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Genetics Home Reference: your guide to understanding genetic conditions
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ATP1A3

Reviewed February 2014

What is the official name of the ATP1A3 gene?

The official name of this gene is “ATPase, Na+/K+ transporting, alpha 3 polypeptide.”

ATP1A3 is the gene's official symbol. The ATP1A3 gene is also known by other names, listed below.

What is the normal function of the ATP1A3 gene?

The ATP1A3 gene provides instructions for making one part (the alpha-3 subunit) of a protein known as Na+/K+ ATPase or the sodium pump. This protein uses energy from a molecule called adenosine triphosphate (ATP) to transport charged atoms (ions) into and out of cells. Specifically, it pumps sodium ions (Na+) out of cells and potassium ions (K+) into cells.

Na+/K+ ATPases that include the alpha-3 subunit are primarily found in nerve cells (neurons) in the brain and are critical for their normal function. The movement of sodium and potassium ions helps regulate the electrical activity of these cells and plays an important role in the signaling process that controls muscle movement. The activity of Na+/K+ ATPase also helps regulate cell size (volume).

Additionally, Na+/K+ ATPase helps regulate a process called neurotransmitter reuptake. Neurotransmitters are chemicals that transmit signals from one neuron to another. After a neurotransmitter has had its effect, it must be removed quickly from the space between the neurons. The reuptake of neurotransmitters is carefully controlled to ensure that signals are sent and received accurately throughout the nervous system.

Does the ATP1A3 gene share characteristics with other genes?

The ATP1A3 gene belongs to a family of genes called ATP (ATPase superfamily).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the ATP1A3 gene related to health conditions?

alternating hemiplegia of childhood - caused by mutations in the ATP1A3 gene

Mutations in the ATP1A3 gene are the primary cause of a neurological condition called alternating hemiplegia of childhood; at least 25 ATP1A3 gene mutations have been found in affected individuals. This condition is characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side to the other or affects both sides of the body at the same time.

Most ATP1A3 gene mutations associated with alternating hemiplegia of childhood change single protein building blocks (amino acids) in the alpha-3 subunit of Na+/K+ ATPase. These genetic changes appear to impair the pump's ability to transport ions, although it is unclear how the mutations lead to the specific features of alternating hemiplegia of childhood.

rapid-onset dystonia parkinsonism - caused by mutations in the ATP1A3 gene

At least nine mutations in the ATP1A3 gene have been identified in individuals and families with rapid-onset dystonia parkinsonism. Most of these mutations change single amino acids in the alpha-3 subunit of Na+/K+ ATPase. Changes in the protein's structure can reduce its activity or make it unstable. Studies suggest that the defective Na+/K+ ATPase is unable to transport sodium ions normally, which disrupts the electrical activity of neurons in the brain. However, it is unclear how a malfunctioning Na+/K+ ATPase causes the movement abnormalities characteristic of rapid-onset dystonia parkinsonism.

Where is the ATP1A3 gene located?

Cytogenetic Location: 19q13.31

Molecular Location on chromosome 19: base pairs 41,966,475 to 41,994,275

The ATP1A3 gene is located on the long (q) arm of chromosome 19 at position 13.31.

The ATP1A3 gene is located on the long (q) arm of chromosome 19 at position 13.31.

More precisely, the ATP1A3 gene is located from base pair 41,966,475 to base pair 41,994,275 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ATP1A3?

You and your healthcare professional may find the following resources about ATP1A3 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ATP1A3 gene or gene products?

  • AT1A3_HUMAN
  • DYT12
  • MGC13276
  • Na+/K+ ATPase 3
  • Na+/K+ -ATPase alpha 3 subunit
  • RDP
  • sodium-potassium-ATPase, alpha 3 polypeptide
  • sodium/potassium-transporting ATPase alpha-3 chain
  • sodium pump 3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ATP1A3?

acids ; adenosine triphosphate ; ATP ; calcium ; cell ; dystonia ; gene ; hemiplegia ; ions ; molecule ; Na ; nervous system ; neurological ; neuron ; neurotransmitters ; parkinsonism ; potassium ; protein ; sodium ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Blanco-Arias P, Einholm AP, Mamsa H, Concheiro C, Gutiérrez-de-Terán H, Romero J, Toustrup-Jensen MS, Carracedo A, Jen JC, Vilsen B, Sobrido MJ. A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism. Hum Mol Genet. 2009 Jul 1;18(13):2370-7. doi: 10.1093/hmg/ddp170. Epub 2009 Apr 7. (http://www.ncbi.nlm.nih.gov/pubmed/19351654?dopt=Abstract)
  • Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Münchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Ozelius LJ. The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. Brain. 2007 Mar;130(Pt 3):828-35. Epub 2007 Feb 4. (http://www.ncbi.nlm.nih.gov/pubmed/17282997?dopt=Abstract)
  • de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ. Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron. 2004 Jul 22;43(2):169-75. (http://www.ncbi.nlm.nih.gov/pubmed/15260953?dopt=Abstract)
  • Gene Review: Rapid-Onset Dystonia-Parkinsonism (http://www.ncbi.nlm.nih.gov/books/NBK1115/)
  • Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E; European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium; Biobanca e Registro Clinico per l'Emiplegia Alternante (I.B.AHC) Consortium; European Network for Research on Alternating Hemiplegia (ENRAH) for Small and Medium-sized Enterpriese (SMEs) Consortium, Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L, Huff C, Jorde LB, Reyna SP, Murphy KJ, Shianna KV, Gumbs CE, Little L, Silver K, Ptáček LJ, Haan J, Ferrari MD, Bye AM, Herkes GK, Whitelaw CM, Webb D, Lynch BJ, Uldall P, King MD, Scheffer IE, Neri G, Arzimanoglou A, van den Maagdenberg AM, Sisodiya SM, Mikati MA, Goldstein DB. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012 Sep;44(9):1030-4. doi: 10.1038/ng.2358. Epub 2012 Jul 29. (http://www.ncbi.nlm.nih.gov/pubmed/22842232?dopt=Abstract)
  • Kamm C, Fogel W, Wächter T, Schweitzer K, Berg D, Kruger R, Freudenstein D, Gasser T. Novel ATP1A3 mutation in a sporadic RDP patient with minimal benefit from deep brain stimulation. Neurology. 2008 Apr 15;70(16 Pt 2):1501-3. doi: 10.1212/01.wnl.0000310431.41036.e0. (http://www.ncbi.nlm.nih.gov/pubmed/18413579?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/478)
  • Rodacker V, Toustrup-Jensen M, Vilsen B. Mutations Phe785Leu and Thr618Met in Na+,K+-ATPase, associated with familial rapid-onset dystonia parkinsonism, interfere with Na+ interaction by distinct mechanisms. J Biol Chem. 2006 Jul 7;281(27):18539-48. Epub 2006 Apr 21. (http://www.ncbi.nlm.nih.gov/pubmed/16632466?dopt=Abstract)
  • Rosewich H, Thiele H, Ohlenbusch A, Maschke U, Altmüller J, Frommolt P, Zirn B, Ebinger F, Siemes H, Nürnberg P, Brockmann K, Gärtner J. Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. Lancet Neurol. 2012 Sep;11(9):764-73. doi: 10.1016/S1474-4422(12)70182-5. Epub 2012 Jul 30. (http://www.ncbi.nlm.nih.gov/pubmed/22850527?dopt=Abstract)
  • Zanotti-Fregonara P, Vidailhet M, Kas A, Ozelius LJ, Clot F, Hindié E, Ravasi L, Devaux JY, Roze E. [123I]-FP-CIT and [99mTc]-HMPAO single photon emission computed tomography in a new sporadic case of rapid-onset dystonia-parkinsonism. J Neurol Sci. 2008 Oct 15;273(1-2):148-51. doi: 10.1016/j.jns.2008.06.033. Epub 2008 Aug 3. (http://www.ncbi.nlm.nih.gov/pubmed/18675996?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2014
Published: July 14, 2014