ATP4B
Chr 13ATPase H+/K+ transporting subunit beta
Also known as: ATP6B
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.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
191 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 113 | 0 | 113 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 50 | 14 | 0 | 64 |
Likely Benign | 0 | 6 | 0 | 0 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 56 | 130 | 0 | 186 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP4B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools