TREX1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TREX1 gene, its protein product, associated diseases, and mutation spectrum.
Gene Information Card
| Symbol | TREX1 |
|---|---|
| Full Name | Three prime repair exonuclease 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 11277 ncbi.nlm.nih.gov/gene/11277 |
| Ensembl ID | ENSG00000137869 |
| UniProt ID | Q9NSU2 |
| OMIM ID | 606609 |
| HGNC ID | 12269 |
| Aliases | AGS1, CRV, DKFZp434J0310, FLJ12106, FLJ22051, MGC133267, ATRIP |
Description
TREX1 (Three prime repair exonuclease 1) encodes a 3'->5' DNA exonuclease that is the major DNA exonuclease in mammalian cells. It is involved in DNA replication, repair, and the clearance of cytosolic DNA to prevent immune activation. Mutations in TREX1 are associated with several autoimmune and inflammatory diseases, including Aicardi-Goutières syndrome, familial chilblain lupus, and systemic lupus erythematosus.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Aicardi-Goutières syndrome (AGS1) | Loss-of-function mutations lead to accumulation of cytosolic DNA, triggering chronic type I interferon response. | ClinVar, OMIM |
| Familial chilblain lupus | Dominant-negative mutations impair exonuclease activity, causing interferon-mediated inflammation. | OMIM, ClinVar |
| Systemic lupus erythematosus (SLE) | Heterozygous mutations with reduced enzyme activity contribute to immune dysregulation. | ClinVar, PubMed |
| Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) | C-terminal frameshift mutations cause retention in the ER, leading to angiopathy. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Spleen | 25.4 | Medium |
| Lymph node | 22.1 | Medium |
| Bone marrow | 18.7 | Low |
| Lung | 15.3 | Low |
| Liver | 12.9 | Low |
| Brain | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HeLa | 20.5 | Cervical carcinoma |
| HEK293 | 18.3 | Embryonic kidney |
| Jurkat | 15.7 | T-cell leukemia |
| HepG2 | 12.1 | Hepatocellular carcinoma |
| A549 | 10.4 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.Arg114His | Missense | Rare (0.01%) | Reduced exonuclease activity; associated with AGS1 |
| p.Asp18Asn | Missense | Rare | Loss of function; familial chilblain lupus |
| p.Val235del | Deletion | Rare | Dominant-negative; SLE |
| p.Leu287ValfsTer29 | Frameshift | Rare | C-terminal truncation; RVCL |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause Aicardi-Goutières syndrome due to complete absence of exonuclease activity, leading to cytosolic DNA accumulation and interferon activation.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may exhibit altered substrate specificity but not classic gain-of-function.
Dominant Negative (DN)
Heterozygous mutations, particularly in the catalytic domain, can exert dominant-negative effects by dimerizing with wild-type subunits, reducing overall enzyme activity and causing chilblain lupus or SLE.
View complete mutation data：
Gene Ontology (GO)
| • 3'-5' exonuclease activity | • DNA binding |
| • DNA repair | • DNA replication |
| • Cytosolic DNA sensing | • Immune response |
| • Nucleic acid phosphodiester bond hydrolysis |
Pathways
• DNA damage response
• Cytosolic DNA-sensing pathway
• Interferon signaling
• Base excision repair
Protein Summary
The TREX1 protein is a 369-amino acid exonuclease that exists as a homodimer. It localizes to the endoplasmic reticulum and cytosol, where it degrades single-stranded and double-stranded DNA. It plays a critical role in preventing autoimmune responses by clearing self-DNA from the cytosol. Defects in TREX1 lead to chronic type I interferon production, linking it to several autoinflammatory conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TREX1 Knockout HEK293 Cell Line | EDJ-KQ51063 | Human | 11277 | Details Get a Quote |
| TREX1 Knockout HeLa Cell Line | EDJ-KQ55622 | Human | 11277 | Details Get a Quote |
| TREX1 Knockout A-549 Cell Line | EDJ-KQ64121 | Human | 11277 | Details Get a Quote |
| TREX1 Knockout HCT 116 Cell Line | EDJ-KQ72565 | Human | 11277 | Details Get a Quote |
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