CXB2_HUMAN
ID CXB2_HUMAN Reviewed; 226 AA.
AC P29033; Q508A5; Q508A6; Q5YLL0; Q5YLL1; Q5YLL4; Q6IPV5; Q86U88; Q96AK0;
AC Q9H536; Q9NNY4;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 3.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Gap junction beta-2 protein;
DE AltName: Full=Connexin-26 {ECO:0000303|PubMed:11439000, ECO:0000303|PubMed:21094651};
DE Short=Cx26 {ECO:0000303|PubMed:21094651};
GN Name=GJB2;
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].
RX PubMed=1324944; DOI=10.1083/jcb.118.5.1213;
RA Lee S.W., Tomasetto C., Paul D., Keyomarsi K., Sager R.;
RT "Transcriptional downregulation of gap-junction proteins blocks junctional
RT communication in human mammary tumor cell lines.";
RL J. Cell Biol. 118:1213-1221(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1A PRO-79; TRP-143;
RP ALA-178; LYS-203 AND PRO-214, AND VARIANTS DFNA3A GLN-184 AND SER-197.
RC TISSUE=Blood;
RX PubMed=11439000; DOI=10.1002/humu.1156;
RA Hamelmann C., Amedofu G.K., Albrecht K., Muntau B., Gelhaus A.,
RA Brobby G.W., Horstmann R.D.;
RT "Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing
RT impairment in Ghana.";
RL Hum. Mutat. 18:84-85(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT DFNB1A ILE-37, AND VARIANTS
RP 46-ASP--GLN-48 DELINS GLU; HIS-127; ILE-153; SER-160 AND MET-167.
RX PubMed=14722929; DOI=10.1002/humu.9216;
RA Gasmelseed N.M.A., Schmidt M., Magzoub M.M.A., Macharia M., Elmustafa O.M.,
RA Ototo B., Winkler E., Ruge G., Horstmann R.D., Meyer C.G.;
RT "Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and
RT novel GJB2 variants.";
RL Hum. Mutat. 23:206-207(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1A HIS-32; LYS-80; ILE-93;
RP GLU-120 DEL; LYS-129; TRP-143 AND PRO-184, AND VARIANTS ILE-27; GLY-114;
RP HIS-127 AND ILE-153.
RX PubMed=15666300; DOI=10.1002/ajmg.a.30576;
RA Najmabadi H., Nishimura C., Kahrizi K., Riazalhosseini Y., Malekpour M.,
RA Daneshi A., Farhadi M., Mohseni M., Mahdieh N., Ebrahimi A.,
RA Bazazzadegan N., Naghavi A., Avenarius M., Arzhangi S., Smith R.J.H.;
RT "GJB2 mutations: passage through Iran.";
RL Am. J. Med. Genet. A 133:132-137(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Joseph A.Y., Rasool T.J.;
RT "A polymorphism in the genomic sequence of the coding region of connexin 26
RT in the South Indian population.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-32.
RA Joseph A.Y., Rasool T.J.;
RT "A novel mutation in the connexin 26 gene in the South Indian population.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-27 AND GLY-114.
RC TISSUE=Colon;
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 [10]
RP INVOLVEMENT IN DFNB1A.
RX PubMed=15994881; DOI=10.1136/jmg.2004.028324;
RA del Castillo F.J., Rodriguez-Ballesteros M., Alvarez A., Hutchin T.,
RA Leonardi E., de Oliveira C.A., Azaiez H., Brownstein Z., Avenarius M.R.,
RA Marlin S., Pandya A., Shahin H., Siemering K.R., Weil D., Wuyts W.,
RA Aguirre L.A., Martin Y., Moreno-Pelayo M.A., Villamar M., Avraham K.B.,
RA Dahl H.H., Kanaan M., Nance W.E., Petit C., Smith R.J., Van Camp G.,
RA Sartorato E.L., Murgia A., Moreno F., del Castillo I.;
RT "A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found
RT in trans with mutations in the GJB2 gene (connexin-26) in subjects with
RT DFNB1 non-syndromic hearing impairment.";
RL J. Med. Genet. 42:588-594(2005).
RN [11]
RP INTERACTION WITH CNST.
RX PubMed=19864490; DOI=10.1093/hmg/ddp490;
RA del Castillo F.J., Cohen-Salmon M., Charollais A., Caille D., Lampe P.D.,
RA Chavrier P., Meda P., Petit C.;
RT "Consortin, a trans-Golgi network cargo receptor for the plasma membrane
RT targeting and recycling of connexins.";
RL Hum. Mol. Genet. 19:262-275(2010).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY OF MUTANT ALA-34, FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, AND TOPOLOGY.
RX PubMed=17551008; DOI=10.1073/pnas.0703704104;
RA Oshima A., Tani K., Hiroaki Y., Fujiyoshi Y., Sosinsky G.E.;
RT "Three-dimensional structure of a human connexin26 gap junction channel
RT reveals a plug in the vestibule.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10034-10039(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, TOPOLOGY, AND DISULFIDE BONDS.
RX PubMed=19340074; DOI=10.1038/nature07869;
RA Maeda S., Nakagawa S., Suga M., Yamashita E., Oshima A., Fujiyoshi Y.,
RA Tsukihara T.;
RT "Structure of the connexin 26 gap junction channel at 3.5 A resolution.";
RL Nature 458:597-602(2009).
RN [14] {ECO:0007744|PDB:3IZ1, ECO:0007744|PDB:3IZ2}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.00 ANGSTROMS) OF MUTANT ALA-34,
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF 2-ASP--GLN-7;
RP 2-ASP--LEU-10 AND MET-34.
RX PubMed=21094651; DOI=10.1016/j.jmb.2010.10.032;
RA Oshima A., Tani K., Toloue M.M., Hiroaki Y., Smock A., Inukai S., Cone A.,
RA Nicholson B.J., Sosinsky G.E., Fujiyoshi Y.;
RT "Asymmetric configurations and N-terminal rearrangements in connexin26 gap
RT junction channels.";
RL J. Mol. Biol. 405:724-735(2011).
RN [15] {ECO:0007744|PDB:5ER7, ECO:0007744|PDB:5ERA}
RP X-RAY CRYSTALLOGRAPHY (3.29 ANGSTROMS) IN COMPLEX WITH CALCIUM, FUNCTION,
RP SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, AND DISULFIDE BONDS.
RX PubMed=26753910; DOI=10.1038/ncomms9770;
RA Bennett B.C., Purdy M.D., Baker K.A., Acharya C., McIntire W.E.,
RA Stevens R.C., Zhang Q., Harris A.L., Abagyan R., Yeager M.;
RT "An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction
RT channels.";
RL Nat. Commun. 7:8770-8770(2016).
RN [16]
RP VARIANT DFNB1A THR-34.
RX PubMed=9139825; DOI=10.1038/387080a0;
RA Kelsell D.P., Dunlop J., Stevens H.P., Lench N.J., Liang J.N., Parry G.,
RA Mueller R.F., Leigh I.M.;
RT "Connexin 26 mutations in hereditary non-syndromic sensorineural
RT deafness.";
RL Nature 387:80-83(1997).
RN [17]
RP VARIANT DFNB1A THR-34.
RX PubMed=9422505; DOI=10.1038/34079;
RA Scott D.A., Kraft M.L., Tone M.M., Sheffield V.C., Smith R.J.H.;
RT "Connexin mutations and hearing loss.";
RL Nature 391:32-32(1998).
RN [18]
RP VARIANT DFNB1A ARG-77.
RX PubMed=9328482; DOI=10.1093/hmg/6.12.2163;
RA Carrasquillo M.M., Zlotogora J., Barges S., Chakravarti A.;
RT "Two different connexin 26 mutations in an inbred kindred segregating non-
RT syndromic recessive deafness: implications for genetic studies in isolated
RT populations.";
RL Hum. Mol. Genet. 6:2163-2172(1997).
RN [19]
RP VARIANTS DFNB1A GLU-118 DEL AND PRO-184.
RX PubMed=9336442; DOI=10.1093/hmg/6.12.2173;
RA Denoyelle F., Weil D., Maw M.A., Wilcox S.A., Lench N.J.,
RA Allen-Powell D.R., Osborn A.H., Dahl H.-H.M., Middleton A., Houseman M.J.,
RA Dode C., Marlin S., Boulila-ElGaied A., Grati M., Ayadi H., BenArab S.,
RA Bitoun P., Lina-Granade G., Godet J., Mustapha M., Loiselet J., El-Zir E.,
RA Aubois A., Joannard A., Levilliers J., Garabedian E.-N., Mueller R.F.,
RA McKinlay Gardner R.J., Petit C.;
RT "Prelingual deafness: high prevalence of a 30delG mutation in the connexin
RT 26 gene.";
RL Hum. Mol. Genet. 6:2173-2177(1997).
RN [20]
RP VARIANTS DFNB1A LEU-84; MET-95 AND ARG-113, AND VARIANTS ILE-27 AND ILE-37.
RX PubMed=9529365; DOI=10.1086/301807;
RA Kelley P.M., Harris D.J., Comer B.C., Askew J.W., Fowler T., Smith S.D.,
RA Kimberling W.J.;
RT "Novel mutations in the connexin 26 gene (GJB2) that cause autosomal
RT recessive (DFNB1) hearing loss.";
RL Am. J. Hum. Genet. 62:792-799(1998).
RN [21]
RP VARIANT PPKDFN TRP-75.
RX PubMed=9856479; DOI=10.1007/s004390050839;
RA Richard G., White T.W., Smith L.E., Bailey R.A., Compton J.G., Paul D.L.,
RA Bale S.J.;
RT "Functional defects of Cx26 resulting from a heterozygous missense mutation
RT in a family with dominant deaf-mutism and palmoplantar keratoderma.";
RL Hum. Genet. 103:393-399(1998).
RN [22]
RP VARIANTS LEU-83 AND SER-160, AND VARIANT DFNB1A THR-34.
RX PubMed=9600457;
RX DOI=10.1002/(sici)1098-1004(1998)11:5<387::aid-humu6>3.0.co;2-8;
RA Scott D.A., Kraft M.L., Carmi R., Ramesh A., Elbedour K., Yairi Y.,
RA Srikumari Srisailapathy C.R., Rosengren S.S., Markham A.F., Mueller R.F.,
RA Lench N.J., van Camp G., Smith R.J.H., Sheffield V.C.;
RT "Identification of mutations in the connexin 26 gene that cause autosomal
RT recessive nonsyndromic hearing loss.";
RL Hum. Mutat. 11:387-394(1998).
RN [23]
RP VARIANT DFNA3A CYS-44.
RX PubMed=9620796; DOI=10.1038/30639;
RA Denoyelle F., Lina-Granade G., Plauchu H., Bruzzone R., Chaib H.,
RA Levi-Acobas F., Weil D., Petit C.;
RT "Connexin 26 gene linked to a dominant deafness.";
RL Nature 393:319-320(1998).
RN [24]
RP VARIANT DFNB1A TRP-143.
RX PubMed=9471561; DOI=10.1056/nejm199802193380813;
RA Brobby G.W., Muller-Myhsok B., Horstmann R.D.;
RT "Connexin 26 R143W mutation associated with recessive nonsyndromic
RT sensorineural deafness in Africa.";
RL N. Engl. J. Med. 338:548-550(1998).
RN [25]
RP VARIANT VOWNKL HIS-66.
RX PubMed=10369869; DOI=10.1093/hmg/8.7.1237;
RA Maestrini E., Korge B.P., Ocana-Sierra J., Calzolari E., Cambiaghi S.,
RA Scudder P.M., Hovnanian A., Monaco A.P., Munro C.S.;
RT "A missense mutation in connexin26, D66H, causes mutilating keratoderma
RT with sensorineural deafness (Vohwinkel's syndrome) in three unrelated
RT families.";
RL Hum. Mol. Genet. 8:1237-1243(1999).
RN [26]
RP VARIANTS ILE-27; ILE-37; GLY-114 AND THR-203.
RX PubMed=10607953;
RX DOI=10.1002/(sici)1096-8628(20000117)90:2<141::aid-ajmg10>3.0.co;2-g;
RA Kudo T., Ikeda K., Kure S., Matsubara Y., Oshima T., Watanabe K.,
RA Kawase T., Narisawa K., Takasaka T.;
RT "Novel mutations in the connexin 26 gene (GJB2) responsible for childhood
RT deafness in the Japanese population.";
RL Am. J. Med. Genet. 90:141-145(2000).
RN [27]
RP VARIANT PPKDFN HIS-66.
RX PubMed=10757647; DOI=10.1038/sj.ejhg.5200407;
RA Kelsell D.P., Wilgoss A.L., Richard G., Stevens H.P., Munro C.S.,
RA Leigh I.M.;
RT "Connexin mutations associated with palmoplantar keratoderma and profound
RT deafness in a single family.";
RL Eur. J. Hum. Genet. 8:141-144(2000).
RN [28]
RP VARIANTS DFNB1A ILE-37; PRO-90 AND TRP-184.
RX PubMed=10830906; DOI=10.1007/s004390000273;
RA Wilcox S.A., Saunders K., Osborn A.H., Arnold A., Wunderlich J., Kelly T.,
RA Collins V., Wilcox L.J., McKinlay Gardner R.J., Kamarinos M.,
RA Cone-Wesson B., Williamson R., Dahl H.-H.M.;
RT "High frequency hearing loss correlated with mutations in the GJB2 gene.";
RL Hum. Genet. 106:399-405(2000).
RN [29]
RP VARIANT PPKDFN ALA-59.
RX PubMed=10633135; DOI=10.1136/jmg.37.1.50;
RA Heathcote K., Syrris P., Carter N.D., Patton M.A.;
RT "A connexin 26 mutation causes a syndrome of sensorineural hearing loss and
RT palmoplantar hyperkeratosis (MIM 148350).";
RL J. Med. Genet. 37:50-51(2000).
RN [30]
RP VARIANT DFNA3A PHE-202.
RX PubMed=10807696; DOI=10.1136/jmg.37.5.368;
RA Morle L., Bozon M., Alloisio N., Latour P., Vandenberghe A., Plauchu H.,
RA Collet L., Edery P., Godet J., Lina-Granade G.;
RT "A novel C202F mutation in the connexin26 gene (GJB2) associated with
RT autosomal dominant isolated hearing loss.";
RL J. Med. Genet. 37:368-370(2000).
RN [31]
RP VARIANT DFNB1A PRO-90, AND VARIANT DFNA3A GLN-143.
RX PubMed=11313763; DOI=10.1038/sj.ejhg.5200607;
RA Loffler J., Nekahm D., Hirst-Stadlmann A., Gunther B., Menzel H.J.,
RA Utermann G., Janecke A.R.;
RT "Sensorineural hearing loss and the incidence of Cx26 mutations in
RT Austria.";
RL Eur. J. Hum. Genet. 9:226-230(2001).
RN [32]
RP VARIANTS KIDAD ARG-12; PHE-17 AND ASN-50.
RX PubMed=11912510; DOI=10.1086/339986;
RA Richard G., Rouan F., Willoughby C.E., Brown N., Chung P., Ryynanen M.,
RA Jabs E.W., Bale S.J., DiGiovanna J.J., Uitto J., Russell L.;
RT "Missense mutations in GJB2 encoding connexin-26 cause the ectodermal
RT dysplasia keratitis-ichthyosis-deafness syndrome.";
RL Am. J. Hum. Genet. 70:1341-1348(2002).
RN [33]
RP VARIANT DFNB1A VAL-159.
RX PubMed=12239718; DOI=10.1002/ajmg.10621;
RA Gualandi F., Ravani A., Berto A., Sensi A., Trabanelli C., Falciano F.,
RA Trevisi P., Mazzoli M., Tibiletti M.G., Cristofari E., Burdo S.,
RA Ferlini A., Martini A., Calzolari E.;
RT "Exploring the clinical and epidemiological complexity of GJB2-linked
RT deafness.";
RL Am. J. Med. Genet. 112:38-45(2002).
RN [34]
RP VARIANT HID SYNDROME ASN-50.
RX PubMed=12072059; DOI=10.1046/j.1365-2133.2002.04893.x;
RA van Geel M., van Steensel M.A.M., Kuester W., Hennies H.C., Happle R.,
RA Steijlen P.M., Koenig A.;
RT "HID and KID syndromes are associated with the same connexin 26 mutation.";
RL Br. J. Dermatol. 146:938-942(2002).
RN [35]
RP VARIANT DFNB1A ILE-37.
RX PubMed=12121355; DOI=10.1034/j.1399-0004.2002.610611.x;
RA Bason L., Dudley T., Lewis K., Shah U., Potsic W., Ferraris A., Fortina P.,
RA Rappaport E., Krantz I.D.;
RT "Homozygosity for the V37I Connexin 26 mutation in three unrelated children
RT with sensorineural hearing loss.";
RL Clin. Genet. 61:459-464(2002).
RN [36]
RP VARIANT PPKDFN GLN-75.
RX PubMed=12372058; DOI=10.1034/j.1399-0004.2002.620409.x;
RA Uyguner O., Tukel T., Baykal C., Eris H., Emiroglu M., Hafiz G.,
RA Ghanbari A., Baserer N., Yuksel-Apak M., Wollnik B.;
RT "The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing
RT loss and palmoplantar keratoderma in a Turkish family.";
RL Clin. Genet. 62:306-309(2002).
RN [37]
RP VARIANT KIDAD ASN-50.
RX PubMed=12548749; DOI=10.1002/ajmg.a.10851;
RA Alvarez A., Del Castillo I., Pera A., Villamar M., Moreno-Pelayo M.A.,
RA Moreno F., Moreno R., Tapia M.C.;
RT "De novo mutation in the gene encoding connexin-26 (GJB2) in a sporadic
RT case of keratitis-ichthyosis-deafness (KID) syndrome.";
RL Am. J. Med. Genet. A 117:89-91(2003).
RN [38]
RP VARIANTS KIDAD ASN-50 AND TYR-50.
RX PubMed=12752120; DOI=10.1046/j.1365-2133.2003.05245.x;
RA Yotsumoto S., Hashiguchi T., Chen X., Ohtake N., Tomitaka A., Akamatsu H.,
RA Matsunaga K., Shiraishi S., Miura H., Adachi J., Kanzaki T.;
RT "Novel mutations in GJB2 encoding connexin-26 in Japanese patients with
RT keratitis-ichthyosis-deafness syndrome.";
RL Br. J. Dermatol. 148:649-653(2003).
RN [39]
RP VARIANT DFNA3A ASN-179, AND VARIANT DFNB1A ILE-37.
RX PubMed=12786758; DOI=10.1034/j.1399-0004.2003.00079.x;
RA Primignani P., Castorina P., Sironi F., Curcio C., Ambrosetti U.,
RA Coviello D.A.;
RT "A novel dominant missense mutation -- D179N -- in the GJB2 gene (connexin
RT 26) associated with non-syndromic hearing loss.";
RL Clin. Genet. 63:516-521(2003).
RN [40]
RP VARIANTS DEAFNESS GLU-45; THR-71; ARG-86 AND TRP-143, AND VARIANTS ILE-27;
RP ILE-37; GLY-114; ASN-123; LEU-191 AND THR-203.
RX PubMed=12560944; DOI=10.1007/s00439-002-0889-x;
RA Ohtsuka A., Yuge I., Kimura S., Namba A., Abe S., Van Laer L., Van Camp G.,
RA Usami S.;
RT "GJB2 deafness gene shows a specific spectrum of mutations in Japan,
RT including a frequent founder mutation.";
RL Hum. Genet. 112:329-333(2003).
RN [41]
RP CHARACTERIZATION OF VARIANTS DFNA3A SER-44 AND TRP-75, CHARACTERIZATION OF
RP VARIANT PPKDFN ALA-59, AND CHARACTERIZATION OF VARIANT VOWNKL HIS-66.
RX PubMed=12668604; DOI=10.1093/hmg/ddg076;
RA Marziano N.K., Casalotti S.O., Portelli A.E., Becker D.L., Forge A.;
RT "Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have
RT a dominant negative effect on connexin 30.";
RL Hum. Mol. Genet. 12:805-812(2003).
RN [42]
RP VARIANTS ILE-27; THR-111; GLY-114; HIS-127; ILE-153 AND TRP-165.
RX PubMed=12746422; DOI=10.1136/jmg.40.5.e68;
RA Ramshankar M., Girirajan S., Dagan O., Ravi Shankar H.M., Jalvi R.,
RA Rangasayee R., Avraham K.B., Anand A.;
RT "Contribution of connexin26 (GJB2) mutations and founder effect to non-
RT syndromic hearing loss in India.";
RL J. Med. Genet. 40:E68-E68(2003).
RN [43]
RP VARIANT DFNB1A THR-34.
RX PubMed=14694360; DOI=10.1038/sj.ejhg.5201147;
RA Feldmann D., Denoyelle F., Loundon N., Weil D., Garabedian E.N.,
RA Couderc R., Joannard A., Schmerber S., Delobel B., Leman J., Journel H.,
RA Catros H., Ferrec C., Drouin-Garraud V., Obstoy M.F., Moati L., Petit C.,
RA Marlin S.;
RT "Clinical evidence of the nonpathogenic nature of the M34T variant in the
RT connexin 26 gene.";
RL Eur. J. Hum. Genet. 12:279-284(2004).
RN [44]
RP VARIANT BAPS LYS-54.
RX PubMed=15482471; DOI=10.1111/j.0022-202x.2004.23470.x;
RA Richard G., Brown N., Ishida-Yamamoto A., Krol A.;
RT "Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey
RT syndrome is caused by a novel missense mutation in GJB2.";
RL J. Invest. Dermatol. 123:856-863(2004).
RN [45]
RP VARIANT BAPS SER-59.
RX PubMed=15952212; DOI=10.1002/ajmg.a.30822;
RA Alexandrino F., Sartorato E.L., Marques-de-Faria A.P., Steiner C.E.;
RT "G59S mutation in the GJB2 (connexin 26) gene in a patient with Bart-
RT Pumphrey syndrome.";
RL Am. J. Med. Genet. A 136:282-284(2005).
RN [46]
RP VARIANT PPKDFN GLN-75, AND CHARACTERIZATION OF VARIANT PPKDFN GLN-75.
RX PubMed=15996214; DOI=10.1111/j.1399-0004.2005.00468.x;
RA Piazza V., Beltramello M., Menniti M., Colao E., Malatesta P., Argento R.,
RA Chiarella G., Gallo L.V., Catalano M., Perrotti N., Mammano F.,
RA Cassandro E.;
RT "Functional analysis of R75Q mutation in the gene coding for Connexin 26
RT identified in a family with nonsyndromic hearing loss.";
RL Clin. Genet. 68:161-166(2005).
RN [47]
RP VARIANT VOWNKL VAL-130, AND VARIANTS HIS-117; PHE-142 DEL AND PRO-148.
RX PubMed=15954104; DOI=10.1002/humu.9350;
RA Snoeckx R.L., Hassan D.M., Kamal N.M., Van Den Bogaert K., Van Camp G.;
RT "Mutation analysis of the GJB2 (connexin 26) gene in Egypt.";
RL Hum. Mutat. 26:60-61(2005).
RN [48]
RP CHARACTERIZATION OF VARIANT DFNB1A LEU-84.
RX PubMed=15592461; DOI=10.1038/ncb1205;
RA Beltramello M., Piazza V., Bukauskas F.F., Pozzan T., Mammano F.;
RT "Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies
RT recessive hereditary deafness.";
RL Nat. Cell Biol. 7:63-69(2005).
RN [49]
RP CHARACTERIZATION OF VARIANT DFNB1A THR-34, PATHOGENIC ROLE OF VARIANT
RP DFNB1A THR-34, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16849369; DOI=10.1093/hmg/ddl184;
RA Bicego M., Beltramello M., Melchionda S., Carella M., Piazza V.,
RA Zelante L., Bukauskas F.F., Arslan E., Cama E., Pantano S., Bruzzone R.,
RA D'Andrea P., Mammano F.;
RT "Pathogenetic role of the deafness-related M34T mutation of Cx26.";
RL Hum. Mol. Genet. 15:2569-2587(2006).
RN [50]
RP VARIANTS DFNB1A THR-34 AND ILE-37.
RX PubMed=17935238; DOI=10.1002/ajmg.a.31982;
RA Pollak A., Skorka A., Mueller-Malesinska M., Kostrzewa G., Kisiel B.,
RA Waligora J., Krajewski P., Oldak M., Korniszewski L., Skarzynski H.,
RA Ploski R.;
RT "M34T and V37I mutations in GJB2 associated hearing impairment: evidence
RT for pathogenicity and reduced penetrance.";
RL Am. J. Med. Genet. A 143:2534-2543(2007).
RN [51]
RP VARIANT DFNB1A ASP-130.
RX PubMed=17666888; DOI=10.1097gim.0b013e3180a03276;
RA Putcha G.V., Bejjani B.A., Bleoo S., Booker J.K., Carey J.C., Carson N.,
RA Das S., Dempsey M.A., Gastier-Foster J.M., Greinwald J.H. Jr.,
RA Hoffmann M.L., Jeng L.J., Kenna M.A., Khababa I., Lilley M., Mao R.,
RA Muralidharan K., Otani I.M., Rehm H.L., Schaefer F., Seltzer W.K.,
RA Spector E.B., Springer M.A., Weck K.E., Wenstrup R.J., Withrow S., Wu B.L.,
RA Zariwala M.A., Schrijver I.;
RT "A multicenter study of the frequency and distribution of GJB2 and GJB6
RT mutations in a large North American cohort.";
RL Genet. Med. 9:413-426(2007).
RN [52]
RP VARIANT DFNB1A MET-84, AND CHARACTERIZATION OF VARIANT DFNB1A MET-84.
RX PubMed=17660464; DOI=10.1136/jmg.2007.050682;
RA Matos T.D., Caria H., Simoes-Teixeira H., Aasen T., Nickel R., Jagger D.J.,
RA O'Neill A., Kelsell D.P., Fialho G.;
RT "A novel hearing-loss-related mutation occurring in the GJB2 basal
RT promoter.";
RL J. Med. Genet. 44:721-725(2007).
RN [53]
RP VARIANT PPKDFN ARG-73, AND CHARACTERIZATION OF VARIANT PPKDFN ARG-73.
RX PubMed=17993581; DOI=10.1136/jmg.2007.052332;
RA de Zwart-Storm E.A., Hamm H., Stoevesandt J., Steijlen P.M., Martin P.E.,
RA van Geel M., van Steensel M.A.M.;
RT "A novel missense mutation in GJB2 disturbs gap junction protein transport
RT and causes focal palmoplantar keratoderma with deafness.";
RL J. Med. Genet. 45:161-166(2008).
RN [54]
RP VARIANT ARG-168.
RX PubMed=19283857; DOI=10.1002/ajmg.a.32765;
RA Alexandrino F., de Oliveira C.A., Magalhaes R.F., Florence M.E.,
RA de Souza E.M., Sartorato E.L.;
RT "Connexin mutations in Brazilian patients with skin disorders with or
RT without hearing loss.";
RL Am. J. Med. Genet. A 149:681-684(2009).
RN [55]
RP VARIANT VOWNKL VAL-130.
RX PubMed=18688874; DOI=10.1002/ajmg.a.32462;
RA Iossa S., Chinetti V., Auletta G., Laria C., De Luca M., Rienzo M.,
RA Giannini P., Delfino M., Ciccodicola A., Marciano E., Franze A.;
RT "New evidence for the correlation of the p.G130V mutation in the GJB2 gene
RT and syndromic hearing loss with palmoplantar keratoderma.";
RL Am. J. Med. Genet. A 149:685-688(2009).
RN [56]
RP VARIANT ILE-27.
RX PubMed=19416251; DOI=10.1111/j.1365-2133.2009.09137.x;
RA Nemoto-Hasebe I., Akiyama M., Kudo S., Ishiko A., Tanaka A., Arita K.,
RA Shimizu H.;
RT "Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies
RT palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing
RT loss.";
RL Br. J. Dermatol. 161:452-455(2009).
RN [57]
RP VARIANT DFNA3A GLU-46, VARIANT DFNB1A ARG-86, CHARACTERIZATION OF VARIANT
RP DFNA3A GLU-46, CHARACTERIZATION OF VARIANT DFNB1A ARG-86, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19384972; DOI=10.1002/humu.21036;
RA Choi S.-Y., Park H.-J., Lee K.Y., Dinh E.H., Chang Q., Ahmad S., Lee S.H.,
RA Bok J., Lin X., Kim U.-K.;
RT "Different functional consequences of two missense mutations in the GJB2
RT gene associated with non-syndromic hearing loss.";
RL Hum. Mutat. 30:E716-E727(2009).
RN [58]
RP VARIANTS DFNB1A ILE-37 AND ALA-130.
RX PubMed=23680645; DOI=10.1016/j.gene.2013.04.078;
RA Riahi Z., Hammami H., Ouragini H., Messai H., Zainine R., Bouyacoub Y.,
RA Romdhane L., Essaid D., Kefi R., Rhimi M., Bedoui M., Dhaouadi A.,
RA Feldmann D., Jonard L., Besbes G., Abdelhak S.;
RT "Update of the spectrum of GJB2 gene mutations in Tunisian families with
RT autosomal recessive nonsyndromic hearing loss.";
RL Gene 525:1-4(2013).
RN [59]
RP INVOLVEMENT IN DFNB1A.
RX PubMed=28281779; DOI=10.1089/gtmb.2016.0328;
RA Wang R., Han S., Khan A., Zhang X.;
RT "Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or
RT Syndromic Hearing Loss.";
RL Genet. Test. Mol. Biomarkers 21:316-321(2017).
RN [60]
RP VARIANT DFNB1A 24-TRP--VAL-226 DEL.
RX PubMed=30872814; DOI=10.1038/s41431-019-0372-y;
RA Schrauwen I., Melegh B.I., Chakchouk I., Acharya A., Nasir A., Poston A.,
RA Cornejo-Sanchez D.M., Szabo Z., Karosi T., Bene J., Melegh B., Leal S.M.;
RT "Hearing impairment locus heterogeneity and identification of PLS1 as a new
RT autosomal dominant gene in Hungarian Roma.";
RL Eur. J. Hum. Genet. 27:869-878(2019).
RN [61]
RP CONFIRMED PATHOGENICITY OF VARIANTS DFNB1A THR-34 AND ILE-37.
RX PubMed=31160754; DOI=10.1038/s41436-019-0535-9;
RG ClinGen Hearing Loss Working Group;
RA Shen J., Oza A.M., Del Castillo I., Duzkale H., Matsunaga T., Pandya A.,
RA Kang H.P., Mar-Heyming R., Guha S., Moyer K., Lo C., Kenna M.,
RA Alexander J.J., Zhang Y., Hirsch Y., Luo M., Cao Y., Wai Choy K.,
RA Cheng Y.F., Avraham K.B., Hu X., Garrido G., Moreno-Pelayo M.A.,
RA Greinwald J., Zhang K., Zeng Y., Brownstein Z., Basel-Salmon L.,
RA Davidov B., Frydman M., Weiden T., Nagan N., Willis A., Hemphill S.E.,
RA Grant A.R., Siegert R.K., DiStefano M.T., Amr S.S., Rehm H.L.,
RA Abou Tayoun A.N.;
RT "Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2
RT by the ClinGen Hearing Loss Expert Panel.";
RL Genet. Med. 21:2442-2452(2019).
CC -!- FUNCTION: Structural component of gap junctions (PubMed:17551008,
CC PubMed:19340074, PubMed:21094651, PubMed:26753910, PubMed:16849369,
CC PubMed:19384972). Gap junctions are dodecameric channels that connect
CC the cytoplasm of adjoining cells. They are formed by the docking of two
CC hexameric hemichannels, one from each cell membrane (PubMed:17551008,
CC PubMed:19340074, PubMed:21094651, PubMed:26753910). Small molecules and
CC ions diffuse from one cell to a neighboring cell via the central pore
CC (PubMed:21094651, PubMed:16849369, PubMed:19384972).
CC {ECO:0000269|PubMed:16849369, ECO:0000269|PubMed:17551008,
CC ECO:0000269|PubMed:19340074, ECO:0000269|PubMed:19384972,
CC ECO:0000269|PubMed:21094651, ECO:0000269|PubMed:26753910}.
CC -!- SUBUNIT: A hemichannel or connexon is composed of a hexamer of
CC connexins. A functional gap junction is formed by the apposition of two
CC hemichannels (PubMed:17551008, PubMed:19340074, PubMed:21094651,
CC PubMed:26753910). Interacts with CNST (PubMed:19864490). Forms
CC heteromeric channels with GJB4 (By similarity).
CC {ECO:0000250|UniProtKB:Q00977, ECO:0000269|PubMed:17551008,
CC ECO:0000269|PubMed:19340074, ECO:0000269|PubMed:19864490,
CC ECO:0000269|PubMed:21094651, ECO:0000269|PubMed:26753910}.
CC -!- INTERACTION:
CC P29033; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-3905204, EBI-19125216;
CC P29033; P35414: APLNR; NbExp=3; IntAct=EBI-3905204, EBI-2875891;
CC P29033; Q13520: AQP6; NbExp=3; IntAct=EBI-3905204, EBI-13059134;
CC P29033; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-3905204, EBI-11343438;
CC P29033; Q15125: EBP; NbExp=3; IntAct=EBI-3905204, EBI-3915253;
CC P29033; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-3905204, EBI-781551;
CC P29033; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-3905204, EBI-18304435;
CC P29033; O15552: FFAR2; NbExp=3; IntAct=EBI-3905204, EBI-2833872;
CC P29033; P36382: GJA5; NbExp=3; IntAct=EBI-3905204, EBI-750433;
CC P29033; P48165: GJA8; NbExp=3; IntAct=EBI-3905204, EBI-17458373;
CC P29033; P08034: GJB1; NbExp=3; IntAct=EBI-3905204, EBI-17565645;
CC P29033; P29033: GJB2; NbExp=4; IntAct=EBI-3905204, EBI-3905204;
CC P29033; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-3905204, EBI-13345167;
CC P29033; O15529: GPR42; NbExp=3; IntAct=EBI-3905204, EBI-18076404;
CC P29033; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-3905204, EBI-18053395;
CC P29033; O95279: KCNK5; NbExp=3; IntAct=EBI-3905204, EBI-3934936;
CC P29033; P26715: KLRC1; NbExp=3; IntAct=EBI-3905204, EBI-9018187;
CC P29033; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-3905204, EBI-2820517;
CC P29033; Q9HCJ2: LRRC4C; NbExp=3; IntAct=EBI-3905204, EBI-3925442;
CC P29033; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-3905204, EBI-2858252;
CC P29033; Q96DS6: MS4A6E; NbExp=3; IntAct=EBI-3905204, EBI-17931225;
CC P29033; O00623: PEX12; NbExp=3; IntAct=EBI-3905204, EBI-594836;
CC P29033; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-3905204, EBI-373552;
CC P29033; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-3905204, EBI-3920694;
CC P29033; Q3SXP7: SHISAL1; NbExp=3; IntAct=EBI-3905204, EBI-18037857;
CC P29033; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-3905204, EBI-17595455;
CC P29033; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-3905204, EBI-8644112;
CC P29033; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-3905204, EBI-17280858;
CC P29033; Q0VAB0: TBXA2R; NbExp=3; IntAct=EBI-3905204, EBI-18271435;
CC P29033; Q8N6K0: TEX29; NbExp=3; IntAct=EBI-3905204, EBI-19027521;
CC P29033; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-3905204, EBI-6268651;
CC P29033; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-3905204, EBI-12947623;
CC P29033; Q9BX73: TM2D2; NbExp=3; IntAct=EBI-3905204, EBI-7054664;
CC P29033; Q96A25: TMEM106A; NbExp=3; IntAct=EBI-3905204, EBI-3915978;
CC P29033; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-3905204, EBI-10982110;
CC P29033; Q9Y320: TMX2; NbExp=3; IntAct=EBI-3905204, EBI-6447886;
CC P29033; P34981: TRHR; NbExp=3; IntAct=EBI-3905204, EBI-18055230;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16849369,
CC ECO:0000269|PubMed:17551008, ECO:0000269|PubMed:19340074,
CC ECO:0000269|PubMed:19384972, ECO:0000269|PubMed:21094651,
CC ECO:0000269|PubMed:26753910}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17551008, ECO:0000269|PubMed:19340074,
CC ECO:0000269|PubMed:21094651, ECO:0000269|PubMed:26753910}. Cell
CC junction, gap junction {ECO:0000269|PubMed:16849369,
CC ECO:0000269|PubMed:17551008, ECO:0000269|PubMed:19340074,
CC ECO:0000269|PubMed:19384972, ECO:0000269|PubMed:21094651,
CC ECO:0000269|PubMed:26753910}. Note=Colocalizes with GJB4 at gap
CC junction plaques in the cochlea. {ECO:0000250|UniProtKB:Q00977}.
CC -!- DISEASE: Deafness, autosomal recessive, 1A (DFNB1A) [MIM:220290]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner ear,
CC the nerve pathways to the brain, or the area of the brain that receives
CC sound information. {ECO:0000269|PubMed:10830906,
CC ECO:0000269|PubMed:11313763, ECO:0000269|PubMed:11439000,
CC ECO:0000269|PubMed:12121355, ECO:0000269|PubMed:12239718,
CC ECO:0000269|PubMed:12786758, ECO:0000269|PubMed:14694360,
CC ECO:0000269|PubMed:14722929, ECO:0000269|PubMed:15592461,
CC ECO:0000269|PubMed:15666300, ECO:0000269|PubMed:15994881,
CC ECO:0000269|PubMed:16849369, ECO:0000269|PubMed:17660464,
CC ECO:0000269|PubMed:17666888, ECO:0000269|PubMed:17935238,
CC ECO:0000269|PubMed:19384972, ECO:0000269|PubMed:23680645,
CC ECO:0000269|PubMed:28281779, ECO:0000269|PubMed:30872814,
CC ECO:0000269|PubMed:31160754, ECO:0000269|PubMed:9139825,
CC ECO:0000269|PubMed:9328482, ECO:0000269|PubMed:9336442,
CC ECO:0000269|PubMed:9422505, ECO:0000269|PubMed:9471561,
CC ECO:0000269|PubMed:9529365, ECO:0000269|PubMed:9600457}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Deafness, autosomal dominant, 3A (DFNA3A) [MIM:601544]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:10807696, ECO:0000269|PubMed:11313763,
CC ECO:0000269|PubMed:11439000, ECO:0000269|PubMed:12668604,
CC ECO:0000269|PubMed:12786758, ECO:0000269|PubMed:19384972,
CC ECO:0000269|PubMed:9620796}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Vohwinkel syndrome (VOWNKL) [MIM:124500]: An autosomal
CC dominant disease characterized by hyperkeratosis, constriction on
CC fingers and toes and congenital deafness. {ECO:0000269|PubMed:10369869,
CC ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:15954104,
CC ECO:0000269|PubMed:18688874}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Keratoderma, palmoplantar, with deafness (PPKDFN)
CC [MIM:148350]: An autosomal dominant disorder characterized by the
CC association of palmoplantar hyperkeratosis with progressive, bilateral,
CC high-frequency, sensorineural deafness. {ECO:0000269|PubMed:10633135,
CC ECO:0000269|PubMed:10757647, ECO:0000269|PubMed:12372058,
CC ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:15996214,
CC ECO:0000269|PubMed:17993581, ECO:0000269|PubMed:9856479}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Keratitis-ichthyosis-deafness syndrome, autosomal dominant
CC (KIDAD) [MIM:148210]: An autosomal dominant form of keratitis-
CC ichthyosis-deafness syndrome, a disease characterized by the
CC association of hyperkeratotic skin lesions with vascularizing keratitis
CC and profound sensorineural hearing loss. Clinical features include
CC deafness, ichthyosis, photophobia, absent or decreased eyebrows, sparse
CC or absent scalp hair, decreased sweating and dysplastic finger and
CC toenails. {ECO:0000269|PubMed:11912510, ECO:0000269|PubMed:12548749,
CC ECO:0000269|PubMed:12752120}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Bart-Pumphrey syndrome (BAPS) [MIM:149200]: An autosomal
CC dominant disorder characterized by sensorineural hearing loss,
CC palmoplantar keratoderma, knuckle pads, and leukonychia, It shows
CC considerable phenotypic variability. {ECO:0000269|PubMed:15482471,
CC ECO:0000269|PubMed:15952212}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Ichthyosis hystrix-like with deafness syndrome (HID syndrome)
CC [MIM:602540]: An autosomal dominant keratinizing disorder characterized
CC by sensorineural deafness and spiky hyperkeratosis affecting the entire
CC skin. HID syndrome is considered to differ from the similar KID
CC syndrome in the extent and time of occurrence of skin symptoms and the
CC severity of the associated keratitis. {ECO:0000269|PubMed:12072059}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the connexin family. Beta-type (group I)
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The role of Thr-34 and Ile-37 variants in deafness was unclear
CC (PubMed:9139825, PubMed:9422505, PubMed:14694360, PubMed:17935238 and
CC PubMed:16849369). However, their pathogenicity has been definitely
CC confirmed (PubMed:31160754).
CC -!- WEB RESOURCE: Name=Connexin-deafness homepage;
CC URL="http://perelman.crg.es/deafness/";
CC -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page;
CC URL="https://hereditaryhearingloss.org/dominant-genes";
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DR EMBL; M86849; AAD21314.1; -; mRNA.
DR EMBL; AF281280; AAF91440.1; -; Genomic_DNA.
DR EMBL; AF479776; AAL87696.1; -; Genomic_DNA.
DR EMBL; AY255853; AAP34178.1; -; Genomic_DNA.
DR EMBL; AY275646; AAQ94940.1; -; Genomic_DNA.
DR EMBL; AY275647; AAQ94941.1; -; Genomic_DNA.
DR EMBL; AY275648; AAQ94942.1; -; Genomic_DNA.
DR EMBL; AY275649; AAQ94943.1; -; Genomic_DNA.
DR EMBL; AY275650; AAQ94944.1; -; Genomic_DNA.
DR EMBL; AY275651; AAQ94945.1; -; Genomic_DNA.
DR EMBL; AY275652; AAQ94946.1; -; Genomic_DNA.
DR EMBL; AY275653; AAQ94947.1; -; Genomic_DNA.
DR EMBL; AY275654; AAQ94948.1; -; Genomic_DNA.
DR EMBL; AY280971; AAQ17213.1; -; Genomic_DNA.
DR EMBL; AY953438; AAY25169.1; -; Genomic_DNA.
DR EMBL; AY953441; AAY25170.1; -; Genomic_DNA.
DR EMBL; BT006732; AAP35378.1; -; mRNA.
DR EMBL; AL138688; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017048; AAH17048.1; -; mRNA.
DR EMBL; BC071703; AAH71703.1; -; mRNA.
DR CCDS; CCDS9290.1; -.
DR PIR; A43424; A43424.
DR RefSeq; NP_003995.2; NM_004004.5.
DR RefSeq; XP_011533351.1; XM_011535049.2.
DR PDB; 2ZW3; X-ray; 3.50 A; A/B/C/D/E/F=1-226.
DR PDB; 3IZ1; EM; 6.00 A; A/B/C=1-226.
DR PDB; 3IZ2; EM; 10.00 A; A/B/C=8-226.
DR PDB; 5ER7; X-ray; 3.29 A; A/B=1-226.
DR PDB; 5ERA; X-ray; 3.80 A; A/B=1-226.
DR PDB; 5KJ3; NMR; -; A=1-22.
DR PDB; 5KJG; NMR; -; A=1-22.
DR PDB; 6UVR; EM; 4.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 6UVS; EM; 4.20 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 6UVT; EM; 7.50 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 7QEQ; EM; 1.90 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 7QER; EM; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 7QET; EM; 2.10 A; A/B/C/D/E/F/G/H/I/J/K/L=1-226.
DR PDB; 7QEW; EM; 2.10 A; G/H/I/J/K/L=1-226.
DR PDBsum; 2ZW3; -.
DR PDBsum; 3IZ1; -.
DR PDBsum; 3IZ2; -.
DR PDBsum; 5ER7; -.
DR PDBsum; 5ERA; -.
DR PDBsum; 5KJ3; -.
DR PDBsum; 5KJG; -.
DR PDBsum; 6UVR; -.
DR PDBsum; 6UVS; -.
DR PDBsum; 6UVT; -.
DR PDBsum; 7QEQ; -.
DR PDBsum; 7QER; -.
DR PDBsum; 7QET; -.
DR PDBsum; 7QEW; -.
DR AlphaFoldDB; P29033; -.
DR SMR; P29033; -.
DR BioGRID; 108972; 69.
DR CORUM; P29033; -.
DR DIP; DIP-59742N; -.
DR IntAct; P29033; 50.
DR STRING; 9606.ENSP00000372295; -.
DR BindingDB; P29033; -.
DR ChEMBL; CHEMBL4295738; -.
DR TCDB; 1.A.24.1.3; the gap junction-forming connexin (connexin) family.
DR iPTMnet; P29033; -.
DR PhosphoSitePlus; P29033; -.
DR BioMuta; GJB2; -.
DR DMDM; 77416855; -.
DR jPOST; P29033; -.
DR MassIVE; P29033; -.
DR PaxDb; P29033; -.
DR PeptideAtlas; P29033; -.
DR PRIDE; P29033; -.
DR ProteomicsDB; 54514; -.
DR ABCD; P29033; 1 sequenced antibody.
DR Antibodypedia; 4587; 337 antibodies from 37 providers.
DR DNASU; 2706; -.
DR Ensembl; ENST00000382844.2; ENSP00000372295.1; ENSG00000165474.8.
DR Ensembl; ENST00000382848.5; ENSP00000372299.4; ENSG00000165474.8.
DR GeneID; 2706; -.
DR KEGG; hsa:2706; -.
DR MANE-Select; ENST00000382848.5; ENSP00000372299.4; NM_004004.6; NP_003995.2.
DR UCSC; uc001umy.4; human.
DR CTD; 2706; -.
DR DisGeNET; 2706; -.
DR GeneCards; GJB2; -.
DR GeneReviews; GJB2; -.
DR HGNC; HGNC:4284; GJB2.
DR HPA; ENSG00000165474; Group enriched (esophagus, vagina).
DR MalaCards; GJB2; -.
DR MIM; 121011; gene.
DR MIM; 124500; phenotype.
DR MIM; 148210; phenotype.
DR MIM; 148350; phenotype.
DR MIM; 149200; phenotype.
DR MIM; 220290; phenotype.
DR MIM; 601544; phenotype.
DR MIM; 602540; phenotype.
DR neXtProt; NX_P29033; -.
DR OpenTargets; ENSG00000165474; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 494; Keratoderma hereditarium mutilans.
DR Orphanet; 477; KID syndrome.
DR Orphanet; 2698; Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome.
DR Orphanet; 2202; Palmoplantar keratoderma-deafness syndrome.
DR Orphanet; 166286; Porokeratotic eccrine ostial and dermal duct nevus.
DR PharmGKB; PA28695; -.
DR VEuPathDB; HostDB:ENSG00000165474; -.
DR eggNOG; ENOG502QWM8; Eukaryota.
DR GeneTree; ENSGT01030000234513; -.
DR HOGENOM; CLU_037388_4_1_1; -.
DR InParanoid; P29033; -.
DR OMA; RKFMKGE; -.
DR OrthoDB; 1174178at2759; -.
DR PhylomeDB; P29033; -.
DR TreeFam; TF329606; -.
DR PathwayCommons; P29033; -.
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-190861; Gap junction assembly.
DR Reactome; R-HSA-190872; Transport of connexons to the plasma membrane.
DR SignaLink; P29033; -.
DR SIGNOR; P29033; -.
DR BioGRID-ORCS; 2706; 39 hits in 1071 CRISPR screens.
DR ChiTaRS; GJB2; human.
DR EvolutionaryTrace; P29033; -.
DR GeneWiki; GJB2; -.
DR GenomeRNAi; 2706; -.
DR Pharos; P29033; Tbio.
DR PRO; PR:P29033; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P29033; protein.
DR Bgee; ENSG00000165474; Expressed in gingival epithelium and 131 other tissues.
DR ExpressionAtlas; P29033; baseline and differential.
DR Genevisible; P29033; HS.
DR GO; GO:0097449; C:astrocyte projection; IEA:Ensembl.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005922; C:connexin complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; TAS:Reactome.
DR GO; GO:0005921; C:gap junction; IDA:ARUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005243; F:gap junction channel activity; IDA:UniProtKB.
DR GO; GO:1903763; F:gap junction channel activity involved in cell communication by electrical coupling; IDA:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:1905867; P:epididymis development; IEA:Ensembl.
DR GO; GO:0016264; P:gap junction assembly; IDA:ARUK-UCL.
DR GO; GO:1990349; P:gap junction-mediated intercellular transport; IDA:UniProtKB.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IDA:ARUK-UCL.
DR Gene3D; 1.20.1440.80; -; 1.
DR InterPro; IPR000500; Connexin.
DR InterPro; IPR002268; Connexin26.
DR InterPro; IPR019570; Connexin_CCC.
DR InterPro; IPR017990; Connexin_CS.
DR InterPro; IPR013092; Connexin_N.
DR InterPro; IPR038359; Connexin_N_sf.
DR PANTHER; PTHR11984; PTHR11984; 1.
DR Pfam; PF00029; Connexin; 1.
DR PRINTS; PR00206; CONNEXIN.
DR PRINTS; PR01139; CONNEXINB2.
DR SMART; SM00037; CNX; 1.
DR SMART; SM01089; Connexin_CCC; 1.
DR PROSITE; PS00407; CONNEXINS_1; 1.
DR PROSITE; PS00408; CONNEXINS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell junction; Cell membrane; Deafness;
KW Disease variant; Disulfide bond; Ectodermal dysplasia; Gap junction;
KW Hearing; Ichthyosis; Membrane; Metal-binding; Non-syndromic deafness;
KW Palmoplantar keratoderma; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..226
FT /note="Gap junction beta-2 protein"
FT /id="PRO_0000057855"
FT INTRAMEM 2..13
FT /evidence="ECO:0000269|PubMed:26753910"
FT TOPO_DOM 14..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TRANSMEM 21..40
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TOPO_DOM 41..73
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TOPO_DOM 95..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TOPO_DOM 157..189
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26753910"
FT TOPO_DOM 211..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26753910"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:26753910,
FT ECO:0007744|PDB:5ER7"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:26753910,
FT ECO:0007744|PDB:5ER7"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:26753910,
FT ECO:0007744|PDB:5ER7"
FT DISULFID 53..180
FT /evidence="ECO:0000269|PubMed:19340074,
FT ECO:0000269|PubMed:26753910, ECO:0007744|PDB:2ZW3,
FT ECO:0007744|PDB:5ER7, ECO:0007744|PDB:5ERA"
FT DISULFID 60..174
FT /evidence="ECO:0000269|PubMed:19340074,
FT ECO:0000269|PubMed:26753910, ECO:0007744|PDB:2ZW3,
FT ECO:0007744|PDB:5ER7, ECO:0007744|PDB:5ERA"
FT DISULFID 64..169
FT /evidence="ECO:0000269|PubMed:19340074,
FT ECO:0000269|PubMed:26753910, ECO:0007744|PDB:2ZW3,
FT ECO:0007744|PDB:5ER7, ECO:0007744|PDB:5ERA"
FT VARIANT 12
FT /note="G -> R (in KIDAD; dbSNP:rs104894408)"
FT /evidence="ECO:0000269|PubMed:11912510"
FT /id="VAR_015453"
FT VARIANT 17
FT /note="S -> F (in KIDAD; dbSNP:rs28929485)"
FT /evidence="ECO:0000269|PubMed:11912510"
FT /id="VAR_015454"
FT VARIANT 24..226
FT /note="Missing (in DFNB1A)"
FT /evidence="ECO:0000269|PubMed:30872814"
FT /id="VAR_083826"
FT VARIANT 27
FT /note="V -> I (in dbSNP:rs2274084)"
FT /evidence="ECO:0000269|PubMed:10607953,
FT ECO:0000269|PubMed:12560944, ECO:0000269|PubMed:12746422,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15666300,
FT ECO:0000269|PubMed:19416251, ECO:0000269|PubMed:9529365"
FT /id="VAR_002137"
FT VARIANT 32
FT /note="R -> H (in DFNB1A; dbSNP:rs111033190)"
FT /evidence="ECO:0000269|PubMed:15666300"
FT /id="VAR_023605"
FT VARIANT 32
FT /note="R -> L (in dbSNP:rs111033190)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_016839"
FT VARIANT 34
FT /note="M -> T (in DFNB1A; it is correctly synthesized and
FT targeted to the plasma membrane; it inefficiently forms
FT intercellular channels that display an abnormal electrical
FT behavior; dbSNP:rs35887622)"
FT /evidence="ECO:0000269|PubMed:14694360,
FT ECO:0000269|PubMed:16849369, ECO:0000269|PubMed:17935238,
FT ECO:0000269|PubMed:31160754, ECO:0000269|PubMed:9139825,
FT ECO:0000269|PubMed:9600457"
FT /id="VAR_002138"
FT VARIANT 37
FT /note="V -> I (in DFNB1A; dbSNP:rs72474224)"
FT /evidence="ECO:0000269|PubMed:10607953,
FT ECO:0000269|PubMed:10830906, ECO:0000269|PubMed:12121355,
FT ECO:0000269|PubMed:12560944, ECO:0000269|PubMed:12786758,
FT ECO:0000269|PubMed:14722929, ECO:0000269|PubMed:17935238,
FT ECO:0000269|PubMed:23680645, ECO:0000269|PubMed:31160754,
FT ECO:0000269|PubMed:9529365"
FT /id="VAR_002139"
FT VARIANT 44
FT /note="W -> C (in DFNA3A; dbSNP:rs104894407)"
FT /evidence="ECO:0000269|PubMed:9620796"
FT /id="VAR_008709"
FT VARIANT 44
FT /note="W -> S (in DFNA3A; does not affect protein
FT trafficking; affects the ability to form functional
FT channels; dominant negative effect; dbSNP:rs104894413)"
FT /evidence="ECO:0000269|PubMed:12668604"
FT /id="VAR_032749"
FT VARIANT 45
FT /note="G -> E (in deafness; dbSNP:rs72561723)"
FT /evidence="ECO:0000269|PubMed:12560944"
FT /id="VAR_015455"
FT VARIANT 46..48
FT /note="DEQ -> E (may contribute to deafness)"
FT /evidence="ECO:0000269|PubMed:14722929"
FT /id="VAR_023606"
FT VARIANT 46
FT /note="D -> E (in DFNA3A; the mutant is targeted to the
FT plasma membrane but fails to transfer ionic calcium or
FT propidium iodide intercellularly suggesting disruption of
FT both ionic and biochemical coupling; heterozygous gap
FT junctions also show dysfunctional intercellular couplings
FT and hemichannel opening confirming the dominant-negative
FT nature of the mutation)"
FT /evidence="ECO:0000269|PubMed:19384972"
FT /id="VAR_060798"
FT VARIANT 50
FT /note="D -> N (in KIDAD and HID syndrome;
FT dbSNP:rs28931594)"
FT /evidence="ECO:0000269|PubMed:11912510,
FT ECO:0000269|PubMed:12072059, ECO:0000269|PubMed:12548749,
FT ECO:0000269|PubMed:12752120"
FT /id="VAR_015456"
FT VARIANT 50
FT /note="D -> Y (in KIDAD; dbSNP:rs28931594)"
FT /evidence="ECO:0000269|PubMed:12752120"
FT /id="VAR_015935"
FT VARIANT 54
FT /note="N -> K (in BAPS; dbSNP:rs104894412)"
FT /evidence="ECO:0000269|PubMed:15482471"
FT /id="VAR_032750"
FT VARIANT 59
FT /note="G -> A (in PPKDFN; impairs trafficking; localizes
FT intracellularly closed to the nucleus; affects the ability
FT to form functional channels; phenotype can be rescued by
FT coexpression with wild-type protein; dbSNP:rs104894404)"
FT /evidence="ECO:0000269|PubMed:10633135,
FT ECO:0000269|PubMed:12668604"
FT /id="VAR_009965"
FT VARIANT 59
FT /note="G -> S (in BAPS; dbSNP:rs104894410)"
FT /evidence="ECO:0000269|PubMed:15952212"
FT /id="VAR_032751"
FT VARIANT 66
FT /note="D -> H (in VOWNKL and PPKDFN; impairs trafficking;
FT localizes intracellularly closed to the nucleus; affects
FT the ability to form functional channels; phenotype can be
FT rescued by coexpression with wild-type protein;
FT dbSNP:rs104894403)"
FT /evidence="ECO:0000269|PubMed:10369869,
FT ECO:0000269|PubMed:10757647, ECO:0000269|PubMed:12668604"
FT /id="VAR_008710"
FT VARIANT 71
FT /note="I -> T (in deafness; dbSNP:rs1373154561)"
FT /evidence="ECO:0000269|PubMed:12560944"
FT /id="VAR_015457"
FT VARIANT 73
FT /note="H -> R (in PPKDFN; the mutant has a dominant-
FT negative effect on connexin trafficking;
FT dbSNP:rs121912968)"
FT /evidence="ECO:0000269|PubMed:17993581"
FT /id="VAR_060799"
FT VARIANT 75
FT /note="R -> Q (in PPKDFN; the mutant protein completely
FT prevents the formation of functional channels;
FT dbSNP:rs28931593)"
FT /evidence="ECO:0000269|PubMed:12372058,
FT ECO:0000269|PubMed:15996214"
FT /id="VAR_015936"
FT VARIANT 75
FT /note="R -> W (in PPKDFN and DFNA3A; does not affect
FT protein trafficking; affects the ability to form functional
FT channels; dominant negative effect; dbSNP:rs104894402)"
FT /evidence="ECO:0000269|PubMed:12668604,
FT ECO:0000269|PubMed:9856479"
FT /id="VAR_002140"
FT VARIANT 77
FT /note="W -> R (in DFNB1A; dbSNP:rs104894397)"
FT /evidence="ECO:0000269|PubMed:9328482"
FT /id="VAR_002141"
FT VARIANT 79
FT /note="L -> P (in DFNB1A; dbSNP:rs1555341957)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023607"
FT VARIANT 80
FT /note="Q -> K (in DFNB1A)"
FT /evidence="ECO:0000269|PubMed:15666300"
FT /id="VAR_023608"
FT VARIANT 83
FT /note="F -> L (in dbSNP:rs111033218)"
FT /evidence="ECO:0000269|PubMed:9600457"
FT /id="VAR_002142"
FT VARIANT 84
FT /note="V -> L (in DFNB1A; sorted to the plasma membrane
FT normally and forms gap junctions that were morphologically
FT and electrically indistinguishable from those of control;
FT the mutation reduces the permeability of GJB2 gap junction
FT channels to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3),
FT resulting in blockade of the Ins(1,4,5)P3-induced inward
FT calcium current in neighboring cells; dbSNP:rs104894409)"
FT /evidence="ECO:0000269|PubMed:15592461,
FT ECO:0000269|PubMed:9529365"
FT /id="VAR_002143"
FT VARIANT 84
FT /note="V -> M (in DFNB1A; the mutant disrupts cellular
FT communication; dbSNP:rs104894409)"
FT /evidence="ECO:0000269|PubMed:17660464"
FT /id="VAR_060800"
FT VARIANT 86
FT /note="T -> R (in DFNB1A; does not form gap junctions since
FT the mutated protein is confined in the cytoplasm and not
FT transported to the cell membrane; when the mutation is
FT coexpressed with the wild-type protein ionic and
FT biochemical coupling is normal consistent with the
FT recessive nature of the mutation; dbSNP:rs1291519904)"
FT /evidence="ECO:0000269|PubMed:12560944,
FT ECO:0000269|PubMed:19384972"
FT /id="VAR_015458"
FT VARIANT 90
FT /note="L -> P (in DFNB1A; dbSNP:rs80338945)"
FT /evidence="ECO:0000269|PubMed:10830906,
FT ECO:0000269|PubMed:11313763"
FT /id="VAR_015937"
FT VARIANT 93
FT /note="M -> I (in DFNB1A; dbSNP:rs397516871)"
FT /evidence="ECO:0000269|PubMed:15666300"
FT /id="VAR_023609"
FT VARIANT 95
FT /note="V -> M (in DFNB1A; dbSNP:rs111033299)"
FT /evidence="ECO:0000269|PubMed:9529365"
FT /id="VAR_002144"
FT VARIANT 111
FT /note="I -> T (in dbSNP:rs1316789942)"
FT /evidence="ECO:0000269|PubMed:12746422"
FT /id="VAR_015938"
FT VARIANT 113
FT /note="S -> R (in DFNB1A; dbSNP:rs80338946)"
FT /evidence="ECO:0000269|PubMed:9529365"
FT /id="VAR_002145"
FT VARIANT 114
FT /note="E -> G (in dbSNP:rs2274083)"
FT /evidence="ECO:0000269|PubMed:10607953,
FT ECO:0000269|PubMed:12560944, ECO:0000269|PubMed:12746422,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15666300"
FT /id="VAR_009966"
FT VARIANT 117
FT /note="D -> H"
FT /evidence="ECO:0000269|PubMed:15954104"
FT /id="VAR_069519"
FT VARIANT 118
FT /note="Missing (in DFNB1A)"
FT /id="VAR_060801"
FT VARIANT 120
FT /note="Missing (in DFNB1A)"
FT /evidence="ECO:0000269|PubMed:15666300"
FT /id="VAR_023610"
FT VARIANT 123
FT /note="T -> N (in dbSNP:rs111033188)"
FT /evidence="ECO:0000269|PubMed:12560944"
FT /id="VAR_015459"
FT VARIANT 127
FT /note="R -> H (in dbSNP:rs111033196)"
FT /evidence="ECO:0000269|PubMed:12746422,
FT ECO:0000269|PubMed:14722929, ECO:0000269|PubMed:15666300"
FT /id="VAR_015939"
FT VARIANT 129
FT /note="E -> K (in DFNB1A; dbSNP:rs397516875)"
FT /evidence="ECO:0000269|PubMed:15666300"
FT /id="VAR_023611"
FT VARIANT 130
FT /note="G -> A (in DFNB1A; dbSNP:rs779018464)"
FT /evidence="ECO:0000269|PubMed:23680645"
FT /id="VAR_069520"
FT VARIANT 130
FT /note="G -> D (in DFNB1A; dbSNP:rs779018464)"
FT /evidence="ECO:0000269|PubMed:17666888"
FT /id="VAR_069521"
FT VARIANT 130
FT /note="G -> V (in VOWNKL)"
FT /evidence="ECO:0000269|PubMed:15954104,
FT ECO:0000269|PubMed:18688874"
FT /id="VAR_069522"
FT VARIANT 142
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:15954104"
FT /id="VAR_069523"
FT VARIANT 143
FT /note="R -> Q (in DFNA3A; dbSNP:rs104894401)"
FT /evidence="ECO:0000269|PubMed:11313763"
FT /id="VAR_015940"
FT VARIANT 143
FT /note="R -> W (in DFNB1A; dbSNP:rs80338948)"
FT /evidence="ECO:0000269|PubMed:11439000,
FT ECO:0000269|PubMed:12560944, ECO:0000269|PubMed:15666300,
FT ECO:0000269|PubMed:9471561"
FT /id="VAR_015460"
FT VARIANT 148
FT /note="A -> P"
FT /evidence="ECO:0000269|PubMed:15954104"
FT /id="VAR_069524"
FT VARIANT 153
FT /note="V -> I (may contribute to deafness;
FT dbSNP:rs111033186)"
FT /evidence="ECO:0000269|PubMed:12746422,
FT ECO:0000269|PubMed:14722929, ECO:0000269|PubMed:15666300"
FT /id="VAR_009967"
FT VARIANT 159
FT /note="D -> V (in DFNB1A; dbSNP:rs28931592)"
FT /evidence="ECO:0000269|PubMed:12239718"
FT /id="VAR_015941"
FT VARIANT 160
FT /note="G -> S (in dbSNP:rs34988750)"
FT /evidence="ECO:0000269|PubMed:14722929,
FT ECO:0000269|PubMed:9600457"
FT /id="VAR_002146"
FT VARIANT 165
FT /note="R -> W (in dbSNP:rs376898963)"
FT /evidence="ECO:0000269|PubMed:12746422"
FT /id="VAR_015942"
FT VARIANT 167
FT /note="V -> M (may contribute to deafness;
FT dbSNP:rs111033360)"
FT /evidence="ECO:0000269|PubMed:14722929"
FT /id="VAR_023612"
FT VARIANT 168
FT /note="K -> R (in a patient with congenital
FT erythrokeratodermia; unknown pathological significance;
FT dbSNP:rs200104362)"
FT /evidence="ECO:0000269|PubMed:19283857"
FT /id="VAR_057959"
FT VARIANT 169
FT /note="C -> Y (in dbSNP:rs774518779)"
FT /id="VAR_009968"
FT VARIANT 178
FT /note="V -> A (in DFNB1A; dbSNP:rs568612627)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023613"
FT VARIANT 179
FT /note="D -> N (in DFNA3A; dbSNP:rs28931595)"
FT /evidence="ECO:0000269|PubMed:12786758"
FT /id="VAR_032752"
FT VARIANT 184
FT /note="R -> P (in DFNB1A; dbSNP:rs80338950)"
FT /evidence="ECO:0000269|PubMed:15666300,
FT ECO:0000269|PubMed:9336442"
FT /id="VAR_015943"
FT VARIANT 184
FT /note="R -> Q (in DFNA3A; dbSNP:rs80338950)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023614"
FT VARIANT 184
FT /note="R -> W (in DFNB1A; dbSNP:rs998045226)"
FT /evidence="ECO:0000269|PubMed:10830906"
FT /id="VAR_009969"
FT VARIANT 191
FT /note="F -> L (in dbSNP:rs397516878)"
FT /evidence="ECO:0000269|PubMed:12560944"
FT /id="VAR_015461"
FT VARIANT 197
FT /note="A -> S (in DFNA3A; dbSNP:rs777236559)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023615"
FT VARIANT 202
FT /note="C -> F (in DFNA3A; dbSNP:rs104894406)"
FT /evidence="ECO:0000269|PubMed:10807696"
FT /id="VAR_015944"
FT VARIANT 203
FT /note="I -> K (in DFNB1A)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023616"
FT VARIANT 203
FT /note="I -> T (in dbSNP:rs76838169)"
FT /evidence="ECO:0000269|PubMed:10607953,
FT ECO:0000269|PubMed:12560944"
FT /id="VAR_009970"
FT VARIANT 214
FT /note="L -> P (in DFNB1A)"
FT /evidence="ECO:0000269|PubMed:11439000"
FT /id="VAR_023617"
FT MUTAGEN 2..10
FT /note="Missing: Strongly reduced insertion into the cell
FT membrane and strongly reduced gap junction plaque
FT assembly."
FT /evidence="ECO:0000269|PubMed:21094651"
FT MUTAGEN 2..7
FT /note="Missing: Loss of gap junction ion conductance."
FT /evidence="ECO:0000269|PubMed:21094651"
FT MUTAGEN 34
FT /note="M->A: Loss of gap junction ion conductance, probably
FT due to very low open probability of the channels. Can form
FT functional channels with wild-type, but with strongly
FT reduced channel conductance. No visible effect on channel
FT assembly and membrane insertion."
FT /evidence="ECO:0000269|PubMed:21094651"
FT CONFLICT 86
FT /note="T -> S (in Ref. 1; AAD21314)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="K -> N (in Ref. 4; AAY25170)"
FT /evidence="ECO:0000305"
FT HELIX 5..11
FT /evidence="ECO:0007829|PDB:2ZW3"
FT HELIX 21..41
FT /evidence="ECO:0007829|PDB:5ER7"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:5ER7"
FT TURN 47..50
FT /evidence="ECO:0007829|PDB:5ER7"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:5ER7"
FT HELIX 60..68
FT /evidence="ECO:0007829|PDB:5ER7"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:5ER7"
FT HELIX 87..94
FT /evidence="ECO:0007829|PDB:5ER7"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:2ZW3"
FT TURN 126..130
FT /evidence="ECO:0007829|PDB:2ZW3"
FT HELIX 136..155
FT /evidence="ECO:0007829|PDB:5ER7"
FT TURN 156..159
FT /evidence="ECO:0007829|PDB:5ER7"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2ZW3"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:5ER7"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:5ER7"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:5ER7"
FT HELIX 185..211
FT /evidence="ECO:0007829|PDB:5ER7"
SQ SEQUENCE 226 AA; 26215 MW; D35293C6747E908C CRC64;
MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC
KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV
