ATP6V1B1

Chr 2AR

ATPase H+ transporting V1 subunit B1

Also known as: ATP6B1, DRTA2, RTA1B, VATB, VMA2, VPP3

NCBI Gene: 525 ENSG00000116039 UniProt: P15313 OMIM: 192132

This gene encodes the B1 subunit of vacuolar H+-ATPase, a multisubunit enzyme that acidifies intracellular compartments and, in renal intercalated cells, secretes protons into urine for urinary acidification. Mutations cause autosomal recessive distal renal tubular acidosis with sensorineural hearing loss, a condition affecting kidney function and hearing. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain B subunit isoforms and is found in the kidney. Mutations in this gene cause distal renal tubular acidosis associated with sensorineural deafness. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.951 OMIM phenotype

Clinical Summary— ATP6V1B1

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Gene-Disease Validity (ClinGen)

renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

128 unique Pathogenic / Likely Pathogenic· 265 VUS of 875 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP6V1B1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.77

OE 0.64 (0.44–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.23Z-score

OE missense 0.96 (0.88–1.06)

297 obs / 308.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.44–0.95)

0≤0.351.4

Missense OE?0.96 (0.88–1.06)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 18 / 28.2Missense obs/exp: 297 / 308.5Syn Z: 0.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveATP6V1B1-related distal renal tubular acidosis with deafnessLOFAR

This gene — mechanism propensity

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

0.78top 25%

GOF

0.5954th %ile

LOF

0.3068th %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

875 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55

Likely Pathogenic73

VUS265

Likely Benign391

Benign45

Conflicting32

Pathogenic

Likely Pathogenic

265

VUS

391

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	53	1	1	0	55
Likely Pathogenic	64	7	1	1	73
VUS	2	233	16	14	265
Likely Benign	0	3	168	220	391
Benign	0	1	38	6	45
Conflicting	—				32
Total	119	245	224	241	861

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap ATP6V1B1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →