ATP6V0A2

ATP6V0A2, also known as vacuolar H+-ATPase 100 kDa subunit a isoform 2, is a gene encoding a protein that is a component of the V0 domain of the vacuolar ATPase (V-ATPase). The V-ATPase is a multi-subunit enzyme responsible for acidifying intracellular compartments in eukaryotic cells. It couples the energy of ATP hydrolysis to proton transport across intracellular membranes, thereby contributing to numerous cellular processes including endocytosis, protein degradation, and synaptic vesicle acidification.

The ATP6V0A2 protein is a transmembrane protein that is essential for the proper assembly and function of the V0 domain, which forms the proton channel. Different isoforms of the "a" subunit (ATP6V0A1-4) contribute to tissue-specific expression and targeting of the V-ATPase to various organelles. ATP6V0A2 is primarily expressed in bone and skin.

Mutations in the ATP6V0A2 gene are associated with autosomal recessive cutis laxa type II (ARCL2), also known as wrinkly skin syndrome. This condition is characterized by loose, wrinkled skin, skeletal abnormalities, developmental delay, and other systemic manifestations. The mutations typically disrupt the proper function of the V-ATPase, leading to defects in collagen processing and extracellular matrix organization, contributing to the characteristic skin phenotype. Other less common phenotypes may also result from ATP6V0A2 mutations.

Research into ATP6V0A2 is ongoing, focusing on understanding the precise mechanisms by which mutations in this gene lead to the diverse clinical features of ARCL2 and related disorders, and exploring potential therapeutic strategies to address these conditions.