ATP1A3

Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene.^[5][6]

ATP1A3
Identifiers
Aliases	ATP1A3, AHC2, DYT12, RDP, CAPOS, ATPase Na+/K+ transporting subunit alpha 3, ATP1A1, DEE99
External IDs	OMIM: 182350; MGI: 88107; HomoloGene: 113729; GeneCards: ATP1A3; OMA:ATP1A3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 41,966,582 bp[1] End 41,997,497 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 A3|7 13.73 cM Start 24,677,592 bp[2] End 24,705,383 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in superior frontal gyrus primary visual cortex right hemisphere of cerebellum prefrontal cortex apex of heart dorsolateral prefrontal cortex right frontal lobe Brodmann area 9 hypothalamus anterior cingulate cortex Top expressed in primary visual cortex dentate gyrus of hippocampal formation granule cell neural layer of retina superior frontal gyrus subiculum dorsomedial hypothalamic nucleus pontine nuclei cerebellar cortex dorsal tegmental nucleus habenula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function steroid hormone binding nucleotide binding chaperone binding P-type sodium:potassium-exchanging transporter activity metal ion binding P-type sodium:potassium-exchanging transporter activity involved in regulation of cardiac muscle cell membrane potential heparan sulfate proteoglycan binding D1 dopamine receptor binding hydrolase activity ATP binding amyloid-beta binding P-type potassium transmembrane transporter activity ion antiporter activity involved in regulation of presynaptic membrane potential Cellular component cytoplasm integral component of membrane dendritic spine neck extracellular vesicle Golgi apparatus membrane myelin sheath plasma membrane synapse sodium:potassium-exchanging ATPase complex axon dendritic spine head endoplasmic reticulum sarcolemma nucleus neuronal cell body membrane soma Biological process visual learning cellular response to steroid hormone stimulus regulation of cardiac conduction cardiac muscle contraction sodium ion transport cellular sodium ion homeostasis adult locomotory behavior sodium ion export across plasma membrane cell communication by electrical coupling involved in cardiac conduction response to glycoside ion transport memory cellular potassium ion homeostasis potassium ion transport ion transmembrane transport ionotropic glutamate receptor signaling pathway transport regulation of cardiac muscle cell membrane potential establishment or maintenance of transmembrane electrochemical gradient cerebral cortex development cellular response to retinoic acid cellular response to thyroid hormone stimulus regulation of resting membrane potential regulation of presynaptic membrane potential cellular response to amyloid-beta neuron projection maintenance potassium ion import across plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 478 232975 Ensembl ENSG00000105409 ENSMUSG00000040907 UniProt P13637 Q6PIC6 RefSeq (mRNA) NM_001256213 NM_001256214 NM_152296 NM_001290469 NM_144921 NM_001374627 RefSeq (protein) NP_001243142 NP_001243143 NP_689509 NP_001277398 NP_001361556 Location (UCSC) Chr 19: 41.97 – 42 Mb Chr 7: 24.68 – 24.71 Mb PubMed search [3] [4]
Wikidata
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Function

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.^[6] ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases.^[7]

Clinical significance

Disease causing variants of the ATP1A3 gene are known to cause a variety of movement disorders and epilepsies.^[8] The known associations include a variety of syndromes, in approximate order of presentation:

1. Malformation of Cortex Development, including polymicrogyria;^[7]
2. Developmental and epileptic encephalopathy 99 (DEE99);^[9]
3. Alternating hemiplegia of childhood 2 (AHC2);^[10]
4. Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome);
5. Very early-onset schizophrenia;^[11]
6. Rapid-onset dystonia parkinsonism (RDP, also known as DYT12);
7. Fever-induced paroxysmal weakness and encephalopathy (FIPWE);
8. Recurrent episodes of cerebellar ataxia (RECA).

In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.^[12]