ATP6V0C

Chr 16AD

ATPase H+ transporting V0 subunit c

Also known as: ATP6C, ATP6L, ATPL, EPEO3, VATL, VPPC, Vma3

NCBI Gene: 527 ENSG00000185883 UniProt: P27449 OMIM: 108745

The protein forms the proton-conducting pore of the V0 complex in vacuolar H+-ATPase, which acidifies intracellular compartments and maintains cellular pH homeostasis. Mutations cause autosomal dominant early-onset epilepsy with or without developmental delay, affecting the nervous system primarily in infancy or early childhood. The gene shows moderate constraint against loss-of-function variants (pLI 0.74, LOEUF 0.67), indicating that complete loss of function is somewhat selected against in the population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. This gene encodes the V0 subunit c. Alternative splicing results in transcript variants. Pseudogenes have been identified on chromosomes 6 and 17. [provided by RefSeq, Nov 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 3, with or without developmental delayMIM #620465

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ATP6V0C