ATP1A2

Chr 1

ATPase Na+/K+ transporting subunit alpha 2

Also known as: DEE98, FARIMPD, FHM2, MHP2

NCBI Gene: 477 ENSG00000018625 UniProt: P50993

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMigraine, familial hemiplegic, 2

UniProtAlternating hemiplegia of childhood 1

UniProtFetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies

UniProtDevelopmental and epileptic encephalopathy 98

Clinical highlights

Gene-disease validity (ClinGen)

hemiplegic migraine-developmental and epileptic encephalopathy spectrum · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

Multiple*

Mechanism· G2P

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GeneReview available — ATP1A2