P29033 (CXB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	226 AA.
Sequence status	Complete.
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. Interacts with CNST By similarity. Ref.11
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Involvement in disease	Deafness, autosomal recessive, 1A (DFNB1A) [MIM:220290]: A form of non-syndromic 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Ref.4 Ref.10 Ref.14 Ref.15 Ref.16 Ref.20 Ref.24 Ref.27 Ref.29 Ref.31 Ref.35 Ref.43 Ref.46 Ref.50 Deafness, autosomal dominant, 3A (DFNA3A) [MIM:601544]: A form of non-syndromic 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.19 Ref.26 Ref.27 Ref.35 Ref.37 Ref.50 Vohwinkel syndrome (VS) [MIM:124500]: VS is an autosomal dominant disease characterized by hyperkeratosis, constriction on fingers and toes and congenital deafness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.37 Keratoderma, palmoplantar, with deafness (PPKDFN) [MIM:148350]: An autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.23 Ref.25 Ref.32 Ref.37 Ref.42 Ref.47 Keratitis-ichthyosis-deafness syndrome (KID syndrome) [MIM:148210]: An autosomal dominant form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Keratitis-ichthyosis-deafness 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Bart-Pumphrey syndrome (BPS) [MIM:149200]: An autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.41 Ichthyosis hystrix-like with deafness syndrome (HID syndrome) [MIM:602540]: An autosomal dominant 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. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the connexin family. Beta-type (group I) subfamily.
Caution	The Thr-34 allele was originally thought to be a cause of autosomal dominant and recessive deafness (DFNA3 and DFNB1) (Ref.12). However, Thr-34 effect on hearing is controversial. Some studies supports its pathogenic role (Ref.45 and Ref.44). Others provide evidence of the non-pathogenic nature of this variant (Ref.13 and Ref.39).

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 Transmembrane helix
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement Ref.1. Source: ProtInc cellular membrane organization Traceable author statement. Source: Reactome gap junction assembly Traceable author statement. Source: Reactome male genitalia development Inferred from electronic annotation. Source: Compara sensory perception of sound Traceable author statement Ref.12PubMed 9482292. Source: ProtInc transport Traceable author statement Ref.1. Source: ProtInc
Cellular_component	connexon complex Traceable author statement Ref.1. Source: ProtInc endoplasmic reticulum-Golgi intermediate compartment Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lateral plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	gap junction channel activity Inferred from electronic annotation. Source: Compara
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

Helical; Potential

Topological domain

41 – 75

35

Extracellular Potential

Transmembrane

76 – 98

23

Helical; Potential

Topological domain

99 – 131

33

Cytoplasmic Potential

Transmembrane

132 – 154

23

Helical; Potential

Topological domain

155 – 192

38

Extracellular Potential

Transmembrane

193 – 215

23

Helical; Potential

Topological domain

216 – 226

11

Cytoplasmic Potential

Amino acid modifications

Disulfide bond

53 ↔ 180

Ref.11

Disulfide bond

60 ↔ 174

Ref.11

Disulfide bond

64 ↔ 169

Ref.11

Natural variations

Natural variant

12

1

G → R in KID syndrome. Ref.28

VAR_015453

Natural variant

17

1

S → F in KID syndrome. Ref.28
Corresponds to variant rs28929485 [ dbSNP | Ensembl ].

VAR_015454

Natural variant

27

1

V → I. Ref.4 Ref.9 Ref.16 Ref.22 Ref.36 Ref.38 Ref.49
Corresponds to variant rs2274084 [ dbSNP | Ensembl ].

VAR_002137

Natural variant

32

1

R → H in DFNB1A. Ref.4

VAR_023605

Natural variant

32

1

R → L. Ref.6

VAR_016839

Natural variant

34

1

M → T Frequently found in deafness patients; it is correctly synthesized and targeted to the plasma membrane; it inefficiently forms intercellular channels that display an abnormal electrical behavior; uncertain pathological significance. Ref.12 Ref.13 Ref.18 Ref.39 Ref.44 Ref.45
Corresponds to variant rs35887622 [ dbSNP | Ensembl ].

VAR_002138

Natural variant

37

1

V → I in DFNB1A; was reported first as a polymorphism. Ref.3 Ref.16 Ref.22 Ref.24 Ref.31 Ref.35 Ref.36 Ref.45

VAR_002139

Natural variant

44

1

W → C in DFNA3A. Ref.19

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. Ref.37

VAR_032749

Natural variant

45

1

G → E in deafness. Ref.36

VAR_015455

Natural variant

46 – 48

3

DEQ → E May contribute to deafness. Ref.50

VAR_023606

Natural variant

46

1

D → E in DFNA3A; the mutant is targeted to the plasma membrane but failes to transfer ionic calcium or propidium iodide intercellularly suggesting disruption of both ionic and biochemical coupling; heterozygous gap junctions also show dysfunctional intercellular couplings and hemichannel opening confirming the dominant-negative nature of the mutation. Ref.50

VAR_060798

Natural variant

50

1

D → N in KID syndrome and HID syndrome. Ref.28 Ref.30 Ref.33 Ref.34
Corresponds to variant rs28931594 [ dbSNP | Ensembl ].

VAR_015456

Natural variant

50

1

D → Y in KID syndrome. Ref.34

VAR_015935

Natural variant

54

1

N → K in BPS. Ref.40

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.25 Ref.37

VAR_009965

Natural variant

59

1

G → S in BPS. Ref.41

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. Ref.21 Ref.23 Ref.37

VAR_008710

Natural variant

71

1

I → T in deafness. Ref.36

VAR_015457

Natural variant

73

1

H → R in PPKDFN; the mutant has a dominant-negative effect on connexin trafficking. Ref.47

VAR_060799

Natural variant

75

1

R → Q in PPKDFN; the mutant protein completely prevents the formation of functional channels. Ref.32 Ref.42

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. Ref.17 Ref.37

VAR_002140

Natural variant

77

1

W → R in DFNB1A. Ref.14

VAR_002141

Natural variant

79

1

L → P in DFNB1A. Ref.2

VAR_023607

Natural variant

80

1

Q → K in DFNB1A. Ref.4

VAR_023608

Natural variant

83

1

F → L. Ref.18

VAR_002142

Natural variant

84

1

V → L in DFNB1A; sorted to the plasma membrane normally and forms gap junctions that were morphologically and electrically indistinguishable from those of control; the mutation reduces the permeability of GJB2 gap junction channels to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), resulting in blockade of the Ins(1,4,5)P3-induced inward calcium current in neighboring cells. Ref.16 Ref.43

VAR_002143

Natural variant

84

1

V → M in DFNB1A; the mutant disrupts cellular communication. Ref.46

VAR_060800

Natural variant

86

1

T → R in DFNB1A; does not form gap junctions since the mutated protein is confined in the cytoplasm and not transported to the cell membrane; when the mutation is coexpressed with the wild-type protein ionic and biochemical coupling is normal consistent with the recessive nature of the mutation. Ref.36 Ref.50

VAR_015458

Natural variant

90

1

L → P in DFNB1A. Ref.24 Ref.27

VAR_015937

Natural variant

93

1

M → I in DFNB1A. Ref.4

VAR_023609

Natural variant

95

1

V → M in DFNB1A. Ref.16

VAR_002144

Natural variant

111

1

I → T. Ref.38

VAR_015938

Natural variant

113

1

S → R in DFNB1A. Ref.16

VAR_002145

Natural variant

114

1

E → G. Ref.4 Ref.9 Ref.22 Ref.36 Ref.38
Corresponds to variant rs2274083 [ dbSNP | Ensembl ].

VAR_009966

Natural variant

118

1

Missing in DFNB1A.

VAR_060801

Natural variant

120

1

Missing in DFNB1A. Ref.4

VAR_023610

Natural variant

123

1

T → N. Ref.36

VAR_015459

Natural variant

127

1

R → H Very common polymorphism in India. Ref.3 Ref.4 Ref.38

VAR_015939

Natural variant

129

1

E → K in DFNB1A. Ref.4

VAR_023611

Natural variant

143

1

R → Q in DFNA3A. Ref.27

VAR_015940

Natural variant

143

1

R → W in DFNB1A. Ref.2 Ref.4 Ref.20 Ref.36

VAR_015460

Natural variant

153

1

V → I May contribute to deafness. Ref.3 Ref.4 Ref.38

VAR_009967

Natural variant

159

1

D → V in DFNB1A. Ref.29
Corresponds to variant rs28931592 [ dbSNP | Ensembl ].

VAR_015941

Natural variant

160

1

G → S. Ref.3 Ref.18
Corresponds to variant rs34988750 [ dbSNP | Ensembl ].

VAR_002146

Natural variant

165

1

R → W. Ref.38

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. Ref.48

VAR_057959

Natural variant

169

1

C → Y.

VAR_009968

Natural variant

178

1

V → A in DFNB1A. Ref.2

VAR_023613

Natural variant

179

1

D → N in DFNA3A. Ref.35
Corresponds to variant rs28931595 [ dbSNP | Ensembl ].

VAR_032752

Natural variant

184

1

R → P in DFNB1A. Ref.4 Ref.15

VAR_015943

Natural variant

184

1

R → Q in DFNA3A. Ref.2

VAR_023614

Natural variant

184

1

R → W in DFNB1A. Ref.24

VAR_009969

Natural variant

191

1

F → L. Ref.36

VAR_015461

Natural variant

197

1

A → S in DFNA3A. Ref.2

VAR_023615

Natural variant

202

1

C → F in DFNA3A. Ref.26

VAR_015944

Natural variant

203

1

I → K in DFNB1A. Ref.2

VAR_023616

Natural variant

203

1

I → T. Ref.22 Ref.36

VAR_009970

Natural variant

214

1

L → P in DFNB1A. 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

Secondary structure

1

.

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226

Helix Strand Turn

Details...

Helix

5 – 11

7

Helix

22 – 43

22

Helix

46 – 49

4

Beta strand

52 – 54

3

Helix

60 – 66

7

Helix

73 – 83

11

Helix

85 – 105

21

Turn

106 – 108

3

Turn

126 – 130

5

Helix

131 – 156

26

Turn

157 – 159

3

Beta strand

160 – 162

3

Beta strand

165 – 169

5

Beta strand

174 – 181

8

Helix

185 – 215

31

Sequences

	Sequence		Length	Mass (Da)
	P29033 [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1A 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT DFNB1A 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DFNB1A 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ILE-27 AND GLY-114. Tissue: Colon.
[10]	"A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment." del Castillo F.J., Rodriguez-Ballesteros M., Alvarez A., Hutchin T., Leonardi E., de Oliveira C.A., Azaiez H., Brownstein Z., Avenarius M.R., Marlin S., Pandya A., Shahin H., Siemering K.R., Weil D., Wuyts W., Aguirre L.A., Martin Y., Moreno-Pelayo M.A. , Villamar M., Avraham K.B., Dahl H.H., Kanaan M., Nance W.E., Petit C., Smith R.J., Van Camp G., Sartorato E.L., Murgia A., Moreno F., del Castillo I. J. Med. Genet. 42:588-594(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DFNB1A.
[11]	"Structure of the connexin 26 gap junction channel at 3.5 A resolution." Maeda S., Nakagawa S., Suga M., Yamashita E., Oshima A., Fujiyoshi Y., Tsukihara T. Nature 458:597-602(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS), SUBUNIT, DISULFIDE BONDS.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANT THR-34.
[13]	"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] [Europe PMC] [Abstract] Cited for: SHOWS THAT VARIANT THR-34 IS NOT A CAUSE OF DEAFNESS.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A ARG-77.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS DFNB1A GLU-118 DEL AND PRO-184.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS DFNB1A LEU-84; MET-95 AND ARG-113, VARIANTS ILE-27 AND ILE-37.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN TRP-75.
[18]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS THR-34; LEU-83 AND SER-160.
[19]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNA3A CYS-44.
[20]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A TRP-143.
[21]	"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] [Europe PMC] [Abstract] Cited for: VARIANT VS HIS-66.
[22]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-27; ILE-37; GLY-114 AND THR-203.
[23]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN HIS-66.
[24]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS DFNB1A ILE-37; PRO-90 AND TRP-184.
[25]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN ALA-59.
[26]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNA3A PHE-202.
[27]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A PRO-90, VARIANT DFNA3A GLN-143.
[28]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS KID SYNDROME ARG-12; PHE-17 AND ASN-50.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A VAL-159.
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANT HID SYNDROME ASN-50.
[31]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A ILE-37.
[32]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN GLN-75.
[33]	"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] [Europe PMC] [Abstract] Cited for: VARIANT KID SYNDROME ASN-50.
[34]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS KID SYNDROME ASN-50 AND TYR-50.
[35]	"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] [Europe PMC] [Abstract] Cited for: VARIANT DFNA3A ASN-179, VARIANT DFNB1A ILE-37.
[36]	"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] [Europe PMC] [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.
[37]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS DFNA3A SER-44 AND TRP-75, CHARACTERIZATION OF VARIANT PPKDFN ALA-59, CHARACTERIZATION OF VARIANT VS HIS-66.
[38]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-27; THR-111; GLY-114; HIS-127; ILE-153 AND TRP-165.
[39]	"Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene." Feldmann D., Denoyelle F., Loundon N., Weil D., Garabedian E.N., Couderc R., Joannard A., Schmerber S., Delobel B., Leman J., Journel H., Catros H., Ferrec C., Drouin-Garraud V., Obstoy M.F., Moati L., Petit C., Marlin S. Eur. J. Hum. Genet. 12:279-284(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NON-PATHOGENIC ROLE OF VARIANT THR-34.
[40]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BPS LYS-54.
[41]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BPS SER-59.
[42]	"Functional analysis of R75Q mutation in the gene coding for Connexin 26 identified in a family with nonsyndromic hearing loss." Piazza V., Beltramello M., Menniti M., Colao E., Malatesta P., Argento R., Chiarella G., Gallo L.V., Catalano M., Perrotti N., Mammano F., Cassandro E. Clin. Genet. 68:161-166(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN GLN-75, CHARACTERIZATION OF VARIANT PPKDFN GLN-75.
[43]	"Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies recessive hereditary deafness." Beltramello M., Piazza V., Bukauskas F.F., Pozzan T., Mammano F. Nat. Cell Biol. 7:63-69(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT DFNB1A LEU-84.
[44]	"Pathogenetic role of the deafness-related M34T mutation of Cx26." Bicego M., Beltramello M., Melchionda S., Carella M., Piazza V., Zelante L., Bukauskas F.F., Arslan E., Cama E., Pantano S., Bruzzone R., D'Andrea P., Mammano F. Hum. Mol. Genet. 15:2569-2587(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT THR-34, PATHOGENIC ROLE OF VARIANT THR-34.
[45]	"M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance." Pollak A., Skorka A., Mueller-Malesinska M., Kostrzewa G., Kisiel B., Waligora J., Krajewski P., Oldak M., Korniszewski L., Skarzynski H., Ploski R. Am. J. Med. Genet. A 143:2534-2543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE PATHOGENICITY OF VARIANTS THR-34 AND ILE-37.
[46]	"A novel hearing-loss-related mutation occurring in the GJB2 basal promoter." Matos T.D., Caria H., Simoes-Teixeira H., Aasen T., Nickel R., Jagger D.J., O'Neill A., Kelsell D.P., Fialho G. J. Med. Genet. 44:721-725(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNB1A MET-84, CHARACTERIZATION OF VARIANT DFNB1A MET-84.
[47]	"A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness." de Zwart-Storm E.A., Hamm H., Stoevesandt J., Steijlen P.M., Martin P.E., van Geel M., van Steensel M.A.M. J. Med. Genet. 45:161-166(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PPKDFN ARG-73, CHARACTERIZATION OF VARIANT PPKDFN ARG-73.
[48]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ARG-168.
[49]	"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. 161:452-455(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-27.
[50]	"Different functional consequences of two missense mutations in the GJB2 gene associated with non-syndromic hearing loss." Choi S.-Y., Park H.-J., Lee K.Y., Dinh E.H., Chang Q., Ahmad S., Lee S.H., Bok J., Lin X., Kim U.-K. Hum. Mutat. 30:E716-E727(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNA3A GLU-46, VARIANT DFNB1A ARG-86, CHARACTERIZATION OF VARIANT DFNA3A GLU-46, CHARACTERIZATION OF VARIANT DFNB1A ARG-86.
+	Additional computationally mapped references.

