ATP1A2
Chr 1ADARATPase Na+/K+ transporting subunit alpha 2
Also known as: DEE98, FARIMPD, FHM2, MHP2
The ATP1A2 gene encodes the alpha-2 subunit of Na+/K+-ATPase, which establishes and maintains electrochemical gradients of sodium and potassium ions across plasma membranes that are essential for neuronal excitability. Heterozygous mutations cause autosomal dominant familial hemiplegic migraine type 2 and alternating hemiplegia of childhood through a gain-of-function mechanism, while biallelic mutations result in autosomal recessive developmental and epileptic encephalopathy and severe fetal akinesia syndromes.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). 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.
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ATP1A2 · 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