ATP6V0A1

Chr 17

ATPase H+ transporting V0 subunit a1

Also known as: ATP6N1, ATP6N1A, DEE104, NEDEBA, Stv1, VPP1, Vph1, a1

NCBI Gene: 535 ENSG00000033627 UniProt: Q93050

The protein is a subunit of the V0 complex of vacuolar ATPase that acidifies intracellular organelles including lysosomes, endosomes, and synaptic vesicles, which is essential for neuronal development and connectivity. Mutations cause developmental and epileptic encephalopathy and neurodevelopmental disorder with epilepsy and brain atrophy through both autosomal dominant and autosomal recessive inheritance patterns. The high constraint scores indicate the gene is highly intolerant to loss-of-function variants, suggesting mutations can cause disease through multiple mechanisms depending on the specific variant type.

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. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This gene encodes one of three A subunit proteins and the encoded protein is associated with clathrin-coated vesicles. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 104

UniProtNeurodevelopmental disorder with epilepsy and brain atrophy

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429