Reviewed, UniProtKB/Swiss-Prot P29033 (CXB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Gap junction beta-2 protein
Alternative name(s):
    Connexin-26
      Short name=Cx26

Gene names

Name:

GJB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	226 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
Subunit structure	A connexon is composed of a hexamer of connexins.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Polymorphism	The Thr-34 allele was originally (Ref.10) thought to be a cause of forms of hereditary non-syndromic sensorineural deafness (DFNA3 and DFNB1).
Involvement in disease	Defects in GJB2 are the cause of non-syndromic sensorineural deafness autosomal recessive type 1 (DFNB1) [MIM:220290]. DFNB1 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Ref.2 Ref.3 Ref.4 Ref.12 Ref.13 Ref.14 Ref.18 Ref.25 Ref.27 Ref.29 Ref.33 Defects in GJB2 are the cause of non-syndromic sensorineural deafness autosomal dominant type 3A (DFNA3A) [MIM:601544]. Defects in GJB2 are a cause of Vohwinkel syndrome (VS) [MIM:124500]. VS is an autosomal dominant disease characterized by hyperkeratosis, constriction on finger and toes and congenital deafness. Ref.35 Ref.19 Defects in GJB2 are a cause of palmoplantar keratoderma with deafness (PPKDFN) [MIM:148350]. PPKDFN is an autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness. Ref.35 Ref.15 Ref.21 Ref.23 Ref.30 Defects in GJB2 are a cause of keratitis-ichthyosis-deafness syndrome (KID syndrome) [MIM:148210]; an autosomal dominant form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. KID syndrome is characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails. Defects in GJB2 are the cause of Bart-Pumphrey syndrome (BPS) [MIM:149200]. BPS is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability. Ref.37 Ref.38 Defects in GJB2 are the cause of ichthyosis hystrix-like with deafness syndrome (HID syndrome) [MIM:602540]. HID syndrome is an autosomal-dominant inherited keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis.
Sequence similarities	Belongs to the connexin family. Beta-type (group I) subfamily.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Cell junction Cell membrane Gap junction Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Ectodermal dysplasia Ichthyosis Non-syndromic deafness Palmoplantar keratoderma
Domain	Transmembrane
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc sensory perception of sound Ref.10 Traceable author statement. Source: ProtInc transport Ref.1 Traceable author statement. Source: ProtInc
Cellular component	Golgi membrane Inferred from Experiment. Source: Reactome connexon complex Ref.1 Traceable author statement. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 226	226	Gap junction beta-2 protein		PRO_0000057855
Regions
	Topological domain	1 – 20	20	Cytoplasmic Potential
	Transmembrane	21 – 40	20	Potential
	Topological domain	41 – 75	35	Extracellular Potential
	Transmembrane	76 – 98	23	Potential
	Topological domain	99 – 131	33	Cytoplasmic Potential
	Transmembrane	132 – 154	23	Potential
	Topological domain	155 – 192	38	Extracellular Potential
	Transmembrane	193 – 215	23	Potential
	Topological domain	216 – 226	11	Cytoplasmic Potential
Natural variations
	Natural variant	12	1	G → R in KID syndrome.		VAR_015453
	Natural variant	17	1	S → F in KID syndrome. dbSNP rs28929485.		VAR_015454
	Natural variant	27	1	V → I: dbSNP rs2274084. Ref.4 Ref.14 Ref.9 Ref.20 Ref.34 Ref.36		VAR_002137
	Natural variant	32	1	R → H in DFNB1. Ref.4		VAR_023605
	Natural variant	32	1	R → L Ref.4 Ref.6		VAR_016839
	Natural variant	34	1	M → T: dbSNP rs35887622. Ref.10 Ref.11 Ref.16		VAR_002138
	Natural variant	37	1	V → I in DFNB1; was reported first as a polymorphism. Ref.3 Ref.29 Ref.33		VAR_002139
