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ATP1A2

ATPase Na+/K+ transporting subunit alpha 2

The ATP1A2 gene provides instructions for a key component of the Na+/K+ ATPase pump, vital for maintaining proper ion balance and nerve cell communication in the brain. The ATP1A2 gene encodes the alpha-2 subunit of the sodium-potassium ATPase, an enzyme that transports sodium and potassium ions across cell membranes.

Chromosome 1q23.2 Various HGNC:800 Tier C
ATP1A2 1q23.2 p arm q arm 1

ATP1A2 is located on the long (q) arm of chromosome 1, at band 1q23.2. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
ATP1A2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ATP1A2 gene, also known as ATPase Na+/K+ transporting subunit alpha 2, plays a crucial role in the human nervous system. It provides the genetic blueprint for one part of an important protein called the Na+/K+ ATPase pump. This protein is essential for managing the flow of charged atoms, or ions, in and out of cells, which is fundamental for nerve impulses and overall brain function.

What the gene does

The protein produced from the ATP1A2 gene is the alpha-2 subunit of the Na+/K+ ATPase. This enzyme uses energy derived from adenosine triphosphate (ATP) to actively transport sodium ions out of cells and potassium ions into cells. This ion exchange is critical for establishing and maintaining the electrical gradient across cell membranes. In the nervous system, Na+/K+ ATPases containing the alpha-2 subunit are predominantly found in glial cells, which are support cells for neurons. Within glia, this protein helps regulate the concentration of neurotransmitters in the spaces between neurons, ensuring efficient and accurate signal transmission. It also aids in removing excess potassium ions from these extracellular spaces, which is vital for preventing neuronal hyperexcitability. Proper function of the ATP1A2-encoded protein is therefore indispensable for normal neuronal activity.

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Chromosome location

The ATP1A2 gene is situated on chromosome 1, specifically at position 1q23.2. This location refers to the long (q) arm of chromosome 1, within region 2, band 3, and sub-band 2. The precise genomic address helps in identifying and studying this gene.

Protein structure

The ATP1A2 gene codes for a protein that is 1020 amino acids long. Key regions within this protein include a disordered region spanning amino acids 1-31 and another disordered region from amino acids 212-231. There is also a specific region involved in the interaction with phosphoinositide-3 kinase, located at amino acids 80-82.

Domain map · 1,020 amino acids
Interaction with phosphoinositide-3 kinase (80–82)Interaction with phosp80–821~5101,020
Region - functional region
🧬 Explore 3D structure on AlphaFold
UniProt:P50993Length:1,020 aaStructure:AlphaFold

Key variants

Variants within the ATP1A2 gene can influence the structure and function of the Na+/K+ ATPase alpha-2 subunit, leading to altered ion transport and neuronal signalling. These genetic changes can range from single amino acid substitutions to larger alterations, potentially impacting the protein's efficiency or stability. The clinical consequences of these variants are diverse and can manifest in various neurological conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ATP1A2.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1234C>T
single nucleotide variant
 p.Arg412Ter Pathogenic/Likely pathogenic ★★☆☆ Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies
c.1453A>T
single nucleotide variant
 p.Lys485Ter Pathogenic ★★☆☆ Familial hemiplegic migraine
c.1477C>T
single nucleotide variant
 p.Arg493Ter Pathogenic/Likely pathogenic ★★☆☆ Familial hemiplegic migraine
c.1639del
Deletion
 p.Glu547fs Pathogenic ★★☆☆ Familial hemiplegic migraine
c.1642C>T
single nucleotide variant
 p.Arg548Cys Pathogenic ★★☆☆ Familial hemiplegic migraine
c.1810C>T
single nucleotide variant
 p.Arg604Ter Pathogenic ★★☆☆ Familial hemiplegic migraine
c.1843G>A
single nucleotide variant
 p.Gly615Arg Pathogenic/Likely pathogenic ★★☆☆ Familial hemiplegic migraine
c.2501G>A
single nucleotide variant
 p.Arg834Gln Pathogenic ★★☆☆ Familial hemiplegic migraine
c.2723G>A
single nucleotide variant
 p.Arg908Gln Pathogenic/Likely pathogenic ★★☆☆ Developmental and epileptic encephalopathy 98
c.3027T>A
single nucleotide variant
 p.Tyr1009Ter Pathogenic/Likely pathogenic ★★☆☆ Familial hemiplegic migraine

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Genetic changes in the ATP1A2 gene are associated with several inherited neurological disorders. These conditions often involve disturbances in brain function due to impaired ion balance and neurotransmitter regulation. Key conditions linked to ATP1A2 include alternating hemiplegia of childhood, and familial hemiplegic migraine type 2 (FHM2), which is a form of Migraine. Sporadic hemiplegic migraine, with similar symptoms to FHM2 but no family history, can also be caused by ATP1A2 variants.

  • Migraine
    Neurogenetics
    Polygenic / Complex
    Dedicated page coming soon

UK clinical status

The ATP1A2 gene is recognised in the UK's NHS Genomic Medicine Service, featuring on several NHS England National Genomic Test Directory panels. It is listed with a 'green' status for conditions such as Arthrogryposis, Brain channelopathy, and Dystonia, chorea or related movement disorder (both adult and childhood onset). Other panels include Early onset or syndromic epilepsy, Foetal anomalies, Hereditary ataxia (adult onset), Intellectual disability, Malformations of cortical development, Paroxysmal central nervous system disorders, Severe microcephaly, and Skeletal Muscle Channelopathies, all indicating its clinical significance.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arthrogryposis · R83 NHS GMS → Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Fetal anomalies · R21 NHS GMS → Paroxysmal central nervous system disorders · R66 NHS GMS → Severe microcephaly · R88 NHS GMS → DDG2P NHS GMS → Dystonia, chorea or related movement disorder, adult onset NHS GMS → Early onset or syndromic epilepsy NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the ATP1A2 gene?

The ATP1A2 gene provides instructions for the alpha-2 subunit of the Na+/K+ ATPase pump. This pump is crucial for moving sodium ions out of cells and potassium ions into cells, maintaining the electrical balance necessary for nerve cell communication, especially in glial cells.

What health conditions are associated with ATP1A2 gene variants?

Variants in the ATP1A2 gene are linked to several neurological conditions, including alternating hemiplegia of childhood, familial hemiplegic migraine type 2, and sporadic hemiplegic migraine. These conditions typically involve disruptions in brain function due to altered ion transport.

Where is the ATP1A2 gene located in the human genome?

The ATP1A2 gene is located on chromosome 1, specifically at position 1q23.2. This refers to a particular region on the long arm of chromosome 1.

References

  1. Riant F, Ducros A, Ploton C. De novo mutations in ATP1A2 and CACNA1A are frequent in early-onset sporadic hemiplegic migraine. Neurology. 2010. PMID: 20837964
  2. Tavraz NN, Dürr KL, Koenderink JB. Impaired plasma membrane targeting or protein stability by certain ATP1A2 mutations identified in sporadic or familial hemiplegic migraine. Channels (Austin, Tex.). 2009. PMID: 19372756
  3. Castro MJ, Nunes B, de Vries B. Two novel functional mutations in the Na+,K+-ATPase alpha2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes. Clinical genetics. 2008. PMID: 18028456
  4. Pietrobon D. Familial hemiplegic migraine. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2007. PMID: 17395138
  5. de Vries B, Freilinger T, Vanmolkot KR. Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine. Neurology. 2007. PMID: 18056581
  6. Riant F, De Fusco M, Aridon P. ATP1A2 mutations in 11 families with familial hemiplegic migraine. Human mutation. 2005. PMID: 16088919
  7. Jurkat-Rott K, Freilinger T, Dreier JP. Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants. Neurology. 2004. PMID: 15159495
  8. Swoboda KJ, Kanavakis E, Xaidara A. Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Annals of neurology. 2004. PMID: 15174025
  9. Bassi MT, Bresolin N, Tonelli A. A novel mutation in the ATP1A2 gene causes alternating hemiplegia of childhood. Journal of medical genetics. 2004. PMID: 15286158
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .