GJA8

GJA8 stands for gap junction protein alpha 8. The GJA8 gene encodes connexin 50 (Cx50), a member of the connexin family of gap junction proteins. Connexins form hexameric hemichannels called connexons; when docked with connexons from neighboring cells, they form gap junction channels that permit diffusion of ions and small metabolites.

Cx50 has four transmembrane domains, two extracellular loops and cytoplasmic N- and C- termini. It is predominantly expressed in the lens, especially in differentiating fiber cells, where it coexists with connexin 46 (Cx46, encoded by GJA3) to create intercellular channels that support lens growth, ion homeostasis and transparency.

Mutations in GJA8 are a common cause of inherited congenital cataracts. Pathogenic variants include missense, nonsense, splice-site, and frameshift changes; many exert dominant effects or cause loss of trafficking to the plasma membrane or altered channel function. The resulting impaired intercellular communication in lens tissue disrupts ionic balance and metabolism, contributing to cataract formation. Phenotypes vary across cataract presentations, from punctate to more severe lens opacities.

Genetic testing of GJA8 is part of the diagnostic evaluation for familial congenital cataracts. Research continues into how GJA8 mutations affect connexin interactions, lens physiology, and potential therapeutic approaches, including strategies to preserve or restore gap junction function in lens tissue.