ATP6V0A2 Gene - V-ATPase Subunit A2 | Function, Mutations & Diseases

The ATP6V0A2 gene encodes the a2 subunit of the vacuolar ATPase (V-ATPase) V0 domain, a multi-subunit proton pump responsible for acidification of intracellular organelles such as lysosomes, endosomes, and the Golgi apparatus. This subunit is essential for proton translocation and organelle acidification, which is critical for protein sorting, receptor recycling, and glycosylation. Mutations in ATP6V0A2 cause autosomal recessive cutis laxa type II (ARCL2) and are associated with congenital disorders of glycosylation (CDG).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• V-ATPase-mediated acidification (Reactome: R-HSA-1222556)

• Lysosome (KEGG: hsa04142)

• Metabolic pathways (KEGG: hsa01100)

The ATP6V0A2 protein (UniProt Q9Y487) is a 856-amino acid multi-pass membrane protein that forms part of the V0 domain of vacuolar ATPase. It contains a large cytoplasmic N-terminal domain and a C-terminal transmembrane region with multiple helices that constitute the proton channel. The a2 subunit is ubiquitously expressed but enriched in brain and kidney. It mediates proton translocation across membranes and is essential for maintaining acidic pH in intracellular compartments. Defects in this protein disrupt glycosylation and elastic fiber formation, leading to cutis laxa and CDG.