ATP1A1

Chr 1AD

ATPase Na+/K+ transporting subunit alpha 1

Also known as: CMT2DD, HOMGSMR2

NCBI Gene: 476ENSG00000163399UniProt: P05023OMIM: 182310

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 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2DDMIM #618036
AD
Hypomagnesemia, seizures, and impaired intellectual development 2MIM #618314
AD

Clinical highlights

Gene-disease validity (ClinGen)
Charcot-Marie-tooth disease, axonal, type 2DD · 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.
1
Active trials
79
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.12
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
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GeneReview available — ATP1A1
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 6.43
OE 0.04 (0.01–0.12)
Highly constrained

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

Missense Constraint?
6.22Z-score
OE missense 0.29 (0.25–0.32)
171 obs / 599.1 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.04 (0.01–0.12)
0≤0.351.4
Missense OE?0.29 (0.25–0.32)
0≤0.61.4
Synonymous OE?1.12
0≤1.21.6
LoF obs/exp: 2 / 52.0Missense obs/exp: 171 / 599.1Syn Z: -1.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ATP1A1 · 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