ATP6AP2

Chr XXLR

ATPase H+ transporting accessory protein 2

This protein functions as a renin/prorenin cellular receptor and is essential for assembly of lysosomal V-type ATPases that acidify endo-lysosomal compartments and regulate protein degradation. Mutations cause X-linked recessive intellectual developmental disorder with syndromic features (Hedera type), congenital disorder of glycosylation type IIr, and potentially X-linked parkinsonism with spasticity. The gene is highly constrained against loss-of-function variants, reflecting its critical role in cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
XLRLOEUF 0.433 OMIM phenotypes
Clinical SummaryATP6AP2
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Gene-Disease Validity (ClinGen)
ATP6AP2-related disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.871
Z-score 2.80
OE 0.09 (0.030.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.66Z-score
OE missense 0.60 (0.510.72)
84 obs / 139.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.030.43)
00.351.4
Missense OE0.60 (0.510.72)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 1 / 11.1Missense obs/exp: 84 / 139.3Syn Z: 0.69

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATP6AP2 · 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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