ArticleNature communications2022
Structural basis of human TREX1 DNA degradation and autoimmune disease.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.Nature communications · 2026Pooled it
- PXL: a nucleic acid-binding module of the promyelocytic leukemia protein.Nucleic acids research · 2026Article
- Noncoding RNA TY1 reverses fibrosis in systemic sclerosis by attenuating the cGAS/STING pathway.JCI insight · 2026Article
- Structural and biochemical characterization of Grimontia hollisae thermostable direct hemolysin with DNA reveals first Vibrio hemolysin with nuclease activity.Nucleic acids research · 2026Article
- Extracellular Traps in Coronary Thrombus Aspirates from Patients with ST-Elevation Myocardial Infarction.International journal of molecular sciences · 2026Article
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- Rational design of carbazole-based STING inhibitors for treating cGAS-STING pathway-driven inflammatory disorders.Nature communications · 2026Article
- Fasting-mimicking diet induces IFNβ secretion in tumor-associated macrophages via NRF1-mediated ubiquitin-dependent proteolysis of Trex1.British journal of cancer · 2026Article
- PXL: a Nucleic Acid-Binding Module of Promyelocytic Leukemia Protein.bioRxiv : the preprint server for biology · 2026Article
- Disordered DNA-binding motif forms a modulation site for inhibiting the cancer immunotherapy target TREX1.Nucleic acids research · 2026Article
- cGAS-STING pathway in innate immunity and its cell-specific role in kidney diseases.Frontiers in immunology · 2026Review
- Gigaxonin Potentiates Antiviral Innate Immune Responses by Targeting cGAS and TREX1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Prevalence and impact of molecular variation in the three-prime repair exonuclease 1 TREX1 and its implications for oncology.Human genomics · 2025Article
- Carnosic Acid Directly Targets STING C-Terminal Tail to Improve STING-Mediated Inflammatory Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- The intersection of TREX1, cGAS, STING and the DNA damage theory of aging.Frontiers in aging · 2025Review
- Role of cGAS/STING pathway in aging and sexual dimorphism in diabetic kidney disease.JCI insight · 2024Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- Coordinated in confined migration: crosstalk between the nucleus and ion channel-mediated mechanosensation.Trends in cell biology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
TREX1 is a cytosolic DNA nuclease essential for regulation of cGAS-STING immune signaling. Existing structures of mouse TREX1 establish a mechanism of DNA degradation and provide a key model to explain autoimmune disease, but these structures incompletely explain human disease-associated mutations and have limited ability to guide development of small-molecule therapeutics. Here we determine crystal structures of human TREX1 in apo and DNA-bound conformations that provide high-resolution detail of all human-specific features. A 1.25 Å structure of human TREX1 establishes a complete model of solvation of the exonuclease active site and a 2.2 Å structure of the human TREX1-DNA complex enables identification of specific substitutions involved in DNA recognition. We map each TREX1 mutation associated with autoimmune disease and establish distinct categories of substitutions predicted to impact enzymatic function, protein stability, and interaction with cGAS-DNA liquid droplets. Our results explain how human-specific substitutions regulate TREX1 function and provide a foundation for structure-guided design of TREX1 therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.