ATP6V0C

Chr 16AD

ATPase H+ transporting V0 subunit c

Also known as: ATP6C, ATP6L, ATPL, EPEO3, VATL, VPPC, Vma3

NCBI Gene: 527ENSG00000185883UniProt: P27449

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. This gene encodes the V0 subunit c. Alternative splicing results in transcript variants. Pseudogenes have been identified on chromosomes 6 and 17. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 3, with or without developmental delayMIM #620465
AD
96
ClinVar variants
53
Pathogenic / LP
0.74
pLI score
0
Active trials
Clinical Summary— ATP6V0C
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 40 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.742
Z-score 1.96
OE 0.00 (0.00–0.67)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.99Z-score
OE missense 0.19 (0.14–0.28)
21 obs / 108.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.19 (0.14–0.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 0 / 4.5Missense obs/exp: 21 / 108.5Syn Z: -0.99

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic14
VUS40
39
Pathogenic
14
Likely Pathogenic
40
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
6
29
0
39
Likely Pathogenic
2
7
5
0
14
VUS
3
19
18
0
40
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total93252093

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.

Gene2Phenotype Curations

ATP6V0C-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epilepsy, early-onset, 3, with or without developmental delay

MIM #620465

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variants in ATP6V0C are associated with Dravet-like developmental and epileptic encephalopathy.
Rong M et al.·Epilepsia
2025Case report
ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy.
Mattison KA et al.·Brain
2023
ATP6V0C gene variants were identified in individuals with epilepsy, with or without developmental delay.
Zhao S et al.·J Hum Genet
2023
High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C.
Huang X et al.·J Periodontol
2020
A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay.
Mucha BE et al.·Genet Med
2019
Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia.
Fasham J et al.·Am J Hum Genet
2026
ATP6V0C knockdown in neuroblastoma cells alters autophagy-lysosome pathway function and metabolism of proteins that accumulate in neurodegenerative disease.
Mangieri LR et al.·PLoS One
2014
Systematic microRNA analysis identifies ATP6V0C as an essential host factor for human cytomegalovirus replication.
Pavelin J et al.·PLoS Pathog
2013
Bcl-2-dependent synthetic lethal interaction of the IDF-11774 with the V0 subunit C of vacuolar ATPase (ATP6V0C) in colorectal cancer.
Kim BK et al.·Br J Cancer
2018
Lysosomal dysfunction-derived autophagy impairment of gingival epithelial cells in diabetes-associated periodontitis with altered protein acetylation.
Liu H et al.·Cell Signal
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools