GJB2 Gene

Last updated on: 25.12.2021

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The GJB2 gene (GJB2 is the acronym for gap junction protein beta 2) is a protein-coding gene located on chromosome 13q12.11. GJB2 encodes connexin 26, a family member of the gap junction proteins. Mutations in the GJB2 gene are associated with various diseases. For example, isolated deafness can occur depending on the location of the mutation within the GJB2 gene. Connexin (Cx) 26 mutations induce more than 50% of the incidence of non-syndromic deafness in different human populations. Other mutations lead to various forms of palmoplantar keratosis as well as Hysterix-like ichthyosis, with or without deafness. Furthermore, there may be reduced immune defenses and increased carcinogenic potential.

Diseases associated with GJB2 include:

The large number of disease mutants provides unique opportunities to gain insight into the underlying function of gap junction proteins and their channels in the normal and pathogenic physiology of the cochlea and epidermis.

General information
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Connexins (Cxs), also called gap junction proteins, are phylogenetically very old, integral membrane-spanning proteins and function, among other things, as structural proteins in the hexamer structures of gap junctions. Connexins are named after their molecular weight (e.g. Connexin 26 with 26 kDa). They are involved in tissue homeostasis and act at multiple levels of communication.

Gap junctions are dodecameric channels that connect the cytoplasm of adjacent cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Gap junctions allow intercellular communication and enable cells to have synchronized responses to various intercellular signals. This is accomplished by regulating the influx or efflux of small molecules (< 1000 Da) as well as ions between the cytoplasms of adjacent cells. In the skin, gap junctions are involved in the coordination of growth and differentiation of keratinocytes, among other things (see cell contacts below).

To date, more than 30 different connexins have been described in vertebrates. The most important connexins in human skin are connexin 43 (Cx43) and connexin 26 (Cx26).

  • Cx43 is expressed mainly in the cells of the suprabasal layers and is considered the major gap junction subunit of the interfollicular epidermis.
  • Cx26 is expressed in the basal cell layers of the hair follicle and sweat gland epithelium and is considered to regulate keratinocyte homeostasis during rapid growth or differentiation.

Because connexin 26 is expressed in the cochela in addition to the basal layers of acral epidermis, this gene links palmoplantar hyperkeratosis with hearing loss (Lam MW et al. 2020). Cx26 plays an essential role in postnatal maturation of the cochlea (Beyer EC et al. 2018; Heathcote K et al. 2000; Wu X et al. 2019).

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  1. Beyer EC et al. (2018) Gap junction gene and protein families: connexins, innexins and pannexins. Biochim. Biophys Acta Biomembr 1860: 5-8.
  2. Heathcote K et al (2000) A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis. J Med Genet 37: 50-51.
  3. Lam MW et al (2020) Connexin 26 missense mutation resulting in syndromic hearing loss with palmoplantar keratoderma. Int J Dermatol 59: e454-e455.
  4. Lee JR et al (2009) White connexin-26 mutations in deafness and skin disease. Expert Rev Mol Med 11:e35.
  5. Moscato S et al (2018) Connexin 26 expression in mammalian cardiomyocytes. Sci Rep 8:13975.
  6. Wu X et al. (2019) tructure and Function of Cochlear Gap Junctions and Implications for the Translation of Cochlear Gene Therapies. Front Cell Neurosci. 13: 529.
  7. Xu J et al. (2013) The role of connexins in ear and skin physiology - Functional insights from disease-associated mutation. Biomembranes 1828:167-178

Last updated on: 25.12.2021