Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1 (also known as connexin 26 deafness or GJB2-related deafness).[5] One fairly common mutation is the deletion of one guanine from a string of six, resulting in a frameshift and termination of the protein at amino acid number 13. Having two copies of this mutation results in deafness.[6]
Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle.[7] The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer,[8] breast cancer,[9] and bladder cancer.[10] Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion[11] and by stimulating the self-perpetuation ability of cancer stem cells.[12]
Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels. Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are designated by their molecular mass. Another system of nomenclature divides gap junction proteins into two categories, alpha and beta, according to sequence similarities at the nucleotide and amino acid levels. For example, CX43 (GJA1) is designated alpha-1 gap junction protein, whereas GJB1 (CX32), and GJB2 (CX26; this protein) are called beta-1 and beta-2 gap junction proteins, respectively. This nomenclature emphasizes that GJB1 and GJB2 are more homologous to each other than either of them is to gap junction protein, alpha GJA1.[13]
Thalmann R, Henzl MT, Killick R, Ignatova EG, Thalmann I (January 2003). "Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2". Acta Oto-Laryngologica. 123 (2): 203–8. doi:10.1080/0036554021000028100. PMID12701741. S2CID2048758.
Yotsumoto S, Hashiguchi T, Chen X, Ohtake N, Tomitaka A, Akamatsu H, Matsunaga K, Shiraishi S, Miura H, Adachi J, Kanzaki T (April 2003). "Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome". The British Journal of Dermatology. 148 (4): 649–53. doi:10.1046/j.1365-2133.2003.05245.x. PMID12752120. S2CID20748122.
Apps SA, Rankin WA, Kurmis AP (February 2007). "Connexin 26 mutations in autosomal recessive deafness disorders: a review". International Journal of Audiology. 46 (2): 75–81. doi:10.1080/14992020600582190. PMID17365058. S2CID30841401.
Welch KO, Marin RS, Pandya A, Arnos KS (July 2007). "Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature". American Journal of Medical Genetics. Part A. 143A (14): 1567–73. doi:10.1002/ajmg.a.31701. PMID17431919. S2CID34944902.
Harris A, Locke D (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6.
Smith RJ, Shearer AE, Hildebrand MS, Van Camp G (January 2014). "Hereditary Hearing Loss and Deafness Overview". Deafness and Hereditary Hearing Loss Overview. University of Washington, Seattle. PMID20301607. NBK1434. In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A (1993). Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. PMID20301295.
