ATP6AP1

Chr X

ATPase H+ transporting accessory protein 1

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

NCBI Gene: 537 ENSG00000071553 UniProt: Q15904

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Vacuolar ATPase (V-ATPase) is comprised of a cytosolic V1 (site of the ATP catalytic site) and a transmembrane V0 domain. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. The encoded protein of this gene may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules. This protein may also play a role in early development. [provided by RefSeq, Aug 2013]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— ATP6AP1

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Gene-Disease Validity (ClinGen)

congenital disorder of glycosylation type II · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 0.991

Z-score 3.47

OE 0.00 (0.00–0.21)

Highly constrained

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

Missense Constraint?

1.53Z-score

OE missense 0.68 (0.59–0.79)

127 obs / 185.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.21)

0≤0.351.4

Missense OE?0.68 (0.59–0.79)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 14.1Missense obs/exp: 127 / 185.7Syn Z: 0.22

This gene — mechanism propensity

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.