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P29033 (CXB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gap junction beta-2 protein
Alternative name(s):
Connexin-26
Short name=Cx26
Gene names
Name:GJB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length226 AA.
Sequence statusComplete.
Protein existenceEvidence 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 junctiongap 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.44 Ref.47 Ref.48 Ref.53 Ref.54

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.53

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 Ref.43 Ref.51

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.49

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, photophobia, 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.46 and Ref.45). Others provide evidence of the non-pathogenic nature of this variant (Ref.13 and Ref.39).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 226226Gap junction beta-2 protein
PRO_0000057855

Regions

Topological domain1 – 2020Cytoplasmic Potential
Transmembrane21 – 4020Helical; Potential
Topological domain41 – 7535Extracellular Potential
Transmembrane76 – 9823Helical; Potential
Topological domain99 – 13133Cytoplasmic Potential
Transmembrane132 – 15423Helical; Potential
Topological domain155 – 19238Extracellular Potential
Transmembrane193 – 21523Helical; Potential
Topological domain216 – 22611Cytoplasmic Potential

Amino acid modifications

Disulfide bond53 ↔ 180 Ref.11
Disulfide bond60 ↔ 174 Ref.11
Disulfide bond64 ↔ 169 Ref.11

Natural variations

Natural variant121G → R in KID syndrome. Ref.28
VAR_015453
Natural variant171S → F in KID syndrome. Ref.28
Corresponds to variant rs28929485 [ dbSNP | Ensembl ].
VAR_015454
Natural variant271V → I. Ref.4 Ref.9 Ref.16 Ref.22 Ref.36 Ref.38 Ref.52
Corresponds to variant rs2274084 [ dbSNP | Ensembl ].
VAR_002137
Natural variant321R → H in DFNB1A. Ref.4
VAR_023605
Natural variant321R → L. Ref.6
VAR_016839
Natural variant341M → 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.45 Ref.46
Corresponds to variant rs35887622 [ dbSNP | Ensembl ].
VAR_002138
Natural variant371V → I in DFNB1A; was reported first as a polymorphism. Ref.3 Ref.16 Ref.22 Ref.24 Ref.31 Ref.35 Ref.36 Ref.46 Ref.54
Corresponds to variant rs72474224 [ dbSNP | Ensembl ].
VAR_002139
Natural variant441W → C in DFNA3A. Ref.19
VAR_008709
Natural variant441W → S in DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. Ref.37
VAR_032749
Natural variant451G → E in deafness. Ref.36
VAR_015455
Natural variant46 – 483DEQ → E May contribute to deafness. Ref.53
VAR_023606
Natural variant461D → 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.53
VAR_060798
Natural variant501D → N in KID syndrome and HID syndrome. Ref.28 Ref.30 Ref.33 Ref.34
Corresponds to variant rs28931594 [ dbSNP | Ensembl ].
VAR_015456
Natural variant501D → Y in KID syndrome. Ref.34
VAR_015935
Natural variant541N → K in BPS. Ref.40
VAR_032750
Natural variant591G → 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 variant591G → S in BPS. Ref.41
VAR_032751
Natural variant661D → 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 variant711I → T in deafness. Ref.36
VAR_015457
Natural variant731H → R in PPKDFN; the mutant has a dominant-negative effect on connexin trafficking. Ref.49
VAR_060799
Natural variant751R → Q in PPKDFN; the mutant protein completely prevents the formation of functional channels. Ref.32 Ref.42
VAR_015936
Natural variant751R → 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 variant771W → R in DFNB1A. Ref.14
VAR_002141
Natural variant791L → P in DFNB1A. Ref.2
VAR_023607
Natural variant801Q → K in DFNB1A. Ref.4
VAR_023608
Natural variant831F → L. Ref.18
Corresponds to variant rs111033218 [ dbSNP | Ensembl ].
VAR_002142
Natural variant841V → 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.44
VAR_002143
Natural variant841V → M in DFNB1A; the mutant disrupts cellular communication. Ref.48
VAR_060800
Natural variant861T → 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.53
VAR_015458
Natural variant901L → P in DFNB1A. Ref.24 Ref.27
VAR_015937
Natural variant931M → I in DFNB1A. Ref.4
VAR_023609
Natural variant951V → M in DFNB1A. Ref.16
VAR_002144
Natural variant1111I → T. Ref.38
VAR_015938
Natural variant1131S → R in DFNB1A. Ref.16
VAR_002145
Natural variant1141E → G. Ref.4 Ref.9 Ref.22 Ref.36 Ref.38
Corresponds to variant rs2274083 [ dbSNP | Ensembl ].
VAR_009966
Natural variant1171D → H. Ref.43
VAR_069519
Natural variant1181Missing in DFNB1A.
VAR_060801
Natural variant1201Missing in DFNB1A. Ref.4
VAR_023610
Natural variant1231T → N. Ref.36
Corresponds to variant rs111033188 [ dbSNP | Ensembl ].
VAR_015459
Natural variant1271R → H Very common polymorphism in India. Ref.3 Ref.4 Ref.38
Corresponds to variant rs111033196 [ dbSNP | Ensembl ].
VAR_015939
Natural variant1291E → K in DFNB1A. Ref.4
VAR_023611
Natural variant1301G → A in DFNB1A. Ref.54
VAR_069520
Natural variant1301G → D in DFNB1A. Ref.47
VAR_069521
Natural variant1301G → V in VS. Ref.43 Ref.51
VAR_069522
Natural variant1421Missing. Ref.43
VAR_069523
Natural variant1431R → Q in DFNA3A. Ref.27
VAR_015940
Natural variant1431R → W in DFNB1A. Ref.2 Ref.4 Ref.20 Ref.36
VAR_015460
Natural variant1481A → P. Ref.43
VAR_069524
Natural variant1531V → I May contribute to deafness. Ref.3 Ref.4 Ref.38
Corresponds to variant rs111033186 [ dbSNP | Ensembl ].
VAR_009967
Natural variant1591D → V in DFNB1A. Ref.29
Corresponds to variant rs28931592 [ dbSNP | Ensembl ].
VAR_015941
Natural variant1601G → S. Ref.3 Ref.18
Corresponds to variant rs34988750 [ dbSNP | Ensembl ].
VAR_002146
Natural variant1651R → W. Ref.38
VAR_015942
Natural variant1671V → M May contribute to deafness. Ref.3
VAR_023612
Natural variant1681K → R in a patient with congenital erythrokeratodermia; unknown pathological significance. Ref.50
Corresponds to variant rs200104362 [ dbSNP | Ensembl ].
VAR_057959
Natural variant1691C → Y.
VAR_009968
Natural variant1781V → A in DFNB1A. Ref.2
VAR_023613
Natural variant1791D → N in DFNA3A. Ref.35
Corresponds to variant rs28931595 [ dbSNP | Ensembl ].
VAR_032752
Natural variant1841R → P in DFNB1A. Ref.4 Ref.15
VAR_015943
Natural variant1841R → Q in DFNA3A. Ref.2
VAR_023614
Natural variant1841R → W in DFNB1A. Ref.24
VAR_009969
Natural variant1911F → L. Ref.36
VAR_015461
Natural variant1971A → S in DFNA3A. Ref.2
VAR_023615
Natural variant2021C → F in DFNA3A. Ref.26
VAR_015944
Natural variant2031I → K in DFNB1A. Ref.2
VAR_023616
Natural variant2031I → T. Ref.22 Ref.36
Corresponds to variant rs76838169 [ dbSNP | Ensembl ].
VAR_009970
Natural variant2141L → P in DFNB1A. Ref.2
VAR_023617

Experimental info

Sequence conflict861T → S in AAD21314. Ref.1
Sequence conflict1121K → N in AAY25170. Ref.4

Secondary structure

........................... 226
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P29033 [UniParc].

