ATP6V0A2

Chr 12AR

ATPase H+ transporting V0 subunit a2

Also known as: A2, ARCL, ARCL2A, ATP6A2, ATP6N1D, J6B7, RTF, STV1

The ATP6V0A2 protein is a subunit of the V0 complex of vacuolar ATPase (V-ATPase), which acidifies intracellular compartments and maintains cellular pH homeostasis, with roles in endosomal pH sensing, Golgi function, and iron metabolism. Mutations cause autosomal recessive cutis laxa type IIA and wrinkly skin syndrome, connective tissue disorders affecting skin elasticity and structure. This gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.752 OMIM phenotypes
Clinical SummaryATP6V0A2
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Gene-Disease Validity (ClinGen)
autosomal recessive cutis laxa type 2A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 203 VUS of 500 total submissions
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GeneReview available — ATP6V0A2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 2.94
OE 0.54 (0.390.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.95Z-score
OE missense 0.88 (0.810.95)
412 obs / 469.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.390.75)
00.351.4
Missense OE0.88 (0.810.95)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 25 / 46.7Missense obs/exp: 412 / 469.6Syn Z: -0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveATP6V0A2-related wrinkly skin syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.77top 25%
LOF
0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic25
VUS203
Likely Benign195
Benign32
Conflicting4
25
Pathogenic
25
Likely Pathogenic
203
VUS
195
Likely Benign
32
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
5
0
25
Likely Pathogenic
20
1
4
0
25
VUS
2
185
13
3
203
Likely Benign
0
1
110
84
195
Benign
0
0
32
0
32
Conflicting
4
Total4218716487484

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP6V0A2 · 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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