URL of this page: https://medlineplus.gov/genetics/gene/trex1/

TREX1 gene

three prime repair exonuclease 1
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Normal Function

The TREX1 gene provides instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means that it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during copying (replication) of cells' genetic material in preparation for cell division. These fragments may also be generated during DNA repair, cell death (apoptosis), and other processes.

Health Conditions Related to Genetic Changes

Aicardi-Goutières syndrome

At least 82 mutations in the TREX1 gene have been identified in people with Aicardi-Goutières syndrome, a disorder that involves severe brain dysfunction (encephalopathy), skin lesions, and other health problems. Most of these mutations are believed to prevent the production of the 3-prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme results in an accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules may be mistaken by cells for the genetic material of viral invaders, triggering immune system reactions that damage the brain, skin, and other organs and systems and result in the signs and symptoms of Aicardi-Goutières syndrome.

More About This Health Condition

Systemic lupus erythematosus

MedlinePlus Genetics provides information about Systemic lupus erythematosus

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Other disorders

Mutations in the TREX1 gene have also been identified in people with other disorders involving the immune system. These disorders include a chronic inflammatory disease called systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin. Features of SLE, especially chilblain lupus, often also occur in people with Aicardi-Goutières syndrome (described above).

TREX1 gene mutations have also been found in people with a disorder called autosomal dominant retinal vasculopathy with cerebral leukodystrophy, which affects the brain and the blood vessels in the specialized light-sensitive tissue that lines the back of the eye (the retina).

As in Aicardi-Goutières syndrome, absence or impaired function of the 3-prime repair exonuclease 1 enzyme may cause immune system dysfunction that damages the brain, skin, blood vessels, and other parts of the body. It is not clear why mutations in the same gene cause several different disorders.

Other Names for This Gene

  • 3' repair exonuclease 1
  • 3'-5' exonuclease TREX1
  • AGS1
  • CRV
  • deoxyribonuclease III, dnaQ/mutD-like
  • DKFZp434J0310
  • DNase III
  • DRN3
  • HERNS
  • three prime repair exonuclease 1 isoform a
  • three prime repair exonuclease 1 isoform b
  • TREX1_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Research Resources

References

  • Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, Oojageer A, Anderson B, Pizzino A, Helman G, Abdel-Hamid MS, Abdel-Salam GM, Ackroyd S, Aeby A, Agosta G, Albin C, Allon-Shalev S, Arellano M, Ariaudo G, Aswani V, Babul-Hirji R, Baildam EM, Bahi-Buisson N, Bailey KM, Barnerias C, Barth M, Battini R, Beresford MW, Bernard G, Bianchi M, Billette de Villemeur T, Blair EM, Bloom M, Burlina AB, Carpanelli ML, Carvalho DR, Castro-Gago M, Cavallini A, Cereda C, Chandler KE, Chitayat DA, Collins AE, Sierra Corcoles C, Cordeiro NJ, Crichiutti G, Dabydeen L, Dale RC, D'Arrigo S, De Goede CG, De Laet C, De Waele LM, Denzler I, Desguerre I, Devriendt K, Di Rocco M, Fahey MC, Fazzi E, Ferrie CD, Figueiredo A, Gener B, Goizet C, Gowrinathan NR, Gowrishankar K, Hanrahan D, Isidor B, Kara B, Khan N, King MD, Kirk EP, Kumar R, Lagae L, Landrieu P, Lauffer H, Laugel V, La Piana R, Lim MJ, Lin JP, Linnankivi T, Mackay MT, Marom DR, Marques Lourenço C, McKee SA, Moroni I, Morton JE, Moutard ML, Murray K, Nabbout R, Nampoothiri S, Nunez-Enamorado N, Oades PJ, Olivieri I, Ostergaard JR, Pérez-Dueñas B, Prendiville JS, Ramesh V, Rasmussen M, Régal L, Ricci F, Rio M, Rodriguez D, Roubertie A, Salvatici E, Segers KA, Sinha GP, Soler D, Spiegel R, Stödberg TI, Straussberg R, Swoboda KJ, Suri M, Tacke U, Tan TY, te Water Naude J, Wee Teik K, Thomas MM, Till M, Tonduti D, Valente EM, Van Coster RN, van der Knaap MS, Vassallo G, Vijzelaar R, Vogt J, Wallace GB, Wassmer E, Webb HJ, Whitehouse WP, Whitney RN, Zaki MS, Zuberi SM, Livingston JH, Rozenberg F, Lebon P, Vanderver A, Orcesi S, Rice GI. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015 Feb;167A(2):296-312. doi: 10.1002/ajmg.a.36887. Epub 2015 Jan 16. Citation on PubMed or Free article on PubMed Central
  • Crow YJ, Rehwinkel J. Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum Mol Genet. 2009 Oct 15;18(R2):R130-6. doi: 10.1093/hmg/ddp293. Review. Citation on PubMed or Free article on PubMed Central
  • Crow YJ. Aicardi-Goutières Syndrome. 2005 Jun 29 [updated 2016 Nov 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1475/ Citation on PubMed
  • Crow YJ. Aicardi-Goutières syndrome. Handb Clin Neurol. 2013;113:1629-35. doi: 10.1016/B978-0-444-59565-2.00031-9. Review. Citation on PubMed
  • Cuadrado E, Michailidou I, van Bodegraven EJ, Jansen MH, Sluijs JA, Geerts D, Couraud PO, De Filippis L, Vescovi AL, Kuijpers TW, Hol EM. Phenotypic variation in Aicardi-Goutières syndrome explained by cell-specific IFN-stimulated gene response and cytokine release. J Immunol. 2015 Apr 15;194(8):3623-33. doi: 10.4049/jimmunol.1401334. Epub 2015 Mar 13. Citation on PubMed
  • Kavanagh D, Spitzer D, Kothari PH, Shaikh A, Liszewski MK, Richards A, Atkinson JP. New roles for the major human 3'-5' exonuclease TREX1 in human disease. Cell Cycle. 2008 Jun 15;7(12):1718-25. Epub 2008 Jun 16. Review. Citation on PubMed or Free article on PubMed Central
  • Lehtinen DA, Harvey S, Mulcahy MJ, Hollis T, Perrino FW. The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease. J Biol Chem. 2008 Nov 14;283(46):31649-56. doi: 10.1074/jbc.M806155200. Epub 2008 Sep 18. Citation on PubMed or Free article on PubMed Central
  • Lindahl T, Barnes DE, Yang YG, Robins P. Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease. Biochem Soc Trans. 2009 Jun;37(Pt 3):535-8. doi: 10.1042/BST0370535. Citation on PubMed
  • Livingston JH, Crow YJ. Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi-Goutières Syndrome and Beyond. Neuropediatrics. 2016 Dec;47(6):355-360. Epub 2016 Sep 19. Review. Citation on PubMed
  • Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, Robins P, Harvey S, Hollis T, O'Hara A, Herrick AL, Bowden AP, Perrino FW, Lindahl T, Barnes DE, Crow YJ. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am J Hum Genet. 2007 Apr;80(4):811-5. Epub 2007 Feb 19. Citation on PubMed or Free article on PubMed Central
  • Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D'Arrigo S, Dean J, De Laet C, De Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, Lim MJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, McClure JP, McWilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P, Crow YJ. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet. 2007 Oct;81(4):713-25. Epub 2007 Sep 4. Citation on PubMed or Free article on PubMed Central
  • Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, De Laet C, De Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W Jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013 Dec;12(12):1159-69. doi: 10.1016/S1474-4422(13)70258-8. Epub 2013 Oct 30. Citation on PubMed or Free article on PubMed Central
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