ATP1A3

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]

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]