ATP6V0A2

Chr 12AR

ATPase H+ transporting V0 subunit a2

Also known as: A2, ARCL, ARCL2A, ATP6A2, ATP6N1D, J6B7, RTF, STV1

NCBI Gene: 23545 ENSG00000185344 UniProt: Q9Y487 OMIM: 611716

The ATP6V0A2 protein is a subunit of the V0 complex of vacuolar ATPase (V-ATPase), which acidifies intracellular compartments and maintains cellular pH homeostasis, with roles in endosomal pH sensing, Golgi function, and iron metabolism. Mutations cause autosomal recessive cutis laxa type IIA and wrinkly skin syndrome, connective tissue disorders affecting skin elasticity and structure. This gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a subunit of the vacuolar ATPase (v-ATPase), an heteromultimeric enzyme that is present in intracellular vesicles and in the plasma membrane of specialized cells, and which is essential for the acidification of diverse cellular components. V-ATPase is comprised of a membrane peripheral V(1) domain for ATP hydrolysis, and an integral membrane V(0) domain for proton translocation. The subunit encoded by this gene is a component of the V(0) domain. Mutations in this gene are a cause of both cutis laxa type II and wrinkly skin syndrome. [provided by RefSeq, Jul 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cutis laxa, autosomal recessive, type IIAMIM #219200

Wrinkly skin syndromeMIM #278250

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive cutis laxa type 2A · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ATP6V0A2