ATP6V1C1

Chr 8

ATPase H+ transporting V1 subunit C1

Also known as: ATP6C, ATP6D, VATC, Vma5

This protein is a subunit of vacuolar ATPase (V-ATPase) that hydrolyzes ATP to acidify intracellular compartments, which is essential for protein sorting, endocytosis, and synaptic vesicle function. Mutations cause autosomal recessive neuronal ceroid lipofuscinosis, a progressive neurodegenerative disorder affecting the brain with childhood onset. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.77
Clinical SummaryATP6V1C1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 42 VUS of 104 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.40
OE 0.45 (0.280.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.71Z-score
OE missense 0.65 (0.560.76)
126 obs / 192.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.280.77)
00.351.4
Missense OE0.65 (0.560.76)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 10 / 22.2Missense obs/exp: 126 / 192.9Syn Z: -0.47

ClinVar Variant Classifications

104 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic2
VUS42
Likely Benign1
39
Pathogenic
2
Likely Pathogenic
42
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
38
0
39
Likely Pathogenic
0
0
2
0
2
VUS
0
37
5
0
42
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total03845184

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP6V1C1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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