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 and a smaller glycoprotein subunit. 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:
  1. Malformation of Cortex Development, including polymicrogyria;
  2. Developmental and epileptic encephalopathy 99 ;
  3. Alternating hemiplegia of childhood 2 ;
  4. Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss ;
  5. Very early-onset schizophrenia;
  6. Rapid-onset dystonia parkinsonism ;
  7. Fever-induced paroxysmal weakness and encephalopathy ;
  8. Recurrent episodes of cerebellar ataxia.
In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.