GJB1 Gene (Connexin 32) - X-linked Charcot-Marie-Tooth Disease | NCBI, OMIM

The GJB1 gene encodes gap junction protein beta 1, also known as connexin 32 (Cx32). This protein forms gap junctions that facilitate intercellular communication by allowing the passage of small molecules and ions. GJB1 is predominantly expressed in Schwann cells of the peripheral nervous system, where it plays a critical role in myelination and nerve conduction. Mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease (CMTX1), a hereditary peripheral neuropathy characterized by progressive muscle weakness and atrophy. The gene is located on the X chromosome, leading to distinct clinical presentations in males and females.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Gap junction trafficking and assembly

• Cell-cell communication

• Myelination pathway (Schwann cell)

Connexin 32 (Cx32) is a four-pass transmembrane protein that oligomerizes into hexameric connexons (hemichannels). These connexons dock with counterparts on adjacent cells to form gap junction channels, allowing the diffusion of ions and small molecules (<1 kDa). In Schwann cells, Cx32 forms reflexive gap junctions between the layers of the myelin sheath, facilitating nutrient and signaling molecule transport. Mutations in GJB1 disrupt these channels, leading to demyelination and axonal degeneration characteristic of CMTX1. The protein is also expressed in other tissues, but the peripheral neuropathy phenotype is most prominent.