ATP1A3

Chr 19

ATPase Na+/K+ transporting subunit alpha 3

Also known as: AHC2, CAPOS, DEE99, DYT12, RDP

NCBI Gene: 478ENSG00000105409UniProt: P13637

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDystonia 12
UniProtAlternating hemiplegia of childhood 2
UniProtCerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss
UniProtDevelopmental and epileptic encephalopathy 99

Clinical highlights

Gene-disease validity (ClinGen)
ATP1A3-associated neurological disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
64
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.06
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — ATP1A3
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.06LOEUF
pLI 1.000
Z-score 6.40
OE 0.00 (0.00–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
6.33Z-score
OE missense 0.29 (0.26–0.33)
186 obs / 635.1 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.06)
0≤0.351.4
Missense OE?0.29 (0.26–0.33)
0≤0.61.4
Synonymous OE?1.10
0≤1.21.6
LoF obs/exp: 0 / 47.7Missense obs/exp: 186 / 635.1Syn Z: -1.32

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ATP1A3 · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients