ATP2B3
Chr XXLRATPase plasma membrane Ca2+ transporting 3
Also known as: CFAP39, CLA2, OPCA, PMCA3, PMCA3a, SCAX1
This gene encodes plasma membrane calcium ATPase isoform 3, which uses ATP to transport cytosolic calcium ions across the plasma membrane to maintain basal intracellular calcium levels at presynaptic terminals. Mutations cause X-linked spinocerebellar ataxia type 1 through an X-linked recessive inheritance pattern. The pathogenic mechanism appears to involve gain-of-function effects that disrupt normal calcium homeostasis at synapses.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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
300 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 | 62 | 0 | 62 |
Likely Pathogenic | 0 | 3 | 2 | 0 | 5 |
VUS | 3 | 109 | 18 | 0 | 130 |
Likely Benign | 0 | 31 | 7 | 27 | 65 |
Benign | 0 | 2 | 6 | 11 | 19 |
Conflicting | — | 2 | |||
| Total | 3 | 145 | 95 | 38 | 283 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP2B3 · 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
External Resources
Links to major genomics databases and tools