ATP2B1
Chr 12ADATPase plasma membrane Ca2+ transporting 1
Also known as: MRD66, PMCA1, PMCA1kb
The ATP2B1 protein is a plasma membrane calcium ATPase that removes calcium ions from cells to maintain intracellular calcium homeostasis and regulate blood pressure through vascular smooth muscle function. Mutations cause autosomal dominant intellectual developmental disorder with onset typically in early development. This gene is extremely intolerant to loss-of-function variants (pLI >0.99), indicating that functional copies are essential for normal neurodevelopment.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
286 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 | 15 | 1 | 8 | 0 | 24 |
Likely Pathogenic | 17 | 9 | 1 | 0 | 27 |
VUS | 0 | 185 | 7 | 2 | 194 |
Likely Benign | 0 | 5 | 2 | 4 | 11 |
Benign | 0 | 1 | 0 | 4 | 5 |
Conflicting | — | 3 | |||
| Total | 32 | 201 | 18 | 10 | 264 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP2B1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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