Last modified October 11, 2005. Version 3.
Checksum: D35293C6747E908C

FASTA22626,215
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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]"Mutation analysis of the GJB2 (connexin 26) gene in Egypt."
Snoeckx R.L., Hassan D.M., Kamal N.M., Van Den Bogaert K., Van Camp G.
Hum. Mutat. 26:60-61(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VS VAL-130, VARIANTS HIS-117; PHE-142 DEL AND PRO-148.
[44]"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.
[45]"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.
[46]"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.
[47]"A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort."
Putcha G.V., Bejjani B.A., Bleoo S., Booker J.K., Carey J.C., Carson N., Das S., Dempsey M.A., Gastier-Foster J.M., Greinwald J.H. Jr., Hoffmann M.L., Jeng L.J., Kenna M.A., Khababa I., Lilley M., Mao R., Muralidharan K., Otani I.M. expand/collapse author list , Rehm H.L., Schaefer F., Seltzer W.K., Spector E.B., Springer M.A., Weck K.E., Wenstrup R.J., Withrow S., Wu B.L., Zariwala M.A., Schrijver I.
Genet. Med. 9:413-426(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNB1A ASP-130.
[48]"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.
[49]"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.
[50]"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.
[51]"New evidence for the correlation of the p.G130V mutation in the GJB2 gene and syndromic hearing loss with palmoplantar keratoderma."
Iossa S., Chinetti V., Auletta G., Laria C., De Luca M., Rienzo M., Giannini P., Delfino M., Ciccodicola A., Marciano E., Franze A.
Am. J. Med. Genet. A 149:685-688(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VS VAL-130.
[52]"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.
[53]"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.
[54]"Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss."
Riahi Z., Hammami H., Ouragini H., Messai H., Zainine R., Bouyacoub Y., Romdhane L., Essaid D., Kefi R., Rhimi M., Bedoui M., Dhaouadi A., Feldmann D., Jonard L., Besbes G., Abdelhak S.
Gene 525:1-4(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DFNB1A ILE-37 AND ALA-130.
+Additional computationally mapped references.

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.
PIRA43424.
RefSeqNP_003995.2. NM_004004.5.
XP_005266411.1. XM_005266354.1.
XP_005266412.1. XM_005266355.1.
XP_005266413.1. XM_005266356.1.
UniGeneHs.524894.
Hs.714494.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XIRmodel-A1-226[»]
2ZW3X-ray3.50A/B/C/D/E/F1-226[»]
3IZ1electron microscopy-A/B/C1-226[»]
3IZ2electron microscopy-A/B/C8-226[»]
ProteinModelPortalP29033.
SMRP29033. Positions 2-217.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108972. 6 interactions.
DIPDIP-59742N.
IntActP29033. 1 interaction.

Chemistry

GuidetoPHARMACOLOGY716.

Protein family/group databases

TCDB1.A.24.1.3. the gap junction-forming connexin (connexin) family.

PTM databases

PhosphoSiteP29033.

Polymorphism databases

DMDM77416855.

Proteomic databases

PaxDbP29033.
PRIDEP29033.

Protocols and materials databases

DNASU2706.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382844; ENSP00000372295; ENSG00000165474.
ENST00000382848; ENSP00000372299; ENSG00000165474.
GeneID2706.
KEGGhsa:2706.
UCSCuc001umy.3. human.

Organism-specific databases

CTD2706.
GeneCardsGC13M020761.
HGNCHGNC:4284. GJB2.
HPACAB013093.
MIM121011. gene.
124500. phenotype.
148210. phenotype.
148350. phenotype.
149200. phenotype.
220290. phenotype.
601544. phenotype.
602540. phenotype.
neXtProtNX_P29033.
Orphanet90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
330029. Hypotrichosis-deafness syndrome.
494. Keratoderma hereditarium mutilans.
477. KID syndrome.
2698. Knuckle pads-leuconychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome.
2202. Palmoplantar keratoderma-deafness syndrome.
166286. Porokeratotic eccrine ostial and dermal duct nevus.
PharmGKBPA28695.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39645.
HOVERGENHBG009576.
InParanoidP29033.
KOK07621.
OMAMYVFYIM.
OrthoDBEOG7P2XSS.
PhylomeDBP29033.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpressP29033.
BgeeP29033.
GenevestigatorP29033.

Family and domain databases

InterProIPR000500. Connexin.
IPR002268. Connexin26.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PTHR11984:SF24. PTHR11984:SF24. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
PR01139. CONNEXINB2.
SMARTSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP29033.
GeneWikiGJB2.
GenomeRNAi2706.
NextBio10698.
PROP29033.
SOURCESearch...

Entry information

Entry nameCXB2_HUMAN
AccessionPrimary (citable) accession number: P29033
Secondary accession number(s): Q508A5 expand/collapse secondary AC list , 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: April 16, 2014
This is version 163 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM