ATP1A3

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

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. ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases.

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

In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.
 * 1) Malformation of Cortex Development, including polymicrogyria;
 * 2) Developmental and epileptic encephalopathy 99 (DEE99);
 * 3) Alternating hemiplegia of childhood 2 (AHC2);
 * 4) Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome);
 * 5) Very early-onset schizophrenia;
 * 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).