ATP2A3
Chr 17ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3
Also known as: SERCA3
This gene encodes a SERCA calcium-ATPase that transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen, contributing to calcium sequestration during muscular excitation and contraction. Mutations cause cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome) and X-linked dystonia-parkinsonism, both following X-linked inheritance patterns. The gene is highly intolerant to loss-of-function mutations, and the associated disorders primarily affect the nervous system with movement abnormalities and sensory deficits.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
ClinVar Variant Classifications
246 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 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 132 | 11 | 0 | 143 |
Likely Benign | 0 | 7 | 6 | 23 | 36 |
Benign | 0 | 4 | 3 | 18 | 25 |
Conflicting | — | 2 | |||
| Total | 0 | 143 | 46 | 41 | 232 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP2A3 · 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