GJB2 Gene: Connexin 26, Deafness, Mutations & Clinical Insights

The GJB2 gene encodes gap junction protein beta 2, commonly known as connexin 26 (Cx26). Connexin 26 is a transmembrane protein that forms gap junction channels, facilitating intercellular communication and the transfer of small molecules and ions. It is highly expressed in the cochlea, where it plays a critical role in potassium ion recycling, essential for normal hearing. Mutations in GJB2 are the most common cause of hereditary non-syndromic hearing loss, accounting for up to 50% of autosomal recessive deafness cases in many populations. Additionally, some mutations cause syndromic forms such as keratitis-ichthyosis-deafness (KID) syndrome and palmoplantar keratoderma with deafness.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Gap junction trafficking

• Potassium ion transport in cochlear hair cells

• Cell communication by electrical coupling

Connexin 26 (Cx26) is a 226-amino acid protein with four transmembrane domains, two extracellular loops, and one cytoplasmic loop. It forms hexameric connexons (hemichannels) that dock with connexons from adjacent cells to create gap junction channels. These channels allow the passage of ions, second messengers, and small metabolites up to ~1 kDa. In the inner ear, Cx26 is essential for maintaining the endocochlear potential and recycling potassium ions from hair cells back to the stria vascularis. Mutations disrupt these processes, leading to hearing impairment. The protein is also expressed in skin, where it contributes to epidermal differentiation and homeostasis.