ATP6V1B2

Chr 8AD

ATPase H+ transporting V1 subunit B2

Also known as: ATP6B1B2, ATP6B2, DOOD, HO57, VATB, VPP3, Vma2, ZLS2

ATP6V1B2 encodes a non-catalytic subunit of the V1 complex of vacuolar H+-ATPase, which acidifies intracellular compartments and, in some cells, the extracellular environment. Autosomal dominant mutations cause congenital deafness with onychodystrophy and Zimmermann-Laband syndrome 2. The gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating that such variants are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.292 OMIM phenotypes
Clinical SummaryATP6V1B2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.992
Z-score 4.58
OE 0.13 (0.060.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.49Z-score
OE missense 0.59 (0.520.67)
172 obs / 291.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.13 (0.060.29)
00.351.4
Missense OE0.59 (0.520.67)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 4 / 31.9Missense obs/exp: 172 / 291.4Syn Z: -1.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongATP6V1B2-related Zimmermann-Laband syndromeDNAD
DN
0.4884th %ile
GOF
0.3491th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.29

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFTaken together, these results suggest that ATP6V1B2 c.1516 C>T mutation is a haploinsufficient mutation.PMID:24913193

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATP6V1B2 · 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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