	Natural variant	44	1	W → C in DFNA3A.		VAR_008709
	Natural variant	44	1	W → S in DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect.		VAR_032749
	Natural variant	45	1	G → E in deafness. Ref.34		VAR_015455
	Natural variant	46 – 48	3	DEQ → E May contribute to deafness.		VAR_023606
	Natural variant	50	1	D → N in KID syndrome and HID syndrome. dbSNP rs28931594.		VAR_015456
	Natural variant	50	1	D → Y in KID syndrome.		VAR_015935
	Natural variant	54	1	N → K in BPS. Ref.37		VAR_032750
	Natural variant	59	1	G → A in PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. Ref.35 Ref.23		VAR_009965
	Natural variant	59	1	G → S in BPS. Ref.38		VAR_032751
	Natural variant	66	1	D → H in VS and PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein.		VAR_008710
	Natural variant	71	1	I → T in deafness. Ref.34		VAR_015457
	Natural variant	75	1	R → Q in PPKDFN. Ref.15 Ref.30		VAR_015936
	Natural variant	75	1	R → W in PPKDFN and DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect.		VAR_002140
	Natural variant	77	1	W → R in DFNB1. Ref.12		VAR_002141
	Natural variant	79	1	L → P in DFNB1. Ref.2		VAR_023607
	Natural variant	80	1	Q → K in DFNB1. Ref.4		VAR_023608
	Natural variant	83	1	F → L Ref.16		VAR_002142
	Natural variant	84	1	V → L in DFNB1. Ref.14		VAR_002143
	Natural variant	86	1	T → R in deafness. Ref.34		VAR_015458
	Natural variant	90	1	L → P in DFNB1. Ref.25		VAR_015937
	Natural variant	93	1	M → I in DFNB1. Ref.4		VAR_023609
	Natural variant	95	1	V → M in DFNB1. Ref.14		VAR_002144
	Natural variant	111	1	I → T Ref.36		VAR_015938
	Natural variant	113	1	S → R in DFNB1. Ref.14		VAR_002145
	Natural variant	114	1	E → G: dbSNP rs2274083. Ref.4 Ref.9 Ref.20 Ref.34 Ref.36		VAR_009966
	Natural variant	120	1	Missing in DFNB1. Ref.4		VAR_023610
	Natural variant	123	1	T → N Ref.34		VAR_015459
	Natural variant	127	1	R → H Very common polymorphism in India. Ref.3 Ref.4 Ref.36		VAR_015939
	Natural variant	129	1	E → K in DFNB1. Ref.4		VAR_023611
	Natural variant	143	1	R → Q in DFNA3A.		VAR_015940
	Natural variant	143	1	R → W in DFNB1. Ref.2 Ref.4 Ref.18		VAR_015460
	Natural variant	153	1	V → I May contribute to deafness. Ref.3 Ref.4 Ref.36		VAR_009967
	Natural variant	159	1	D → V in DFNB1. dbSNP rs28931592. Ref.27		VAR_015941
	Natural variant	160	1	G → S: dbSNP rs34988750. Ref.3 Ref.11 Ref.16		VAR_002146
	Natural variant	165	1	R → W Ref.36		VAR_015942
	Natural variant	167	1	V → M May contribute to deafness. Ref.3		VAR_023612
	Natural variant	168	1	K → R in a patient with congenital erythrokeratodermia; unknown pathological significance.		VAR_057959
	Natural variant	169	1	C → Y		VAR_009968
	Natural variant	178	1	V → A in DFNB1. Ref.2		VAR_023613
	Natural variant	179	1	D → N in DFNA3A. dbSNP rs28931595.		VAR_032752
	Natural variant	184	1	R → P in DFNB1. Ref.4 Ref.13		VAR_015943
	Natural variant	184	1	R → Q in DFNA3A.		VAR_023614
	Natural variant	184	1	R → W in DFNB1.		VAR_009969
	Natural variant	191	1	F → L Ref.34		VAR_015461
	Natural variant	197	1	A → S in DFNA3A.		VAR_023615
	Natural variant	202	1	C → F in DFNA3A.		VAR_015944
	Natural variant	203	1	I → K in DFNB1. Ref.2		VAR_023616
	Natural variant	203	1	I → T Ref.2 Ref.20 Ref.34		VAR_009970
	Natural variant	214	1	L → P in DFNB1. Ref.2		VAR_023617
Experimental info
	Sequence conflict	86	1	T → S in AAD21314. Ref.1
	Sequence conflict	112	1	K → N in AAY25170. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P29033-1 [UniParc]. Last modified October 11, 2005. Version 3. Checksum: D35293C6747E908C	FASTA	226	26,215
	10 20 30 40 50 60 MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC 70 80 90 100 110 120 KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE 130 140 150 160 170 180 IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC 190 200 210 220 FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines." Lee S.W., Tomasetto C., Paul D., Keyomarsi K., Sager R. J. Cell Biol. 118:1213-1221(1992) [PubMed: 1324944] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana." Hamelmann C., Amedofu G.K., Albrecht K., Muntau B., Gelhaus A., Brobby G.W., Horstmann R.D. Hum. Mutat. 18:84-85(2001) [PubMed: 11439000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1 PRO-79; TRP-143; ALA-178; LYS-203 AND PRO-214, VARIANTS DFNA3A GLN-184 AND SER-197. Tissue: Blood.
[3]	"Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants." Gasmelseed N.M.A., Schmidt M., Magzoub M.M.A., Macharia M., Elmustafa O.M., Ototo B., Winkler E., Ruge G., Horstmann R.D., Meyer C.G. Hum. Mutat. 23:206-207(2004) [PubMed: 14722929] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT DFNB1 ILE-37, VARIANTS 46-ASP--GLN-48 DELINS GLU; HIS-127; ILE-153; SER-160 AND MET-167.
[4]	"GJB2 mutations: passage through Iran." Najmabadi H., Nishimura C., Kahrizi K., Riazalhosseini Y., Malekpour M., Daneshi A., Farhadi M., Mohseni M., Mahdieh N., Ebrahimi A., Bazazzadegan N., Naghavi A., Avenarius M., Arzhangi S., Smith R.J.H. Am. J. Med. Genet. A 133:132-137(2005) [PubMed: 15666300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1 HIS-32; LYS-80; ILE-93; GLU-120 DEL; LYS-129; TRP-143 AND PRO-184, VARIANTS ILE-27; GLY-114; HIS-127 AND ILE-153.
[5]	"A polymorphism in the genomic sequence of the coding region of connexin 26 in the South Indian population." Joseph A.Y., Rasool T.J. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"A novel mutation in the connexin 26 gene in the South Indian population." Joseph A.Y., Rasool T.J. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-32.
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ILE-27 AND GLY-114. Tissue: Colon.
[10]	"Connexin 26 mutations in hereditary non-syndromic sensorineural deafness." Kelsell D.P., Dunlop J., Stevens H.P., Lench N.J., Liang J.N., Parry G., Mueller R.F., Leigh I.M. Nature 387:80-83(1997) [PubMed: 9139825] [Abstract] Cited for: VARIANT THR-34.
[11]	"Connexin mutations and hearing loss." Scott D.A., Kraft M.L., Tone M.M., Sheffield V.C., Smith R.J.H. Nature 391:32-32(1998) [PubMed: 9422505] [Abstract] Cited for: SHOWS THAT VARIANT THR-34 IS NOT A CAUSE OF DEAFNESS.
[12]	"Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for genetic studies in isolated populations." Carrasquillo M.M., Zlotogora J., Barges S., Chakravarti A. Hum. Mol. Genet. 6:2163-2172(1997) [PubMed: 9328482] [Abstract] Cited for: VARIANT DFNB1 ARG-77.
[13]	"Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene." Denoyelle F., Weil D., Maw M.A., Wilcox S.A., Lench N.J., Allen-Powell D.R., Osborn A.H., Dahl H.-H.M., Middleton A., Houseman M.J., Dode C., Marlin S., Boulila-ElGaied A., Grati M., Ayadi H., BenArab S., Bitoun P., Lina-Granade G. , Godet J., Mustapha M., Loiselet J., El-Zir E., Aubois A., Joannard A., Levilliers J., Garabedian E.-N., Mueller R.F., McKinlay Gardner R.J., Petit C. Hum. Mol. Genet. 6:2173-2177(1997) [PubMed: 9336442] [Abstract] Cited for: VARIANT DFNB1 PRO-184.
[14]	"Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss." Kelley P.M., Harris D.J., Comer B.C., Askew J.W., Fowler T., Smith S.D., Kimberling W.J. Am. J. Hum. Genet. 62:792-799(1998) [PubMed: 9529365] [Abstract] Cited for: VARIANTS DFNB1 LEU-84; MET-95 AND ARG-113, VARIANTS ILE-27 AND ILE-37.
[15]	"Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma." Richard G., White T.W., Smith L.E., Bailey R.A., Compton J.G., Paul D.L., Bale S.J. Hum. Genet. 103:393-399(1998) [PubMed: 9856479] [Abstract] Cited for: VARIANT PPKDFN TRP-75.
[16]	"Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss." Scott D.A., Kraft M.L., Carmi R., Ramesh A., Elbedour K., Yairi Y., Srikumari Srisailapathy C.R., Rosengren S.S., Markham A.F., Mueller R.F., Lench N.J., van Camp G., Smith R.J.H., Sheffield V.C. Hum. Mutat. 11:387-394(1998) [PubMed: 9600457] [Abstract] Cited for: VARIANTS THR-34; LEU-83 AND SER-160.
[17]	"Connexin 26 gene linked to a dominant deafness." Denoyelle F., Lina-Granade G., Plauchu H., Bruzzone R., Chaib H., Levi-Acobas F., Weil D., Petit C. Nature 393:319-320(1998) [PubMed: 9620796] [Abstract] Cited for: VARIANT DFNA3A CYS-44.
[18]	"Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa." Brobby G.W., Muller-Myhsok B., Horstmann R.D. N. Engl. J. Med. 338:548-550(1998) [PubMed: 9471561] [Abstract] Cited for: VARIANT DFNB1 TRP-143.
[19]	"A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families." Maestrini E., Korge B.P., Ocana-Sierra J., Calzolari E., Cambiaghi S., Scudder P.M., Hovnanian A., Monaco A.P., Munro C.S. Hum. Mol. Genet. 8:1237-1243(1999) [PubMed: 10369869] [Abstract] Cited for: VARIANT VS HIS-66.
[20]	"Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population." Kudo T., Ikeda K., Kure S., Matsubara Y., Oshima T., Watanabe K., Kawase T., Narisawa K., Takasaka T. Am. J. Med. Genet. 90:141-145(2000) [PubMed: 10607953] [Abstract] Cited for: VARIANTS ILE-27; ILE-37; GLY-114 AND THR-203.
[21]	"Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family." Kelsell D.P., Wilgoss A.L., Richard G., Stevens H.P., Munro C.S., Leigh I.M. Eur. J. Hum. Genet. 8:141-144(2000) [PubMed: 10757647] [Abstract] Cited for: VARIANT PPKDFN HIS-66.
[22]	"High frequency hearing loss correlated with mutations in the GJB2 gene." Wilcox S.A., Saunders K., Osborn A.H., Arnold A., Wunderlich J., Kelly T., Collins V., Wilcox L.J., McKinlay Gardner R.J., Kamarinos M., Cone-Wesson B., Williamson R., Dahl H.-H.M. Hum. Genet. 106:399-405(2000) [PubMed: 10830906] [Abstract] Cited for: VARIANTS DFNB1 ILE-37; PRO-90 AND TRP-184.
[23]	"A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350)." Heathcote K., Syrris P., Carter N.D., Patton M.A. J. Med. Genet. 37:50-51(2000) [PubMed: 10633135] [Abstract] Cited for: VARIANT PPKDFN ALA-59.
[24]	"A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss." Morle L., Bozon M., Alloisio N., Latour P., Vandenberghe A., Plauchu H., Collet L., Edery P., Godet J., Lina-Granade G. J. Med. Genet. 37:368-370(2000) [PubMed: 10807696] [Abstract] Cited for: VARIANT DFNA3A PHE-202.
[25]	"Sensorineural hearing loss and the incidence of Cx26 mutations in Austria." Loffler J., Nekahm D., Hirst-Stadlmann A., Gunther B., Menzel H.J., Utermann G., Janecke A.R. Eur. J. Hum. Genet. 9:226-230(2001) [PubMed: 11313763] [Abstract] Cited for: VARIANT DFNB1 PRO-90, VARIANT DFNA3A GLN-143.
[26]	"Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome." Richard G., Rouan F., Willoughby C.E., Brown N., Chung P., Ryynanen M., Jabs E.W., Bale S.J., DiGiovanna J.J., Uitto J., Russell L. Am. J. Hum. Genet. 70:1341-1348(2002) [PubMed: 11912510] [Abstract] Cited for: VARIANTS KID SYNDROME ARG-12; PHE-17 AND ASN-50.
[27]	"Exploring the clinical and epidemiological complexity of GJB2-linked deafness." Gualandi F., Ravani A., Berto A., Sensi A., Trabanelli C., Falciano F., Trevisi P., Mazzoli M., Tibiletti M.G., Cristofari E., Burdo S., Ferlini A., Martini A., Calzolari E. Am. J. Med. Genet. 112:38-45(2002) [PubMed: 12239718] [Abstract] Cited for: VARIANT DFNB1 VAL-159.
[28]	"HID and KID syndromes are associated with the same connexin 26 mutation." van Geel M., van Steensel M.A.M., Kuester W., Hennies H.C., Happle R., Steijlen P.M., Koenig A. Br. J. Dermatol. 146:938-942(2002) [PubMed: 12072059] [Abstract] Cited for: VARIANT HID SYNDROME ASN-50.
[29]	"Homozygosity for the V37I Connexin 26 mutation in three unrelated children with sensorineural hearing loss." Bason L., Dudley T., Lewis K., Shah U., Potsic W., Ferraris A., Fortina P., Rappaport E., Krantz I.D. Clin. Genet. 61:459-464(2002) [PubMed: 12121355] [Abstract] Cited for: VARIANT DFNB1 ILE-37.
[30]	"The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing loss and palmoplantar keratoderma in a Turkish family." Uyguner O., Tukel T., Baykal C., Eris H., Emiroglu M., Hafiz G., Ghanbari A., Baserer N., Yuksel-Apak M., Wollnik B. Clin. Genet. 62:306-309(2002) [PubMed: 12372058] [Abstract] Cited for: VARIANT PPKDFN GLN-75.
[31]	"De novo mutation in the gene encoding connexin-26 (GJB2) in a sporadic case of keratitis-ichthyosis-deafness (KID) syndrome." Alvarez A., Del Castillo I., Pera A., Villamar M., Moreno-Pelayo M.A., Moreno F., Moreno R., Tapia M.C. Am. J. Med. Genet. A 117:89-91(2003) [PubMed: 12548749] [Abstract] Cited for: VARIANT KID SYNDROME ASN-50.
[32]	"Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome." Yotsumoto S., Hashiguchi T., Chen X., Ohtake N., Tomitaka A., Akamatsu H., Matsunaga K., Shiraishi S., Miura H., Adachi J., Kanzaki T. Br. J. Dermatol. 148:649-653(2003) [PubMed: 12752120] [Abstract] Cited for: VARIANTS KID SYNDROME ASN-50 AND TYR-50.
[33]	"A novel dominant missense mutation -- D179N -- in the GJB2 gene (connexin 26) associated with non-syndromic hearing loss." Primignani P., Castorina P., Sironi F., Curcio C., Ambrosetti U., Coviello D.A. Clin. Genet. 63:516-521(2003) [PubMed: 12786758] [Abstract] Cited for: VARIANT DFNA3A ASN-179, VARIANT DFNB1 ILE-37.
[34]	"GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation." Ohtsuka A., Yuge I., Kimura S., Namba A., Abe S., Van Laer L., Van Camp G., Usami S. Hum. Genet. 112:329-333(2003) [PubMed: 12560944] [Abstract] Cited for: VARIANTS DEAFNESS GLU-45; THR-71; ARG-86 AND TRP-143, VARIANTS ILE-27; ILE-37; GLY-114; ASN-123; LEU-191 AND THR-203.
[35]	"Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30." Marziano N.K., Casalotti S.O., Portelli A.E., Becker D.L., Forge A. Hum. Mol. Genet. 12:805-812(2003) [PubMed: 12668604] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS DFNA3A SER-44 AND TRP-75, CHARACTERIZATION OF VARIANT PPKDFN ALA-59, CHARACTERIZATION OF VARIANT VS HIS-66.
[36]	"Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India." Ramshankar M., Girirajan S., Dagan O., Ravi Shankar H.M., Jalvi R., Rangasayee R., Avraham K.B., Anand A. J. Med. Genet. 40:E68-E68(2003) [PubMed: 12746422] [Abstract] Cited for: VARIANTS ILE-27; THR-111; GLY-114; HIS-127; ILE-153 AND TRP-165.
[37]	"Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey syndrome is caused by a novel missense mutation in GJB2." Richard G., Brown N., Ishida-Yamamoto A., Krol A. J. Invest. Dermatol. 123:856-863(2004) [PubMed: 15482471] [Abstract] Cited for: VARIANT BPS LYS-54.
[38]	"G59S mutation in the GJB2 (connexin 26) gene in a patient with Bart-Pumphrey syndrome." Alexandrino F., Sartorato E.L., Marques-de-Faria A.P., Steiner C.E. Am. J. Med. Genet. A 136:282-284(2005) [PubMed: 15952212] [Abstract] Cited for: VARIANT BPS SER-59.
[39]	"Connexin mutations in Brazilian patients with skin disorders with or without hearing loss." Alexandrino F., de Oliveira C.A., Magalhaes R.F., Florence M.E., de Souza E.M., Sartorato E.L. Am. J. Med. Genet. A 149:681-684(2009) [PubMed: 19283857] [Abstract] Cited for: VARIANT ARG-168.
[40]	"Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss." Nemoto-Hasebe I., Akiyama M., Kudo S., Ishiko A., Tanaka A., Arita K., Shimizu H. Br. J. Dermatol. 0:0-0(2009) [PubMed: 19416251] [Abstract] Cited for: VARIANT ILE-27.
+	Additional computationally mapped references.

