECO:0000250|UniProtKB:Q6TYA7, ECO:0000269|PubMed:12270943, CC ECO:0000269|PubMed:14702389, ECO:0000269|PubMed:15605363}. CC -!- PTM: Ubiquitination results in lysosomal degradation. CC {ECO:0000250|UniProtKB:P23242}. CC -!- PTM: Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the CC level of functional Cx43 gap junctions at the plasma membrane. May be CC desumoylated by SENP1 or SENP2. {ECO:0000269|PubMed:22411987}. CC -!- PTM: S-nitrosylation at Cys-271 is enriched at the muscle endothelial CC gap junction in arteries, it augments channel permeability and may CC regulate of smooth muscle cell to endothelial cell communication. CC {ECO:0000250|UniProtKB:P23242}. CC -!- PTM: Acetylated in the developing cortex; leading to delocalization CC from the cell membrane. {ECO:0000250|UniProtKB:P23242}. CC -!- DISEASE: Oculodentodigital dysplasia (ODDD) [MIM:164200]: A disease CC characterized by a typical facial appearance and variable involvement CC of the eyes, dentition, and fingers. Characteristic facial features CC include a narrow, pinched nose with hypoplastic alae nasi, prominent CC columella and thin anteverted nares together with a narrow nasal CC bridge, and prominent epicanthic folds giving the impression of CC hypertelorism. The teeth are usually small and carious. Typical eye CC findings include microphthalmia and microcornea. The characteristic CC digital malformation is complete syndactyly of the fourth and fifth CC fingers (syndactyly type III) but the third finger may be involved and CC associated camptodactyly is a common finding. Cardiac abnormalities are CC observed in rare instances. {ECO:0000269|PubMed:16816024}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Oculodentodigital dysplasia, autosomal recessive (ODDD-AR) CC [MIM:257850]: A disease characterized by a typical facial appearance CC and variable involvement of the eyes, dentition, and fingers. CC Characteristic facial features include a narrow, pinched nose with CC hypoplastic alae nasi, prominent columella and thin anteverted nares CC together with a narrow nasal bridge, and prominent epicanthic folds CC giving the impression of hypertelorism. The teeth are usually small and CC carious. Typical eye findings include microphthalmia and microcornea. CC The characteristic digital malformation is complete syndactyly of the CC fourth and fifth fingers (syndactyly type III) but the third finger may CC be involved and associated camptodactyly is a common finding. Cardiac CC abnormalities are observed in rare instances. CC {ECO:0000269|PubMed:16816024}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Syndactyly 3 (SDTY3) [MIM:186100]: A form of syndactyly, a CC congenital anomaly of the hand or foot marked by persistence of the CC webbing between adjacent digits that are more or less completely CC attached. In SDTY3, there is usually complete and bilateral syndactyly CC between the fourth and fifth fingers. Usually it is soft tissue CC syndactyly but occasionally the distal phalanges are fused. The fifth CC finger is short with absent or rudimentary middle phalanx. The feet are CC not affected. {ECO:0000269|PubMed:14729836}. Note=The disease may be CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Hypoplastic left heart syndrome 1 (HLHS1) [MIM:241550]: A CC syndrome due to defective development of the aorta proximal to the CC entrance of the ductus arteriosus, and hypoplasia of the left ventricle CC and mitral valve. As a result of the abnormal circulation, the ductus CC arteriosus and foramen ovale are patent and the right atrium, right CC ventricle, and pulmonary artery are enlarged. CC {ECO:0000269|PubMed:11470490}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Hallermann-Streiff syndrome (HSS) [MIM:234100]: A disorder CC characterized by a typical skull shape (brachycephaly with frontal CC bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, CC micrognathia, skin atrophy, dental anomalies and proportionate short CC stature. Intellectual disability is present in a minority of cases. CC {ECO:0000269|PubMed:14974090}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Craniometaphyseal dysplasia, autosomal recessive (CMDR) CC [MIM:218400]: An osteochondrodysplasia characterized by hyperostosis CC and sclerosis of the craniofacial bones associated with abnormal CC modeling of the metaphyses. Sclerosis of the skull may lead to CC asymmetry of the mandible, as well as to cranial nerve compression, CC that may finally result in hearing loss and facial palsy. CC {ECO:0000269|PubMed:23951358}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Erythrokeratodermia variabilis et progressiva 3 (EKVP3) CC [MIM:617525]: A form of erythrokeratodermia variabilis et progressiva, CC a genodermatosis characterized by the coexistence of two independent CC skin lesions: transient erythema and hyperkeratosis that is usually CC localized but occasionally occurs in its generalized form. Clinical CC presentation varies significantly within a family and from one family CC to another. Palmoplantar keratoderma is present in around 50% of cases. CC {ECO:0000269|PubMed:25398053}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Palmoplantar keratoderma and congenital alopecia 1 (PPKCA1) CC [MIM:104100]: A rare autosomal dominant disorder characterized by CC severe hyperkeratosis of the palms and soles, and congenital CC hypotrichosis or alopecia. Dystrophic nail changes occur in some CC patients. {ECO:0000269|PubMed:25168385}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II) CC subfamily. {ECO:0000305}. CC -!- CAUTION: PubMed:7715640 reported a mutation Pro-364 linked to CC congenital heart diseases. PubMed:8873667 later shown that it is an CC artifact. {ECO:0000305}. CC -!- CAUTION: PubMed:11741837 reported 2 mutations (Phe-11 and Ala-24) CC linked to non-syndromic autosomal recessive deafness (DFNBG). These CC mutations have subsequently been shown (PubMed:12457340) to involve the CC pseudogene of connexin-43 located on chromosome 5. CC {ECO:0000305|PubMed:12457340}. 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; X52947; CAA37122.1; -; mRNA. DR EMBL; M65188; AAA52131.1; -; mRNA. DR EMBL; AF151980; AAD37802.2; -; Genomic_DNA. DR EMBL; CR541660; CAG46461.1; -; mRNA. DR EMBL; AK312324; BAG35246.1; -; mRNA. DR EMBL; AL139098; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48178.1; -; Genomic_DNA. DR EMBL; BC026329; AAH26329.1; -; mRNA. DR CCDS; CCDS5123.1; -. DR PIR; A35853; A35853. DR RefSeq; NP_000156.1; NM_000165.5. DR PDB; 2LL2; NMR; -; A=234-259. DR PDB; 7F92; EM; 3.10 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7F93; EM; 3.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7F94; EM; 3.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-257. DR PDB; 7XQ9; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7XQB; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7XQD; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L=1-257. DR PDB; 7XQF; EM; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-257. DR PDB; 7XQG; EM; 3.80 A; A/B/C/D/E/F=1-257. DR PDB; 7XQH; EM; 3.80 A; A/B/C/D/E/F=1-257. DR PDB; 7XQI; EM; 3.70 A; A/B/C/D/E/F=1-257. DR PDB; 7XQJ; EM; 4.00 A; A/B/C/D/E/F=1-257. DR PDB; 7Z1T; EM; 2.26 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7Z22; EM; 2.95 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 7Z23; EM; 3.98 A; A/B/C/D/E/F=1-382. DR PDB; 8QKO; EM; 3.73 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR PDB; 8XBM; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=2-257. DR PDB; 9INZ; EM; 3.34 A; A/B/C/D/E/F=1-257. DR PDB; 9RKX; EM; 14.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-382. DR AlphaFoldDB; P17302; -. DR BMRB; P17302; -. DR EMDB; EMD-14452; -. DR EMDB; EMD-14455; -. DR EMDB; EMD-14456; -. DR EMDB; EMD-18468; -. DR EMDB; EMD-31495; -. DR EMDB; EMD-31496; -. DR EMDB; EMD-31497; -. DR EMDB; EMD-33391; -. DR EMDB; EMD-33392; -. DR EMDB; EMD-33393; -. DR EMDB; EMD-33394; -. DR EMDB; EMD-33395; -. DR EMDB; EMD-33396; -. DR EMDB; EMD-33397; -. DR EMDB; EMD-33398; -. DR EMDB; EMD-33399; -. DR EMDB; EMD-38220; -. DR EMDB; EMD-38221; -. DR EMDB; EMD-38223; -. DR EMDB; EMD-54024; -. DR EMDB; EMD-60713; -. DR EMDB; EMD-60717; -. DR EMDB; EMD-60741; -. DR EMDB; EMD-60743; -. DR SMR; P17302; -. DR BioGRID; 108964; 606. DR FunCoup; P17302; 188. DR IntAct; P17302; 190. DR NDEx; IQUERY-CP-GJA1; 16 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000282561; -. DR BindingDB; P17302; -. DR ChEMBL; CHEMBL4680024; -. DR DrugBank; DB00640; Adenosine. DR DrugBank; DB12452; Caprylic alcohol. DR DrugBank; DB01136; Carvedilol. DR DrugCentral; P17302; -. DR TCDB; 1.A.24.1.16; the gap junction-forming connexin (connexin) family. DR GlyGen; P17302; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P17302; -. DR PhosphoSitePlus; P17302; -. DR SwissPalm; P17302; -. DR BioMuta; GJA1; -. DR DMDM; 117706; -. DR jPOST; P17302; -. DR MassIVE; P17302; -. DR PaxDb; 9606-ENSP00000282561; -. DR PeptideAtlas; P17302; -. DR ProteomicsDB; 53467; -. DR Pumba; P17302; -. DR TopDownProteomics; P17302; -. DR ABCD; P17302; 3 sequenced antibodies. DR Antibodypedia; 4382; 1343 antibodies from 51 providers. DR DNASU; 2697; -. DR Ensembl; ENST00000282561.4; ENSP00000282561.3; ENSG00000152661.10. DR Ensembl; ENST00000647564.1; ENSP00000497565.1; ENSG00000152661.10. DR Ensembl; ENST00000649003.1; ENSP00000497283.1; ENSG00000152661.10. DR Ensembl; ENST00000650427.1; ENSP00000497367.1; ENSG00000152661.10. DR Ensembl; ENST00000898933.1; ENSP00000568992.1; ENSG00000152661.10. DR Ensembl; ENST00000912060.1; ENSP00000582119.1; ENSG00000152661.10. DR Ensembl; ENST00000912061.1; ENSP00000582120.1; ENSG00000152661.10. DR GeneID; 2697; -. DR KEGG; hsa:2697; -. DR MANE-Select; ENST00000282561.4; ENSP00000282561.3; NM_000165.5; NP_000156.1. DR UCSC; uc003pyr.4; human. DR AGR; HGNC:4274; -. DR ClinPGx; PA28685; -. DR CTD; 2697; -. DR DisGeNET; 2697; -. DR GeneCards; GJA1; -. DR HGNC; HGNC:4274; GJA1. DR HPA; ENSG00000152661; Low tissue specificity. DR MalaCards; GJA1; -. DR MIM; 104100; phenotype. DR MIM; 121014; gene. DR MIM; 164200; phenotype. DR MIM; 186100; phenotype. DR MIM; 218400; phenotype. DR MIM; 234100; phenotype. DR MIM; 241550; phenotype. DR MIM; 257850; phenotype. DR MIM; 617525; phenotype. DR OpenTargets; ENSG00000152661; -. DR Orphanet; 1010; Autosomal dominant palmoplantar keratoderma and congenital alopecia. DR Orphanet; 90636; Autosomal recessive non-syndromic genetic deafness. DR Orphanet; 1522; Craniometaphyseal dysplasia. DR Orphanet; 317; Erythrokeratodermia variabilis. DR Orphanet; 2248; Hypoplastic left heart syndrome. DR Orphanet; 2710; Oculodentodigital dysplasia. DR Orphanet; 93404; Syndactyly type 3. DR VEuPathDB; HostDB:ENSG00000152661; -. DR eggNOG; ENOG502QRAE; Eukaryota. DR GeneTree; ENSGT01160000290802; -. DR HOGENOM; CLU_037388_0_0_1; -. DR InParanoid; P17302; -. DR OMA; AFVMIQW; -. DR OrthoDB; 8773830at2759; -. DR PAN-GO; P17302; 5 GO annotations based on evolutionary models. DR PhylomeDB; P17302; -. DR PathwayCommons; P17302; -. DR Reactome; R-HSA-190704; Oligomerization of connexins into connexons. DR Reactome; R-HSA-190827; Transport of connexins along the secretory pathway. DR Reactome; R-HSA-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane. DR Reactome; R-HSA-190861; Gap junction assembly. DR Reactome; R-HSA-190873; Gap junction degradation. DR Reactome; R-HSA-191650; Regulation of gap junction activity. DR Reactome; R-HSA-196025; Formation of annular gap junctions. DR Reactome; R-HSA-9013406; RHOQ GTPase cycle. DR Reactome; R-HSA-9013409; RHOJ GTPase cycle. DR Reactome; R-HSA-9705677; SARS-CoV-2 targets PDZ proteins in cell-cell junction. DR Reactome; R-HSA-9856532; Mechanical load activates signaling by PIEZO1 and integrins in osteocytes. DR SignaLink; P17302; -. DR SIGNOR; P17302; -. DR Agora; ENSG00000152661; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 2697; 29 hits in 1120 CRISPR screens. DR ChiTaRS; GJA1; human. DR GeneWiki; GJA1; -. DR GenomeRNAi; 2697; -. DR Pharos; P17302; Tbio. DR PRO; PR:P17302; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P17302; protein. DR Bgee; ENSG00000152661; Expressed in lateral globus pallidus and 204 other cell types or tissues. DR ExpressionAtlas; P17302; baseline and differential. DR GO; GO:0070161; C:anchoring junction; ISS:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0030054; C:cell junction; IDA:UniProtKB. DR GO; GO:0044291; C:cell-cell contact zone; IDA:ARUK-UCL. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0005922; C:connexin complex; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005921; C:gap junction; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome. DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL. DR GO; GO:0005882; C:intermediate filament; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; ISS:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL. DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB. DR GO; GO:0008013; F:beta-catenin binding; IPI:ARUK-UCL. DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISS:ARUK-UCL. DR GO; GO:0005243; F:gap junction channel activity; IDA:BHF-UCL. DR GO; GO:0086075; F:gap junction channel activity involved in cardiac conduction electrical coupling; NAS:BHF-UCL. DR GO; GO:1903763; F:gap junction channel activity involved in cell communication by electrical coupling; IDA:BHF-UCL. DR GO; GO:0055077; F:gap junction hemi-channel activity; IMP:UniProtKB. DR GO; GO:0034634; F:glutathione transmembrane transporter activity; ISS:ARUK-UCL. DR GO; GO:0015075; F:monoatomic ion transmembrane transporter activity; IDA:BHF-UCL. DR GO; GO:1990782; F:protein tyrosine kinase binding; IEA:Ensembl. DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl. DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB. DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; TAS:BHF-UCL. DR GO; GO:0060348; P:bone development; ISS:UniProtKB. DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB. DR GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL. DR GO; GO:0010644; P:cell communication by electrical coupling; IDA:BHF-UCL. DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; NAS:BHF-UCL. DR GO; GO:0007267; P:cell-cell signaling; IDA:BHF-UCL. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0071467; P:cellular response to pH; IEA:Ensembl. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:ARUK-UCL. DR GO; GO:0140115; P:export across plasma membrane; ISS:ARUK-UCL. DR GO; GO:0016264; P:gap junction assembly; TAS:UniProtKB. DR GO; GO:0014047; P:glutamate secretion; ISS:ARUK-UCL. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0008104; P:intracellular protein localization; IMP:ARUK-UCL. DR GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0099111; P:microtubule-based transport; IMP:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB. DR GO; GO:0032277; P:negative regulation of gonadotropin secretion; IMP:ARUK-UCL. DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IMP:ARUK-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:1905772; P:positive regulation of mesodermal cell differentiation; IMP:ARUK-UCL. DR GO; GO:1905332; P:positive regulation of morphogenesis of an epithelium; IMP:ARUK-UCL. DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:ARUK-UCL. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:ARUK-UCL. DR GO; GO:0007165; P:signal transduction; IDA:BHF-UCL. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl. DR GO; GO:0042908; P:xenobiotic transport; ISS:ARUK-UCL. DR FunFam; 1.20.1440.80:FF:000001; Gap junction alpha-1; 1. DR FunFam; 1.20.5.1130:FF:000001; Gap junction alpha-1; 1. DR Gene3D; 1.20.5.1130; Connexin43; 1. DR Gene3D; 1.20.1440.80; Gap junction channel protein cysteine-rich domain; 1. DR InterPro; IPR035091; Alpha_helix_dom_sf. DR InterPro; IPR000500; Connexin. DR InterPro; IPR002261; Connexin43. DR InterPro; IPR013124; Connexin43_C. DR InterPro; IPR034634; Connexin_C. DR InterPro; IPR019570; Connexin_CCC. DR InterPro; IPR017990; Connexin_CS. DR InterPro; IPR013092; Connexin_N. DR InterPro; IPR038359; Connexin_N_sf. DR PANTHER; PTHR11984; CONNEXIN; 1. DR PANTHER; PTHR11984:SF33; GAP JUNCTION ALPHA-1 PROTEIN; 1. DR Pfam; PF00029; Connexin; 1. DR Pfam; PF03508; Connexin43; 1. DR PRINTS; PR00206; CONNEXIN. DR PRINTS; PR01132; CONNEXINA1. DR SMART; SM00037; CNX; 1. DR SMART; SM01089; Connexin_CCC; 1. DR SUPFAM; SSF118220; Connexin43; 1. DR PROSITE; PS00407; CONNEXINS_1; 1. DR PROSITE; PS00408; CONNEXINS_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cataract; Cell junction; Cell membrane; KW Disease variant; Disulfide bond; Endoplasmic reticulum; Gap junction; KW Hypotrichosis; Immunity; Innate immunity; Isopeptide bond; Membrane; KW Palmoplantar keratoderma; Phosphoprotein; Proteomics identification; KW Reference proteome; S-nitrosylation; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P08050" FT CHAIN 2..382 FT /note="Gap junction alpha-1 protein" FT /id="PRO_0000057801" FT TOPO_DOM 2..23 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P08050" FT TRANSMEM 24..44 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 45..76 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P08050" FT TRANSMEM 77..97 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 98..155 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P08050" FT TRANSMEM 156..176 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 177..207 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P08050" FT TRANSMEM 208..228 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 229..382 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P08050" FT REGION 244..382 FT /note="Interaction with NOV" FT /evidence="ECO:0000250|UniProtKB:P08050" FT REGION 264..382 FT /note="Interaction with UBQLN4" FT /evidence="ECO:0000250|UniProtKB:P23242" FT REGION 317..382 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 317..332 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 362..374 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08050" FT MOD_RES 247 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15605363, FT ECO:0007744|PubMed:21406692" FT MOD_RES 262 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:14702389, FT ECO:0000269|PubMed:15605363" FT MOD_RES 271 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 275 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 279 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 282 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 306 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 325 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:12270943" FT MOD_RES 326 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 328 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:12270943" FT MOD_RES 330 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:12270943" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 368 FT /note="Phosphoserine; by PKC/PRKCG and PKC/PRKCD" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 373 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08050" FT DISULFID 54..192 FT /evidence="ECO:0000269|PubMed:9430691" FT DISULFID 187..198 FT /evidence="ECO:0000269|PubMed:9430691" FT CROSSLNK 144 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:22411987" FT CROSSLNK 237 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:22411987" FT VARIANT 2 FT /note="G -> V (in ODDD)" FT /evidence="ECO:0000269|PubMed:18161618" FT /id="VAR_058990" FT VARIANT 7 FT /note="L -> V (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_058991" FT VARIANT 8 FT /note="G -> V (in PPKCA1; can form functional gap FT junctions; results in enhanced hemichannel activity that FT causes increased cell death; dbSNP:rs864309644)" FT /evidence="ECO:0000269|PubMed:25168385" FT /id="VAR_075754" FT VARIANT 11 FT /note="L -> I (in ODDD)" FT /evidence="ECO:0000269|PubMed:28258662" FT /id="VAR_078238" FT VARIANT 11 FT /note="L -> P (in ODDD; dbSNP:rs121912969)" FT /evidence="ECO:0000269|PubMed:16709485, FT ECO:0000269|PubMed:21670345" FT /id="VAR_058992" FT VARIANT 17 FT /note="Y -> S (in ODDD; dbSNP:rs104893961)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015747" FT VARIANT 18 FT /note="S -> P (in ODDD; dbSNP:rs104893962)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015748" FT VARIANT 21 FT /note="G -> R (in ODDD; dbSNP:rs104893963)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015749" FT VARIANT 22 FT /note="G -> E (in ODDD; dbSNP:rs104893964)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015750" FT VARIANT 23 FT /note="K -> T (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015751" FT VARIANT 27 FT /note="S -> P (in ODDD)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_038356" FT VARIANT 31 FT /note="I -> M (in ODDD)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_038357" FT VARIANT 40 FT /note="A -> V (in ODDD; dbSNP:rs1554200992)" FT /evidence="ECO:0000269|PubMed:12457340, FT ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:16378922, FT ECO:0000269|PubMed:19338053" FT /id="VAR_015752" FT VARIANT 41..44 FT /note="Missing (in ODDD)" FT /evidence="ECO:0000269|PubMed:21670345" FT /id="VAR_070439" FT VARIANT 41 FT /note="V -> L (found in a patient with hidrotic ectodermal FT dysplasia, abortive features of oculodentodigital dysplasia FT and extensive hyperkeratosis of the skin; uncertain FT significance; the patient also carries GJB2 variant H-127)" FT /evidence="ECO:0000269|PubMed:15757815" FT /id="VAR_058993" FT VARIANT 44 FT /note="A -> V (in EKVP3; loss of localization to the plasma FT membrane, retention in the Golgi apparatus; FT dbSNP:rs794729675)" FT /evidence="ECO:0000269|PubMed:25398053" FT /id="VAR_075755" FT VARIANT 47 FT /note="D -> H (in ODDD)" FT /evidence="ECO:0000269|PubMed:24508941" FT /id="VAR_071009" FT VARIANT 49 FT /note="Q -> K (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015753" FT VARIANT 49 FT /note="Q -> P (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_058994" FT VARIANT 49 FT /note="Q -> QQ (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_058995" FT VARIANT 52 FT /note="F -> FF (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015754" FT VARIANT 59 FT /note="P -> H (in ODDD)" FT /evidence="ECO:0000269|PubMed:16219735" FT /id="VAR_058996" FT VARIANT 69 FT /note="S -> Y (in ODDD)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_038358" FT VARIANT 76 FT /note="R -> H (in HSS; overlapping features with FT oculodentodigital dysplasia; dbSNP:rs267606844)" FT /evidence="ECO:0000269|PubMed:14974090" FT /id="VAR_058997" FT VARIANT 76 FT /note="R -> S (in ODDD; dbSNP:rs267606845)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015755" FT VARIANT 86 FT /note="S -> Y (in ODDD; de novo mutation found in a FT sporadic case)" FT /evidence="ECO:0000269|PubMed:24508941" FT /id="VAR_071010" FT VARIANT 90 FT /note="L -> V (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015756" FT VARIANT 95 FT /note="H -> R (in ODDD)" FT /evidence="ECO:0000269|PubMed:16222672" FT /id="VAR_058998" FT VARIANT 96 FT /note="V -> A (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_058999" FT VARIANT 96 FT /note="V -> E (in ODDD)" FT /evidence="ECO:0000269|PubMed:16813608" FT /id="VAR_059000" FT VARIANT 96 FT /note="V -> M (in ODDD; dbSNP:rs28931601)" FT /evidence="ECO:0000269|PubMed:15108203" FT /id="VAR_059001" FT VARIANT 98 FT /note="Y -> C (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015757" FT VARIANT 102 FT /note="K -> N (in ODDD; dbSNP:rs1554201011)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015758" FT VARIANT 106 FT /note="L -> P (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_059002" FT VARIANT 106 FT /note="L -> R (in ODDD)" FT /evidence="ECO:0000269|PubMed:24508941" FT /id="VAR_071011" FT VARIANT 110 FT /note="E -> D (in ODDD)" FT /evidence="ECO:0000269|PubMed:16378922" FT /id="VAR_059003" FT VARIANT 113 FT /note="L -> P (in ODDD)" FT /evidence="ECO:0000269|PubMed:14729836, FT ECO:0000269|PubMed:16813608" FT /id="VAR_038359" FT VARIANT 130 FT /note="I -> T (in ODDD; dbSNP:rs1554201017)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015759" FT VARIANT 134 FT /note="K -> E (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015760" FT VARIANT 134 FT /note="K -> N (in ODDD)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_038360" FT VARIANT 138 FT /note="G -> R (in ODDD)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015761" FT VARIANT 143 FT /note="G -> S (in SDTY3; dbSNP:rs28931600)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_038361" FT VARIANT 147 FT /note="M -> T (in ODDD; dbSNP:rs1057518872)" FT /evidence="ECO:0000269|PubMed:16378922" FT /id="VAR_059004" FT VARIANT 148 FT /note="R -> Q (in ODDD; dbSNP:rs962041031)" FT /evidence="ECO:0000269|PubMed:14729836" FT /id="VAR_014095" FT VARIANT 154 FT /note="T -> A (in ODDD)" FT /evidence="ECO:0000269|PubMed:17509830, FT ECO:0000269|PubMed:19338053" FT /id="VAR_059005" FT VARIANT 154 FT /note="T -> N (in ODDD)" FT /evidence="ECO:0000269|PubMed:16813608" FT /id="VAR_059006" FT VARIANT 168 FT /note="A -> T (in dbSNP:rs2228961)" FT /id="VAR_014096" FT VARIANT 169 FT /note="Missing (in ODDD)" FT /evidence="ECO:0000269|PubMed:16378922" FT /id="VAR_059007" FT VARIANT 194 FT /note="H -> P (in ODDD; atypical form of ODDD characterized FT by the predominance of the ocular involvement and by the FT absence of hand and/or foot syndactyly and absence of any FT neurologic signs; dbSNP:rs104893966)" FT /evidence="ECO:0000269|PubMed:15637728" FT /id="VAR_059008" FT VARIANT 201 FT /note="S -> F (in ODDD)" FT /evidence="ECO:0000269|PubMed:19338053" FT /id="VAR_059009" FT VARIANT 202 FT /note="R -> H (in ODDD; dbSNP:rs750294638)" FT /evidence="ECO:0000269|PubMed:12457340, FT ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:19338053" FT /id="VAR_015762" FT VARIANT 206 FT /note="K -> R (in ODDD; dbSNP:rs397518464)" FT /evidence="ECO:0000269|PubMed:23550541" FT /id="VAR_070440" FT VARIANT 216 FT /note="V -> L (in ODDD; dbSNP:rs1554201043)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015763" FT VARIANT 220 FT /note="S -> Y (in ODDD)" FT /evidence="ECO:0000269|PubMed:16813608" FT /id="VAR_059010" FT VARIANT 227 FT /note="E -> D (in EKVP3; loss of localization to the plasma FT membrane, retention in the Golgi apparatus; FT dbSNP:rs875989815)" FT /evidence="ECO:0000269|PubMed:25398053" FT /id="VAR_075756" FT VARIANT 239 FT /note="R -> Q (in CMDR; dbSNP:rs764670582)" FT /evidence="ECO:0000269|PubMed:23951358" FT /id="VAR_070441" FT VARIANT 239 FT /note="R -> W (in congenital heart malformations)" FT /evidence="ECO:0000269|PubMed:15978203" FT /id="VAR_014100" FT VARIANT 251 FT /note="S -> T (in congenital heart malformations)" FT /evidence="ECO:0000269|PubMed:15978203" FT /id="VAR_059011" FT VARIANT 253 FT /note="A -> P (in congenital heart malformations)" FT /evidence="ECO:0000269|PubMed:15978203" FT /id="VAR_059012" FT VARIANT 253 FT /note="A -> V (in dbSNP:rs17653265)" FT /evidence="ECO:0000269|PubMed:12457340" FT /id="VAR_015764" FT VARIANT 283 FT /note="P -> L (in congenital heart malformations)" FT /evidence="ECO:0000269|PubMed:15978203" FT /id="VAR_014101" FT VARIANT 290 FT /note="T -> N (in congenital heart malformations)" FT /evidence="ECO:0000269|PubMed:15978203" FT /id="VAR_014102" FT VARIANT 326 FT /note="T -> A" FT /evidence="ECO:0000269|PubMed:7715640" FT /id="VAR_059013" FT VARIANT 352 FT /note="E -> G (in heart malformations)" FT /evidence="ECO:0000269|PubMed:7715640" FT /id="VAR_059014" FT VARIANT 362 FT /note="R -> Q (in HLHS1; uncertain significance; abolishes FT phosphorylation by PKA and PKC when associated with Q-376; FT dbSNP:rs2227885)" FT /evidence="ECO:0000269|PubMed:11470490" FT /id="VAR_032924" FT VARIANT 364 FT /note="S -> P (in heart malformations; shows abnormalities FT in the regulation of cell-cell communication as compared FT with cells expressing normal GJA1)" FT /evidence="ECO:0000269|PubMed:7715640" FT /id="VAR_059015" FT VARIANT 365 FT /note="S -> N (in heart malformations)" FT /evidence="ECO:0000269|PubMed:7715640" FT /id="VAR_059016" FT VARIANT 373 FT /note="S -> G" FT /evidence="ECO:0000269|PubMed:7715640" FT /id="VAR_059017" FT VARIANT 376 FT /note="R -> Q (in HLHS1; uncertain significance; abolishes FT phosphorylation by PKA and PKC when associated with Q-362; FT dbSNP:rs104893965)" FT /evidence="ECO:0000269|PubMed:11470490" FT /id="VAR_032925" FT HELIX 4..15 FT /evidence="ECO:0007829|PDB:7Z1T" FT STRAND 16..18 FT /evidence="ECO:0007829|PDB:7F92" FT HELIX 22..35 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 36..41 FT /evidence="ECO:0007829|PDB:7Z1T" FT TURN 45..50 FT /evidence="ECO:0007829|PDB:7Z1T" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 61..69 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 74..104 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 126..136 FT /evidence="ECO:0007829|PDB:8XBM" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:8XBM" FT HELIX 152..176 FT /evidence="ECO:0007829|PDB:7Z1T" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:7Z1T" FT STRAND 190..194 FT /evidence="ECO:0007829|PDB:7Z1T" FT STRAND 196..199 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 203..234 FT /evidence="ECO:0007829|PDB:7Z1T" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:2LL2" FT HELIX 246..253 FT /evidence="ECO:0007829|PDB:2LL2" FT HELIX 255..257 FT /evidence="ECO:0007829|PDB:2LL2" SQ SEQUENCE 382 AA; 43008 MW; 7DDDAD8040284176 CRC64; MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG VNVDMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSIFEVAFL LIQWYIYGFS LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGKSDPYHAT SGALSPAKDC GSQKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI //