ATP6V0C
Chr 16ADATPase H+ transporting V0 subunit c
Also known as: ATP6C, ATP6L, ATPL, EPEO3, VATL, VPPC, Vma3
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
99 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 | 4 | 7 | 28 | 0 | 39 |
Likely Pathogenic | 3 | 7 | 4 | 0 | 14 |
VUS | 4 | 20 | 17 | 0 | 41 |
Likely Benign | 0 | 0 | 0 | 2 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 11 | 34 | 49 | 2 | 96 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP6V0C · 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