Alt. symbols: AGS1 | DRN3

Approved name: three prime repair exonuclease 1
Alt. names: Aicardi-Goutieres syndrome 1

Location: 3p21.31: 48465811 - 48467645 (+)
Gene type: protein_coding, 6 transcripts.

Scores: LoFtool: 0.174000 | pLI: 0.09334072 | LOEUF: 0.694

HGNC: 12269

NCBI: 11277, RefSeq: NG_009820.2

Ensembl: ENSG00000213689.14

LRG_282 | Status: public

OMIM: 606609

Expression | ProteinAtlas

TREX1 encodes a major cellular 3'-to-5' DNA exonuclease that acts on both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. This activity enables it to digest DNA fragments generated by endogenous retroelements (i.e. L1, LTR and SINE), preventing their accumulation in the cytosol and cell-intrinsic activation of IFN-driven innate immunity pathways. Similarly, its processing of aberrant DNA replication intermediates prevents chronic ATM-dependent checkpoint activation (PMID: 18045533).

Monoallelic and biallelic nonsense, missense, and frameshift mutations in TREX1, as well as small sub-exonic deletions and duplications, have been associated with classic AGS (Aicardi-Goutieres syndrome) [OMIM: 225750]. Some of these same variants have also been reported for other clinically overlapping conditions. For example, monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 have been associated with AD susceptibility to SLE [OMIM: 152700] and chilblain lupus [OMIM: 610448]. Other variants have been associated with Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) [MIM:192315], an adult-onset AD disorder involving brain microvasculature that leads to CNS degeneration with progressive loss of vision, strokes, motor impairment, cognitive decline, and systemic vascular involvement (i.e. hepatorenal disease) in a subset of patients (PMID: 17660820). [Load More]