GJB2

GJB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2ZW3, 3IZ1, 3IZ2, 5ERA, 5ER7
Identifiers
Aliases	GJB2, CX26, DFNA3, DFNA3A, DFNB1, DFNB1A, HID, KID, NSRD1, PPK, gap junction protein beta 2, BAPS
External IDs	OMIM: 121011; MGI: 95720; HomoloGene: 2975; GeneCards: GJB2; OMA:GJB2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q12.11 Start 20,187,463 bp[1] End 20,192,938 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 C3|14 30.1 cM Start 57,336,057 bp[2] End 57,342,159 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gingival epithelium human penis mucosa of pharynx skin of arm body of tongue oral cavity vulva skin of thigh pancreatic ductal cell skin of abdomen Top expressed in stria vascularis hair follicle meninges superior surface of tongue utricle left lobe of liver vestibular membrane of cochlear duct cervix lactiferous gland lip More reference expression data BioGPS n/a
Gene ontology Molecular function identical protein binding gap junction channel activity calcium ion binding metal ion binding Cellular component integral component of membrane connexin complex membrane plasma membrane cell junction gap junction endoplasmic reticulum-Golgi intermediate compartment cytoplasm cytosol lateral plasma membrane cell body perinuclear region of cytoplasm astrocyte projection integral component of plasma membrane Biological process hearing cell communication cell-cell signaling gap junction assembly response to ischemia female pregnancy ageing response to estradiol response to lipopolysaccharide response to retinoic acid response to progesterone cellular response to oxidative stress response to human chorionic gonadotropin response to antibiotic decidualization inner ear development transmembrane transport cellular response to glucagon stimulus cellular response to dexamethasone stimulus epididymis development gap junction-mediated intercellular transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2706 14619 Ensembl ENSG00000165474 ENSMUSG00000046352 UniProt P29033 Q00977 RefSeq (mRNA) NM_004004 NM_008125 RefSeq (protein) NP_003995 NP_032151 Location (UCSC) Chr 13: 20.19 – 20.19 Mb Chr 14: 57.34 – 57.34 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the GJB2 gene.

Function

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.^[5]

Gap junction beta-2 protein is a member of the connexin protein family and plays a crucial role in forming gap junctions, which are channels that allow the transport of nutrients, ions, and signaling molecules between adjacent cells.^[6] GJB2 is widely expressed throughout the body, with particularly important functions in the inner ear and skin. In the cochlea, GJB2 is believed to be essential for maintaining proper potassium ion levels and for the maturation of certain cochlear cells, both of which are critical for the process of converting sound waves into electrical nerve impulses.^[6] In the skin, GJB2 contributes to the growth, maturation, and stability of the epidermis.^[6]

Clinical significance

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).^[7] 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.^[8]

Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle.^[9] The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer,^[10] breast cancer,^[11] and bladder cancer.^[12] Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion^[13] and by stimulating the self-perpetuation ability of cancer stem cells.^[14]

See also

• Connexin
• Gap junction
• Vohwinkel syndrome
• Bart–Pumphrey syndrome

References

1. GRCh38: Ensembl release 89: ENSG00000165474 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046352 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa".
6. "GJB2 gene". MedlinePlus. U.S. National Library of Medicine.
7. Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, et al. (May 1997). "Connexin 26 mutations in hereditary non-syndromic sensorineural deafness". Nature. 387 (6628): 80–83. Bibcode:1997Natur.387...80K. doi:10.1038/387080a0. PMID 9139825. S2CID 4311728.
8. Zytsar MV, Barashkov NA, Bady-Khoo MS, Shubina-Olejnik OA, Danilenko NG, Bondar AA, et al. (August 2018). "Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia". BMC Medical Genetics. 19 (1): 138. doi:10.1186/s12881-018-0650-5. PMC 6081885. PMID 30086704.
9. Tanaka M, Grossman HB (February 2004). "Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells". Oncology Reports. 11 (2): 537–541. PMID 14719096. Archived from the original on 2021-08-01. Retrieved 2018-02-18.
10. Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, et al. (June 2010). "Clinical significance of the expression of connexin26 in colorectal cancer". Journal of Experimental & Clinical Cancer Research. 29 (1): 79. doi:10.1186/1756-9966-29-79. PMC 2907868. PMID 20565955.
11. Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, et al. (February 2013). "The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer". BMC Cancer. 13: 50. doi:10.1186/1471-2407-13-50. PMC 3583680. PMID 23374644.
12. Gee J, Tanaka M, Grossman HB (March 2003). "Connexin 26 is abnormally expressed in bladder cancer". The Journal of Urology. 169 (3): 1135–1137. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.
13. Kotini M, Mayor R (May 2015). "Connexins in migration during development and cancer". Developmental Biology. 401 (1): 143–151. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982.
14. Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V, et al. (February 2018). "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase". Nature Communications. 9 (1): 578. Bibcode:2018NatCo...9..578T. doi:10.1038/s41467-018-02938-1. PMC 5805730. PMID 29422613.

Further reading

• Kenneson A, Van Naarden Braun K, Boyle C (2002). "GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review". Genetics in Medicine. 4 (4): 258–274. doi:10.1097/00125817-200207000-00004. PMID 12172392.
• 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): 203–208. doi:10.1080/0036554021000028100. PMID 12701741. S2CID 2048758.
• Yotsumoto S, Hashiguchi T, Chen X, Ohtake N, Tomitaka A, Akamatsu H, et al. (April 2003). "Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome". The British Journal of Dermatology. 148 (4): 649–653. doi:10.1046/j.1365-2133.2003.05245.x. PMID 12752120. S2CID 20748122.
• 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. PMID 17365058. S2CID 30841401.
• 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): 1567–1573. doi:10.1002/ajmg.a.31701. PMID 17431919. S2CID 34944902.
• 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). "Deafness and Hereditary Hearing Loss Overview". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. PMID 20301607. NBK1434.
• Smith RJ, Sheffield AM, Van Camp G (2012-04-19). "Nonsyndromic Hearing Loss and Deafness, DFNA3". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. PMID 20301708. NBK1536.
• Smith RJ, Van Camp G (2014-01-02). "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. PMID 20301449. NBK1272.