ATP6V1G1

Chr 9

ATPase H+ transporting V1 subunit G1

Also known as: ATP6G, ATP6G1, ATP6GL, ATP6J, Vma10

NCBI Gene: 9550 ENSG00000136888 UniProt: O75348

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, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of three V1 domain G subunit proteins. Pseudogenes of this gene have been characterized. [provided by RefSeq, Jul 2008]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.6

Missense Z

1.25

LOEUF

Clinical Summary— ATP6V1G1

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Population Constraint (gnomAD)

Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

28 Pathogenic / Likely Pathogenic· 26 VUS of 56 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

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.

1.25LOEUF

pLI 0.104

Z-score 1.23

OE 0.40 (0.16–1.25)

Tolerant

Highly tolerant — LoF variants common in population

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.

0.62Z-score

OE missense 0.77 (0.60–0.99)

43 obs / 56.1 exp

Tolerant

Mild missense constraint

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.0.40 (0.16–1.25)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.60–0.99)

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.0.82

0≤1.21.6

LoF obs/exp: 2 / 5.0Missense obs/exp: 43 / 56.1Syn Z: 0.63

0.80top 25%

GOF

0.5758th %ile

LOF

0.2091th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.