ATP6V0A1

Chr 17ADAR

ATPase H+ transporting V0 subunit a1

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

NCBI Gene: 535 ENSG00000033627 OMIM: 192130

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.

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. 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]

OMIM ResearchGenerating clinical summary…

AD/ARLOEUF 0.272 OMIM phenotypes

Clinical Summary— ATP6V0A1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 121 VUS of 171 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.27LOEUF

pLI 0.998

Z-score 5.56

OE 0.14 (0.08–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.74Z-score

OE missense 0.52 (0.47–0.57)

246 obs / 475.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.14 (0.08–0.27)

0≤0.351.4

Missense OE?0.52 (0.47–0.57)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 7 / 49.0Missense obs/exp: 246 / 475.8Syn Z: 1.04

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic5

VUS121

Likely Benign6

Conflicting2

Pathogenic

Likely Pathogenic

121

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	5	1	0	9
Likely Pathogenic	2	3	0	0	5
VUS	5	112	3	1	121
Likely Benign	0	3	0	3	6
Benign	0	0	0	0	0
Conflicting	—				2
Total	10	123	4	4	143

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

6 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap ATP6V0A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →