TREX2

Chr X

three prime repair exonuclease 2

NCBI Gene: 11219ENSG00000183479UniProt: Q9BQ50

This gene encodes a nuclear protein with 3' to 5' exonuclease activity. The encoded protein participates in double-stranded DNA break repair, and may interact with DNA polymerase delta. [provided by RefSeq, Nov 2012]

0
ClinVar variants
0
Pathogenic / LP
0.45
pLI score
0
Active trials
Clinical Summary— TREX2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.54LOEUF
pLI 0.454
Z-score 1.15
OE 0.00 (0.00–1.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.66Z-score
OE missense 1.18 (1.02–1.37)
125 obs / 105.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.02–1.37)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.23
0≤1.21.6
LoF obs/exp: 0 / 1.5Missense obs/exp: 125 / 105.9Syn Z: -1.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TREX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TREX2 deficiency suppresses spontaneous and genotoxin-associated mutagenesis.
Marple T et al.·Cell Rep
2024
The Exonuclease Trex2 Shapes Psoriatic Phenotype.
Manils J et al.·J Invest Dermatol
2016
Measuring TREX1 and TREX2 exonuclease activities.
Hemphill WO et al.·Methods Enzymol
2019
TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A).
Ko JH et al.·Cell Rep
2020
Systematic high-throughput evaluation reveals FrCas9's superior specificity and efficiency for therapeutic genome editing.
Tian R et al.·Sci Adv
2025
Metabolic Regulation of cGAS-STING Signaling in the Tumor Microenvironment: Dual Immune Roles and Therapeutic Implications.
Wu Y et al.·Cytokine Growth Factor Rev
2025Review
Human TREX2 components PCID2 and centrin 2, but not ENY2, have distinct functions in protein export and co-localize to the centrosome.
Cunningham CN et al.·Exp Cell Res
2014
Psoriatic skin transcript phenotype: androgen/estrogen and cortisone/cortisol imbalance with increasing DNA damage response.
Başar Kılıç Ş et al.·Mol Biol Rep
2024
Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.
Quinting T et al.·Front Endocrinol (Lausanne)
2021
Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer.
Smith CG et al.·Hum Mutat
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools