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…

XLRLOEUF 0.433 OMIM phenotypes

Clinical Summary— ATP6AP2

🧬

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.

📋

ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 126 VUS of 333 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.871

Z-score 2.80

OE 0.09 (0.03–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.66Z-score

OE missense 0.60 (0.51–0.72)

84 obs / 139.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.43)

0≤0.351.4

Missense OE?0.60 (0.51–0.72)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 1 / 11.1Missense obs/exp: 84 / 139.3Syn Z: 0.69

ClinVar Variant Classifications

333 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS126

Likely Benign93

Benign17

Conflicting6

Pathogenic

Likely Pathogenic

126

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	1	1	4
Likely Pathogenic	0	1	0	0	1
VUS	0	107	18	1	126
Likely Benign	1	2	44	46	93
Benign	0	0	16	1	17
Conflicting	—				6
Total	2	111	79	49	247

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

75 pathogenic / likely-pathogenic (of 82) ClinVar copy-number / structural variants overlap ATP6AP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →