GJC2

GJC2, or gap junction protein gamma-2, is a human gene encoding a member of the connexin family that forms gap junction channels between neighboring cells. The encoded protein, commonly referred to as connexin-47, assembles into hexameric hemichannels (connexons) in the plasma membrane; docking of two connexons from adjacent cells creates a gap junction channel that allows the diffusion of ions and small metabolites.

Functionally, GJC2-derived connexin-47 is expressed in the central nervous system, particularly by oligodendrocytes and, to a lesser extent, by some astrocytes. It contributes to the formation and maintenance of myelin and to the metabolic and ionic coupling within glial networks. This intercellular communication supports homeostasis in myelinated regions and participates in the regulation of CNS development and function.

Genetically, mutations in GJC2 have been associated with a spectrum of neurological disorders marked by impaired myelination and motor dysfunction. Reported conditions include leukodystrophy and hereditary spastic paraplegia, with clinical presentations ranging from early motor signs to later-onset spasticity. Pathogenic variants can disrupt protein trafficking, docking, or channel gating, leading to compromised gap junction communication.

Research and clinical significance are ongoing to better understand how specific GJC2 variants affect glial communication and myelination, and how these insights might inform diagnosis, prognosis, and potential therapeutic strategies. Animal models with altered GJC2 function corroborate its role in CNS myelination and motor phenotypes.