ATP6V1A
Chr 3ARADATPase H+ transporting V1 subunit A
Also known as: ARCL2D, ATP6A1, ATP6V1A1, DEE93, HO68, IECEE3, VA68, VPP2
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.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
The Badonyi & Marsh model scores loss-of-function highest, but genomic evidence most strongly supports gain-of-function as the primary mechanism.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
489 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 13 | 29 | 0 | 42 |
Likely Pathogenic | 0 | 13 | 1 | 0 | 14 |
VUS | 16 | 193 | 11 | 4 | 224 |
Likely Benign | 0 | 1 | 70 | 92 | 163 |
Benign | 0 | 1 | 18 | 3 | 22 |
Conflicting | — | 4 | |||
| Total | 16 | 221 | 129 | 99 | 469 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP6V1A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools