ATP6AP1

Chr XXLR

ATPase H+ transporting accessory protein 1

Also known as: 16A, ATP6IP1, ATP6S1, Ac45, CF2, VATPS1, XAP-3, XAP3

The protein is an accessory subunit of the vacuolar ATPase complex that acidifies intracellular organelles including neuroendocrine secretory vesicles and is involved in membrane trafficking and intracellular iron homeostasis. Mutations cause X-linked recessive immunodeficiency 47. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.211 OMIM phenotype
Clinical SummaryATP6AP1
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Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation type II · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.991
Z-score 3.47
OE 0.00 (0.000.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.53Z-score
OE missense 0.68 (0.590.79)
127 obs / 185.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.21)
00.351.4
Missense OE0.68 (0.590.79)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 0 / 14.1Missense obs/exp: 127 / 185.7Syn Z: 0.22
DN
0.3097th %ile
GOF
0.2795th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATP6AP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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