Web resources

Connexin-deafness homepage

Hereditary hearing loss homepage

Gene page

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M86849 mRNA. Translation: AAD21314.1.
AF281280 Genomic DNA. Translation: AAF91440.1.
AF479776 Genomic DNA. Translation: AAL87696.1.
AY255853 Genomic DNA. Translation: AAP34178.1.
AY275646 Genomic DNA. Translation: AAQ94940.1.
AY275647 Genomic DNA. Translation: AAQ94941.1.
AY275648 Genomic DNA. Translation: AAQ94942.1.
AY275649 Genomic DNA. Translation: AAQ94943.1.
AY275650 Genomic DNA. Translation: AAQ94944.1.
AY275651 Genomic DNA. Translation: AAQ94945.1.
AY275652 Genomic DNA. Translation: AAQ94946.1.
AY275653 Genomic DNA. Translation: AAQ94947.1.
AY275654 Genomic DNA. Translation: AAQ94948.1.
AY280971 Genomic DNA. Translation: AAQ17213.1.
AY953438 Genomic DNA. Translation: AAY25169.1.
AY953441 Genomic DNA. Translation: AAY25170.1.
BT006732 mRNA. Translation: AAP35378.1.
AL138688 Genomic DNA. Translation: CAC16959.1.
BC017048 mRNA. Translation: AAH17048.1.
BC071703 mRNA. Translation: AAH71703.1.

IPI

IPI00019868.

PIR

A43424.

RefSeq

NP_003995.2.

UniGene

Hs.524894
Hs.714494

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XIR	model	-	A	1-226	[»]
2ZW3	X-ray	3.50	A/B/C/D/E/F	1-226	[»]

ModBase

Search...

Protein family/group databases

TCDB

1.A.24.1.3. gap junction-forming connexin family.

Proteomic databases

PRIDE

P29033.

Genome annotation databases

Ensembl

ENSG00000165474. Homo sapiens. [Contig view]

GeneID

2706.

KEGG

hsa:2706.

Organism-specific databases

GeneCards

GC13M019659.

H-InvDB

HIX0011157.

HGNC

HGNC:4284. GJB2.

HPA

CAB013093.

MIM

121011. gene.
124500. phenotype.
148210. phenotype.
148350. phenotype.
149200. phenotype.
220290. phenotype.
601544. phenotype.
602540. phenotype.

Orphanet

494. Keratoderma hereditarium mutilans.
2202. Keratoderma palmoplantar - deafness.
477. KID/HID syndrome.
2698. Knuckle pods - leuconychia - sensorineural deafness.
87884. Nonsyndromic genetic deafness.

PharmGKB

PA28695.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P29033.

OMA

P29033. MYVFYIM.

Enzyme and pathway databases

Reactome

REACT_9440. Synthesis of Cx26.
REACT_9480. Gap junction trafficking and regulation.

Gene expression databases

ArrayExpress

P29033.

Bgee

P29033.

GermOnline

ENSG00000165474. Homo sapiens.

Family and domain databases

InterPro

IPR000500. Connexin.
IPR002268. Connexin26.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
IPR017991. connexins_rgn.
[Graphical view]

PANTHER

PTHR11984. Connexin. 1 hit.
PTHR11984:SF24. Connexin26. 1 hit.

Pfam

PF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]

PRINTS

PR00206. CONNEXIN.
PR01139. CONNEXINB2.

SMART

SM00037. CNX. 1 hit.
[Graphical view]

PROSITE

PS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

10698.

SOURCE

Search...

Entry information

Entry name

CXB2_HUMAN

Accession

Primary (citable) accession number: P29033
Secondary accession number(s): Q508A5 , Q508A6, Q5YLL0, Q5YLL1, Q5YLL4, Q6IPV5, Q86U88, Q96AK0, Q9H536, Q9NNY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	October 11, 2005
Last modified:	June 16, 2009
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)