ATP6AP2

Chr XXLR

ATPase H+ transporting accessory protein 2

Also known as: (P)RR, APT6M8-9, ATP6IP2, ATP6M8-9, CDG2R, ELDF10, HT028, M8-9

NCBI Gene: 10159 ENSG00000182220 UniProt: O75787 OMIM: 300556

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Parkinsonism with spasticity, X-linkedMIM #300911

XLR

Congenital disorder of glycosylation, type IIrMIM #301045

XLR

Intellectual developmental disorder, X-linked syndromic, Hedera typeMIM #300423

XLR

Clinical highlights

Gene-disease validity (ClinGen)

ATP6AP2-related disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.43

LOEUF

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Mechanism