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SETX gene


Normal Function

The SETX gene provides instructions for making a protein called senataxin. Senataxin is produced in a wide range of tissues, including the brain, spinal cord, and muscles. Based on the structure of senataxin, researchers believe that it is one of a class of proteins called helicases, which attach to particular regions of DNA or RNA (a chemical cousin of DNA) and temporarily unwind the strands of the molecule. By unwinding the strands, helicases allow other proteins to reach the strands to perform their function. Although senataxin's role in cells is not completely understood, it appears to be involved in the production of proteins from genes (transcription), the processing of RNA molecules, and the repair of damaged DNA.

Health Conditions Related to Genetic Changes

Amyotrophic lateral sclerosis

MedlinePlus Genetics provides information about Amyotrophic lateral sclerosis

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Ataxia with oculomotor apraxia

At least 125 mutations in the SETX gene have been found to cause ataxia with oculomotor apraxia type 2. This condition is characterized by difficulty coordinating movements (ataxia) and problems with side-to-side movements of the eyes (oculomotor apraxia). Most mutations replace single protein building blocks (amino acids) in senataxin. The mutations associated with ataxia with oculomotor apraxia type 2 are thought to disrupt the helicase function of senataxin. Although it is unclear how impaired senataxin function leads to the signs and symptoms of ataxia with oculomotor apraxia type 2, some researchers suggest that it disrupts DNA repair and can lead to an accumulation of DNA damage in cells. This accumulation can lead to cell death and seems particularly harmful to cells in the part of the brain involved in coordinating movements (the cerebellum), causing the characteristic movement problems of ataxia with oculomotor apraxia type 2.

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Charcot-Marie-Tooth disease

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease

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Other Names for This Gene

  • ALS4
  • AOA2
  • KIAA0625
  • SCAR1
  • Sen1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Becherel OJ, Yeo AJ, Stellati A, Heng EY, Luff J, Suraweera AM, Woods R, Fleming J, Carrie D, McKinney K, Xu X, Deng C, Lavin MF. Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing. PLoS Genet. 2013 Apr;9(4):e1003435. doi: 10.1371/journal.pgen.1003435. Epub 2013 Apr 11. Citation on PubMed or Free article on PubMed Central
  • Bennett CL, La Spada AR. Unwinding the role of senataxin in neurodegeneration. Discov Med. 2015 Feb;19(103):127-36. Citation on PubMed
  • Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet. 2004 Jun;74(6):1128-35. doi: 10.1086/421054. Epub 2004 Apr 21. Citation on PubMed or Free article on PubMed Central
  • Ferraiuolo L, Kirby J, Grierson AJ, Sendtner M, Shaw PJ. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Nov;7(11):616-30. doi: 10.1038/nrneurol.2011.152. Citation on PubMed
  • Fogel BL, Perlman S. Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. Neurology. 2006 Dec 12;67(11):2083-4. doi: 10.1212/01.wnl.0000247661.19601.28. No abstract available. Citation on PubMed
  • Groh M, Albulescu LO, Cristini A, Gromak N. Senataxin: Genome Guardian at the Interface of Transcription and Neurodegeneration. J Mol Biol. 2017 Oct 27;429(21):3181-3195. doi: 10.1016/j.jmb.2016.10.021. Epub 2016 Oct 19. Citation on PubMed
  • Le Ber I, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A, Chamayou C, Goizet C, Moreira MC, Klur S, Yahyaoui M, Agid Y, Koenig M, Stevanin G, Brice A, Durr A. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain. 2004 Apr;127(Pt 4):759-67. doi: 10.1093/brain/awh080. Epub 2004 Jan 21. Citation on PubMed
  • Moreira MC, Klur S, Watanabe M, Nemeth AH, Le Ber I, Moniz JC, Tranchant C, Aubourg P, Tazir M, Schols L, Pandolfo M, Schulz JB, Pouget J, Calvas P, Shizuka-Ikeda M, Shoji M, Tanaka M, Izatt L, Shaw CE, M'Zahem A, Dunne E, Bomont P, Benhassine T, Bouslam N, Stevanin G, Brice A, Guimaraes J, Mendonca P, Barbot C, Coutinho P, Sequeiros J, Durr A, Warter JM, Koenig M. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet. 2004 Mar;36(3):225-7. doi: 10.1038/ng1303. Epub 2004 Feb 8. Citation on PubMed
  • Nanetti L, Cavalieri S, Pensato V, Erbetta A, Pareyson D, Panzeri M, Zorzi G, Antozzi C, Moroni I, Gellera C, Brusco A, Mariotti C. SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein. Orphanet J Rare Dis. 2013 Aug 14;8:123. doi: 10.1186/1750-1172-8-123. Citation on PubMed or Free article on PubMed Central
  • Suraweera A, Becherel OJ, Chen P, Rundle N, Woods R, Nakamura J, Gatei M, Criscuolo C, Filla A, Chessa L, Fusser M, Epe B, Gueven N, Lavin MF. Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage. J Cell Biol. 2007 Jun 18;177(6):969-79. doi: 10.1083/jcb.200701042. Epub 2007 Jun 11. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.