GJC3 Gene: Connexin 30.3 in Hearing & Skin | NCBI, UniProt, OMIM

GJC3 (Gap junction protein gamma 3), also known as connexin 30.3 (CX30.3) or GJB4, encodes a member of the connexin protein family. Connexins assemble into gap junction channels that facilitate direct intercellular communication by allowing the transfer of ions and small molecules. GJC3 is expressed in the skin, cochlea, and other tissues, and plays a critical role in epidermal differentiation and auditory function. Mutations in GJC3 are associated with erythrokeratodermia variabilis et progressiva (EKVP) and autosomal dominant nonsyndromic hearing loss (DFNA2).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Gap junction trafficking and assembly (Reactome: R-HSA-190828)

• Connexin transport to the plasma membrane (Reactome: R-HSA-190840)

• Keratinocyte differentiation (KEGG: hsa04540)

GJC3 encodes connexin 30.3, a 266-amino acid transmembrane protein with four alpha-helical domains, two extracellular loops, and a cytoplasmic C-terminus. It forms hexameric hemichannels (connexons) that dock with counterparts on adjacent cells to create gap junction channels. In the epidermis, Cx30.3 is expressed in the granular layer and contributes to calcium homeostasis and barrier formation. In the inner ear, it participates in potassium recycling in the stria vascularis and supporting cells. Mutations that alter channel gating, trafficking, or assembly lead to skin hyperkeratosis and progressive hearing loss.