ATP6V1A

Chr 3

ATPase H+ transporting V1 subunit A

Also known as: ARCL2D, ATP6A1, ATP6V1A1, DEE93, HO68, IECEE3, VA68, VPP2

NCBI Gene: 523 ENSG00000114573 UniProt: P38606

This gene encodes a catalytic subunit of vacuolar H+-ATPase (V-ATPase), which acidifies intracellular organelles and maintains cellular pH homeostasis essential for protein sorting, endocytosis, and synaptic vesicle function. Mutations cause autosomal recessive cutis laxa type IID and developmental and epileptic encephalopathy 93, with both autosomal recessive and dominant inheritance patterns reported. The pathogenic mechanism involves disruption of organellar acidification, which impairs intracellular iron homeostasis and may affect neurite development and synaptic connectivity.

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 encoded protein is one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCutis laxa, autosomal recessive, 2D

UniProtEpileptic encephalopathy, infantile or early childhood, 3

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive cutis laxa type 2D · ARLimitednot for standalone diagnostic reporting

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

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P/LP missense

0.36

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

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