TREX1

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title: "TREX1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/TREX1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.

Function

This gene encodes the major 3'-5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase. It is also a component of the SET complex, and acts to rapidly degrade 3' ends of nicked DNA during granzyme A-mediated cell death. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, RVCL (Retinal Vasculopathy with Cerebral Leukodystrophy), and Cree encephalitis. Multiple transcript variants encoding different isoforms have been found for this gene.

Clinical relevance

Mutations within the TREX1 gene cause familial chilblain lupus. The TREX1 polymorphisms confer susceptibility to systemic lupus erythematosus. Missense mutations of the TREX1 gene significantly downregulate its exonucleolytic capacity and result in the accumulation of nucleic acids. The build-up of the nucleic acids within the cytoplasm stimulates type-I interferon responses that could trigger autoimmune responses. The region containing the TREX1 gene (3p21.31) has been linked to COVID-19 severity in a recent genome-wide association study. This might explain the occurrence of chilblain like lesions in patients infected with SARS-CoV-2.

TREX1 helps HIV‑1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm

Mutations in TREX1 can give cause failure to appropriately remove ribonucleotides misincorporated into DNA. The removal process is ordinary performed by ribonucleotide excision repair. In humans, a defect in this process can give rise to Aicardi-Goutieres syndrome involving microcephaly and neuroinflammation.

Homology directed DNA repair

TREX1 is the most abundant 3’-5’ DNA exonuclease in mammals. Dominant C-terminal TREX1 genetic variants can disrupt homology-directed DNA repair and thus can trigger DNA damage and premature senescence phenotypes in humans, mice and Drosophila. Such TREX1 variants can also cause adult onset small vessel disease known as vasculopathy with cerebral leukoencephalopathy.

References

References

1. (Aug 1999). "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'→5' exonucleases". J Biol Chem.
2. (Aug 1999). "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein". EMBO J.
3. (Jul 2006). "Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus". Nat Genet.
4. "Entrez Gene: TREX1 three prime repair exonuclease 1".
5. (2021). "Overlap between Genetic Susceptibility to COVID-19 and Skin Diseases". Immunological Investigations.
6. (2020). "Genomewide Association Study of Severe Covid-19 with Respiratory Failure". New England Journal of Medicine.
7. (27 April 2015). "HIV-1 and interferons: who's interfering with whom?". Nature Reviews Microbiology.
8. (June 2017). "Genome integrity and disease prevention in the nervous system". Genes Dev.
9. (June 2024). "Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans". Nat Commun.

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::