ATP6V1C1

Chr 8

ATPase H+ transporting V1 subunit C1

Also known as: ATP6C, ATP6D, VATC, Vma5

NCBI Gene: 528 ENSG00000155097 UniProt: P21283

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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 is one of two genes that encode the V1 domain C subunit proteins and is found ubiquitously. This C subunit is analogous but not homologous to gamma subunit of F-ATPases. Previously, this gene was designated ATP6D. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOEUF 0.77

Clinical Summary— ATP6V1C1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 37 VUS of 59 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.40

OE 0.45 (0.28–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.71Z-score

OE missense 0.65 (0.56–0.76)

126 obs / 192.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.28–0.77)

0≤0.351.4

Missense OE?0.65 (0.56–0.76)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 10 / 22.2Missense obs/exp: 126 / 192.9Syn Z: -0.47

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS37

Likely Benign1

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	1
Likely Pathogenic	0	0	0
VUS	37	0	37
Likely Benign	0	1	1
Benign	0	0	0
Total	38	1	39

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap ATP6V1C1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →