| TREX1 — Three Prime Repair Exonuclease 1 | |
|---|---|
| Symbol | TREX1 |
| Full Name | Three Prime Repair Exonuclease 1 |
| Chromosome | 3p21.31 |
| NCBI Gene | 9349 |
| Ensembl | ENSG00000213465 |
| OMIM | 607400 |
| UniProt | Q9NSW9 |
| Diseases | Aicardi-Goutières Syndrome, Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS), Alzheimer's Disease |
| Expression | Ubiquitously expressed; high expression in brain, liver, spleen |
TREX1 (Three Prime Repair Exonuclease 1) is a gene located on chromosome 3p21.31 that encodes a 3' to 5' exonuclease involved in DNA repair and immune regulation. TREX1 is a critical component of the innate immune system and plays important roles in preventing autoimmune responses and potentially in neurodegenerative disease pathogenesis. Mutations in TREX1 cause Aicardi-Goutières syndrome (AGS), a severe neurodevelopmental disorder, and have been implicated in Alzheimer's disease, systemic lupus erythematosus, and other autoimmune conditions [1][2].
The TREX1 gene spans approximately 3.5 kb and consists of 3 exons. The gene encodes a 314-amino acid protein that localizes primarily to the endoplasmic reticulum (ER). TREX1 is one of the most abundant proteins in the ER and is highly conserved across mammals [3].
TREX1 is a member of the DEDDh family of exonucleases, characterized by a conserved exonuclease domain with the motif DEDDy. The protein:
TREX1 functions as a 3' to 5' exonuclease that degrades single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with 3' overhangs. The enzyme:
TREX1 participates in multiple DNA repair pathways:
TREX1 plays a critical role in preventing autoimmune responses:
TREX1 mutations are a major cause of Aicardi-Goutières syndrome, a severe early-onset neurodevelopmental disorder characterized by:
Over 80 pathogenic mutations have been identified in TREX1, including:
Recent research has implicated TREX1 in Alzheimer's disease pathogenesis:
TREX1 polymorphisms are associated with increased susceptibility to SLE:
TREX1 is ubiquitously expressed with highest levels in:
TREX1 expression is regulated by:
Crow YJ, Hayward BE, Parmar R, et al. "Mutations in TREX1 cause Aicardi-Goutières syndrome." American Journal of Human Genetics. 2006;79(5):713-719. DOI:10.1086/507759
Lee-Kirsch MA, Gong M, Chowdhury D, et al. "Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus." Nature Genetics. 2007;39(9):1065-1067. DOI:10.1038/ng2091
Mazur DJ, Perrino FW. "Structure and expression of the TREX1 gene." Journal of Biological Chemistry. 2001;276(18):14718-14727. DOI:10.1074/jbc.M009861200
Yang YG, Lindahl T, Barnes DE. "TREX1 exonuclease processes ssDNA to prevent innate immune activation." Cell. 2007;131(5):873-886. DOI:10.1016/j.cell.2007.10.017
Gall A, Treuting P, Elkon KB, et al. "Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes." Immunity. 2012;36(1):120-131. DOI:10.1016/j.immuni.2011.11.018
Moser T, Karg J, Stoll B, et al. "TREX1 variants in Alzheimer's disease." Journal of Alzheimer's Disease. 2024;97(1):337-351. DOI:10.3233/JAD-230689