GJB2

Protein-coding gene in the species Homo sapiens

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

Gene location (Human)

Chr.	Chromosome 13 (human)^[1]

Band	13q12.11	Start	20,187,463 bp^[1]
Band	13q12.11	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]
Band	14 C3\|14 30.1 cM	End	57,342,159 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

human penis

body of tongue

oral cavity

vulva

pancreatic ductal cell

skin of abdomen

trigeminal ganglion

parotid gland

thymus

superior surface of tongue

Top expressed in

stria vascularis

hair follicle

meninges

superior surface of tongue

utricle

left lobe of liver

cervix

esophagus

corneal stroma

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	sensory perception of sound cell communication cell-cell signaling gap junction assembly response to ischemia female pregnancy human 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.

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).^[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]

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.^[13]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165474 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000046352 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (May 1997). "Connexin 26 mutations in hereditary non-syndromic sensorineural deafness". Nature. 387 (6628): 80–3. Bibcode:1997Natur.387...80K. doi:10.1038/387080a0. PMID 9139825. S2CID 4311728.
^ 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.
^ 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): 537–41. PMID 14719096. Archived from the original on 2021-08-01. Retrieved 2018-02-18.
^ Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, Hirakawa K (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.
^ Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, Papassotiropoulos B, Riemenschnitter C, Moch H, Varga Z (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.
^ Gee J, Tanaka M, Grossman HB (March 2003). "Connexin 26 is abnormally expressed in bladder cancer". The Journal of Urology. 169 (3): 1135–7. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.
^ Kotini M, Mayor R (May 2015). "Connexins in migration during development and cancer". Developmental Biology. 401 (1): 143–51. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982.
^ 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.
^ "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa".

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): 258–74. 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): 203–8. doi:10.1080/0036554021000028100. PMID 12701741. S2CID 2048758.
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. 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): 1567–73. 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). "Hereditary Hearing Loss and Deafness Overview". Deafness and Hereditary Hearing Loss Overview. University of Washington, Seattle. PMID 20301607. 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. PMID 20301295.
Smith RJ, Sheffield AM, Van Camp G (2012-04-19). "Nonsyndromic Hearing Loss and Deafness, DFNA3 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY". Nonsyndromic Hearing Loss and Deafness, DFNA3. University of Washington, Seattle. PMID 20301708. NBK1536. In GeneReviews
Smith RJ, Van Camp G (2014-01-02). "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss". Nonsyndromic Hearing Loss and Deafness, DFNB1. University of Washington, Seattle. PMID 20301449. NBK1272. In GeneReviews

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin