ATP6AP2

Chr XXLR

ATPase H+ transporting accessory protein 2

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

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

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
0
Active trials
10
Pubs (1 yr)
78
P/LP submissions
3%
P/LP missense
0.43
LOEUF
Mechanism
Clinical SummaryATP6AP2
🧬
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
72 unique Pathogenic / Likely Pathogenic· 133 VUS of 410 total submissions

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

410 submitted variants in ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic2
VUS133
Likely Benign95
Benign17
Conflicting7
70
Pathogenic
2
Likely Pathogenic
133
VUS
95
Likely Benign
17
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
68
1
70
Likely Pathogenic
0
1
1
0
2
VUS
0
107
25
1
133
Likely Benign
0
2
46
47
95
Benign
0
0
16
1
17
Conflicting
7
Total011115650324

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

View 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →