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Gene Review

GJB2  -  gap junction protein, beta 2, 26kDa

Homo sapiens

Synonyms: CX26, Connexin-26, Cx26, DFNA3, DFNA3A, ...
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Disease relevance of GJB2

  • Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss [1].
  • Our data reveal striking genotype-phenotype correlations and demonstrate that dominant GJB2 mutations can disturb the gap junction system of one or several ectodermal epithelia, thereby producing multiple phenotypes: nonsyndromic SNHL, syndromic SNHL with palmoplantar keratoderma, and KID [2].
  • Cx26 was up-regulated in the carcinoma cells of 15 of the 27 invasive NST carcinomas, although the staining was usually cytoplasmic and heterogeneous [3].
  • Similarly, a lobular carcinoma did not express Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of a mucoid carcinoma [3].
  • We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal-recessive inherited non-syndromic sensorineural hearing loss (NSSHL) [4].
  • Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively) [5].

Psychiatry related information on GJB2


High impact information on GJB2


Chemical compound and disease context of GJB2


Biological context of GJB2


Anatomical context of GJB2


Associations of GJB2 with chemical compounds


Physical interactions of GJB2


Regulatory relationships of GJB2

  • CTGF mRNA and protein levels were found to be down-regulated by both Cx26 and GFP-Cx26 [32].

Other interactions of GJB2

  • Qualitative polymerase chain reaction-based allele-specific expression assays showed that expression of both GJB2 and GJB6 from the novel allele is dramatically reduced [33].
  • trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation [34].
  • In addition to the previously described sequence variant M34T in GJB2, two other sequence variants were identified: D66H also in GJB2 and R32W in GJB3 [35].
  • Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family [36].
  • Hearing impairment was caused in one family by a novel mutation in the recently identified OTOF (the DFNB9 gene), by a novel Pendred syndrome mutation (Thr193Ile) in another family, and by a GJB2 mutation (35delG also known as 30delG) in the third family [37].

Analytical, diagnostic and therapeutic context of GJB2

  • DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods [22].
  • OBJECTIVE: To compare performance after cochlear implantation in children with mutations in connexin (Cx) 26 (GJB2) or Cx30 (GJB6) and children with deafness of unknown etiology [38].
  • The high prevalence of mutations in GJB2 in some populations provides the tools for molecular diagnosis, carrier detection, and prenatal diagnosis of congenital hearing impairment [39].
  • In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population [40].
  • Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study [41].


  1. 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. (1998) [Pubmed]
  2. 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., Ryynänen, M., Jabs, E.W., Bale, S.J., DiGiovanna, J.J., Uitto, J., Russell, L. Am. J. Hum. Genet. (2002) [Pubmed]
  3. Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours. Jamieson, S., Going, J.J., D'Arcy, R., George, W.D. J. Pathol. (1998) [Pubmed]
  4. Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss. Uyguner, O., Emiroglu, M., Uzumcu, A., Hafiz, G., Ghanbari, A., Baserer, N., Yuksel-Apak, M., Wollnik, B. Clin. Genet. (2003) [Pubmed]
  5. Aberrant expression of connexin 26 is associated with lung metastasis of colorectal cancer. Ezumi, K., Yamamoto, H., Murata, K., Higashiyama, M., Damdinsuren, B., Nakamura, Y., Kyo, N., Okami, J., Ngan, C.Y., Takemasa, I., Ikeda, M., Sekimoto, M., Matsuura, N., Nojima, H., Monden, M. Clin. Cancer Res. (2008) [Pubmed]
  6. Molecular diagnosis of deafness: impact of gene identification. Usami, S., Koda, E., Tsukamoto, K., Otsuka, A., Yuge, I., Asamura, K., Abe, S., Akita, J., Namba, A. Audiol. Neurootol. (2002) [Pubmed]
  7. Cochlear implantation for children with GJB2-related deafness. Cullen, R.D., Buchman, C.A., Brown, C.J., Copeland, B.J., Zdanski, C., Pillsbury, H.C., Shores, C.G. Laryngoscope (2004) [Pubmed]
  8. GJB2 mutations and additional disabilities in a pediatric cochlear implant population. Wiley, S., Choo, D., Meinzen-Derr, J., Hilbert, L., Greinwald, J. Int. J. Pediatr. Otorhinolaryngol. (2006) [Pubmed]
  9. Using assessment of higher brain functions of children with GJB2-associated deafness and cochlear implants as a procedure to evaluate language development. Kawasaki, A., Fukushima, K., Kataoka, Y., Fukuda, S., Nishizaki, K. Int. J. Pediatr. Otorhinolaryngol. (2006) [Pubmed]
  10. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Xia, J.H., Liu, C.Y., Tang, B.S., Pan, Q., Huang, L., Dai, H.P., Zhang, B.R., Xie, W., Hu, D.X., Zheng, D., Shi, X.L., Wang, D.A., Xia, K., Yu, K.P., Liao, X.D., Feng, Y., Yang, Y.F., Xiao, J.Y., Xie, D.H., Huang, J.Z. Nat. Genet. (1998) [Pubmed]
  11. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. Morell, R.J., Kim, H.J., Hood, L.J., Goforth, L., Friderici, K., Fisher, R., Van Camp, G., Berlin, C.I., Oddoux, C., Ostrer, H., Keats, B., Friedman, T.B. N. Engl. J. Med. (1998) [Pubmed]
  12. Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa. Brobby, G.W., Müller-Myhsok, B., Horstmann, R.D. N. Engl. J. Med. (1998) [Pubmed]
  13. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Weil, D., Küssel, P., Blanchard, S., Lévy, G., Levi-Acobas, F., Drira, M., Ayadi, H., Petit, C. Nat. Genet. (1997) [Pubmed]
  14. Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss. Melchionda, S., Bicego, M., Marciano, E., Franzè, A., Morgutti, M., Bortone, G., Zelante, L., Carella, M., D'Andrea, P. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  15. Hearing genes and cisplatin deafness: a pilot study. Knoll, C., Smith, R.J., Shores, C., Blatt, J. Laryngoscope (2006) [Pubmed]
  16. Downregulation of connexin 26 in human lung cancer is related to promoter methylation. Chen, Y., Hühn, D., Knösel, T., Pacyna-Gengelbach, M., Deutschmann, N., Petersen, I. Int. J. Cancer (2005) [Pubmed]
  17. Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells. Tanaka, M., Grossman, H.B. Oncol. Rep. (2004) [Pubmed]
  18. Connexin Over-Expression Differentially Suppresses Glioma Growth and Contributes to the Bystander Effect Following HSV-Thymidine Kinase Gene Therapy. Jimenez, T., Fox, W.P., Naus, C.C., Galipeau, J., Belliveau, D.J. Cell Commun. Adhes. (2006) [Pubmed]
  19. Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients. Dalamón, V., Béhèran, A., Diamante, F., Pallares, N., Diamante, V., Elgoyhen, A.B. Hear. Res. (2005) [Pubmed]
  20. GJB2 mutations in hearing impairment: identification of a broad clinical spectrum for improved genetic counseling. Frei, K., Ramsebner, R., Lucas, T., Hamader, G., Szuhai, K., Weipoltshammer, K., Baumgartner, W.D., Wachtler, F.J., Kirschhofer, K. Laryngoscope (2005) [Pubmed]
  21. GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. Marlin, S., Feldmann, D., Blons, H., Loundon, N., Rouillon, I., Albert, S., Chauvin, P., Garabédian, E.N., Couderc, R., Odent, S., Joannard, A., Schmerber, S., Delobel, B., Leman, J., Journel, H., Catros, H., Lemarechal, C., Dollfus, H., Eliot, M.M., Delaunoy, J.L., David, A., Calais, C., Drouin-Garraud, V., Obstoy, M.F., Goizet, C., Duriez, F., Fellmann, F., Hélias, J., Vigneron, J., Montaut, B., Matin-Coignard, D., Faivre, L., Baumann, C., Lewin, P., Petit, C., Denoyelle, F. Arch. Otolaryngol. Head Neck Surg. (2005) [Pubmed]
  22. Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Pandya, A., Arnos, K.S., Xia, X.J., Welch, K.O., Blanton, S.H., Friedman, T.B., Garcia Sanchez, G., Liu MD, X.Z., Morell, R., Nance, W.E. Genet. Med. (2003) [Pubmed]
  23. Familial isolated unilateral large vestibular aqueduct syndrome. Ramírez-Camacho, R., Ramón García Berrocal, J., Arellano, B., Trinidad, A. ORL J. Otorhinolaryngol. Relat. Spec. (2003) [Pubmed]
  24. Connexin 26 expression prevents down-regulation of barrier and fence functions of tight junctions by Na+/K+-ATPase inhibitor ouabain in human airway epithelial cell line Calu-3. Go, M., Kojima, T., Takano, K., Murata, M., Koizumi, J., Kurose, M., Kamekura, R., Osanai, M., Chiba, H., Spray, D.C., Himi, T., Sawada, N. Exp. Cell Res. (2006) [Pubmed]
  25. Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12. Kelley, P.M., Abe, S., Askew, J.W., Smith, S.D., Usami, S., Kimberling, W.J. Genomics (1999) [Pubmed]
  26. Expression of the gap junction proteins connexin 26 and connexin 43 in human middle ear cholesteatoma. Choung, Y.H., Park, K., Kang, S.O., Markov Raynov, A., Ho Kim, C., Choung, P.H. Acta Otolaryngol. (2006) [Pubmed]
  27. Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. Elvira, M., Díez, J.A., Wang, K.K., Villalobo, A. J. Biol. Chem. (1993) [Pubmed]
  28. Co-ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy. Saito, T., Oyamada, M., Yamasaki, H., Mori, M., Kudo, R. Int. J. Cancer (1997) [Pubmed]
  29. Expression of gap junction connexins in the human endometrium throughout the menstrual cycle. Jahn, E., Classen-Linke, I., Kusche, M., Beier, H.M., Traub, O., Grümmer, R., Winterhager, E. Hum. Reprod. (1995) [Pubmed]
  30. Aberrant expression pattern of gap junction connexins in endometriotic tissues. Regidor, P.A., Regidor, M., Schindler, A.E., Winterhager, E. Mol. Hum. Reprod. (1997) [Pubmed]
  31. The cochlear F-box protein OCP1 associates with OCP2 and connexin 26. Henzl, M.T., Thalmann, I., Larson, J.D., Ignatova, E.G., Thalmann, R. Hear. Res. (2004) [Pubmed]
  32. Connexin26 regulates the expression of angiogenesis-related genes in human breast tumor cells by both GJIC-dependent and -independent mechanisms. Qin, H., Shao, Q., Thomas, T., Kalra, J., Alaoui-Jamali, M.A., Laird, D.W. Cell Commun. Adhes. (2003) [Pubmed]
  33. Expression of GJB2 and GJB6 is reduced in a novel DFNB1 allele. Wilch, E., Zhu, M., Burkhart, K.B., Regier, M., Elfenbein, J.L., Fisher, R.A., Friderici, K.H. Am. J. Hum. Genet. (2006) [Pubmed]
  34. trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. Rouan, F., White, T.W., Brown, N., Taylor, A.M., Lucke, T.W., Paul, D.L., Munro, C.S., Uitto, J., Hodgins, M.B., Richard, G. J. Cell. Sci. (2001) [Pubmed]
  35. 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. (2000) [Pubmed]
  36. Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family. de Brouwer, A.P., Pennings, R.J., Roeters, M., Van Hauwe, P., Astuto, L.M., Hoefsloot, L.H., Huygen, P.L., van den Helm, B., Deutman, A.F., Bork, J.M., Kimberling, W.J., Cremers, F.P., Cremers, C.W., Kremer, H. Hum. Genet. (2003) [Pubmed]
  37. Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus. Adato, A., Raskin, L., Petit, C., Bonne-Tamir, B. Eur. J. Hum. Genet. (2000) [Pubmed]
  38. Connexin-associated deafness and speech perception outcome of cochlear implantation. Taitelbaum-Swead, R., Brownstein, Z., Muchnik, C., Kishon-Rabin, L., Kronenberg, J., Megirov, L., Frydman, M., Hildesheimer, M., Avraham, K.B. Arch. Otolaryngol. Head Neck Surg. (2006) [Pubmed]
  39. Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins. Rabionet, R., Gasparini, P., Estivill, X. Hum. Mutat. (2000) [Pubmed]
  40. Molecular epidemiology of DFNB1 deafness in France. Roux, A.F., Pallares-Ruiz, N., Vielle, A., Faugère, V., Templin, C., Leprevost, D., Artières, F., Lina, G., Molinari, N., Blanchet, P., Mondain, M., Claustres, M. BMC Med. Genet. (2004) [Pubmed]
  41. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Del Castillo, I., Moreno-Pelayo, M.A., Del Castillo, F.J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D.J., Pandya, A., Siemering, K.R., Chamberlin, G.P., Ballana, E., Wuyts, W., Maciel-Guerra, A.T., Alvarez, A., Villamar, M., Shohat, M., Abeliovich, D., Dahl, H.H., Estivill, X., Gasparini, P., Hutchin, T., Nance, W.E., Sartorato, E.L., Smith, R.J., Van Camp, G., Avraham, K.B., Petit, C., Moreno, F. Am. J. Hum. Genet. (2003) [Pubmed]
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