Web resources

Connexin-deafness homepage

Hereditary hearing loss homepage

Gene page

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_004004.5.

UniGene

Hs.524894.
Hs.714494.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3IZ1	electron microscopy	-	A/B/C	1-226	[»]
3IZ2	electron microscopy	-	A/B/C	8-226	[»]

ProteinModelPortal

P29033.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59742N.

IntAct

P29033. 1 interaction.

Protein family/group databases

TCDB

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

PTM databases

PhosphoSite

P29033.

Polymorphism databases

DMDM

77416855.

Proteomic databases

PaxDb

P29033.

PRIDE

P29033.

Protocols and materials databases

DNASU

2706.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000382844; ENSP00000372295; ENSG00000165474.
ENST00000382848; ENSP00000372299; ENSG00000165474.

GeneID

2706.

KEGG

hsa:2706.

UCSC

uc001umy.3. human.

Organism-specific databases

CTD

2706.

GeneCards

GC13M020761.

HGNC

HGNC:4284. GJB2.

HPA

CAB013093.

MIM

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

neXtProt

NX_P29033.

Orphanet

90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
494. Keratoderma hereditarium mutilans.
477. KID syndrome.
2698. Knuckle pads - leuconychia - sensorineural deafness.
2202. Palmoplantar keratoderma - deafness.

PharmGKB

PA28695.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39645.

HOVERGEN

HBG009576.

InParanoid

P29033.

KO

K07621.

OMA

MDWSTLQ.

OrthoDB

EOG4PK28F.

PhylomeDB

P29033.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

P29033.

Bgee

P29033.

Genevestigator

P29033.

GermOnline

ENSG00000165474. Homo sapiens.

Family and domain databases

InterPro

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

PANTHER

PTHR11984. PTHR11984. 1 hit.
PTHR11984:SF24. PTHR11984:SF24. 1 hit.

Pfam

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

PRINTS

PR00206. CONNEXIN.
PR01139. CONNEXINB2.

SMART

SM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P29033.

GenomeRNAi

2706.

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:	May 1, 2013
This is version 152 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.