ATP4B

Chr 13

ATPase H+/K+ transporting subunit beta

Also known as: ATP6B

NCBI Gene: 496 ENSG00000186009 UniProt: P51164 OMIM: 137217

The beta subunit of gastric H+/K+-ATPase functions as a proton pump that exchanges hydrogen and potassium ions across the membrane of gastric parietal cells, playing structural and regulatory roles in gastric acid secretion. Mutations cause congenital chloride diarrhea with gastric hypochlorhydria, inherited in an autosomal recessive pattern. This gene shows low constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes the beta subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.42

OE 0.60 (0.36–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.96 (0.85–1.10)

169 obs / 175.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.36–1.05)

0≤0.351.4

Missense OE?0.96 (0.85–1.10)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 9 / 14.9Missense obs/exp: 169 / 175.2Syn Z: -0.05

Background carrier burden — how many people carry a rare variant somewhere in ATP4B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

403 rare PASS variants

Rare truncating (LoF)

1 in 2,100

59 rare PASS variants

Rare synonymous (reference)

1 in 200

167 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP4B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 2,200
South Asian	~43k	1 in 96	1 in 1,600
Remaining (unassigned)	~30k	1 in 73	1 in 4,300
European (Finnish)	~27k	1 in 430	≈ 1 in 25,000
Admixed American	~22k	1 in 79	1 in 3,700
African / African American	~21k	1 in 78	1 in 1,400
East Asian	~20k	1 in 130	none seen
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 95	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