TXN2

Chr 22AR

thioredoxin 2

Also known as: COXPD29, MT-TRX, MTRX, TRX2, TXN

NCBI Gene: 25828ENSG00000100348UniProt: Q99757

This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 29MIM #616811
AR
111
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TXN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 57 VUS of 111 total submissions

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.
1.73LOEUF
pLI 0.000
Z-score 0.05
OE 0.98 (0.55–1.73)
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.
0.61Z-score
OE missense 0.82 (0.69–0.99)
79 obs / 95.9 exp
Tolerant

Mild missense constraint

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.0.98 (0.55–1.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.69–0.99)
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.1.13
0≤1.21.6
LoF obs/exp: 7 / 7.1Missense obs/exp: 79 / 95.9Syn Z: -0.62

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS57
Likely Benign23
Benign7
16
Pathogenic
1
Likely Pathogenic
57
VUS
23
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
2
35
20
0
57
Likely Benign
0
1
5
17
23
Benign
0
0
6
1
7
Total2364818104

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TXN2 · 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
THIOREDOXIN 2; TXN2
MIM #609063 · *

?Combined oxidative phosphorylation deficiency 29

MIM #616811

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The interplay between metabolic reprogramming, mitochondrial impairment, and steroid response in proliferative vitreoretinopathy.
Huang X et al.·Free Radic Biol Med
2025
Regular aspirin intake and prognosis of TxN2-3M0 nasopharyngeal carcinoma: A cohort study based on propensity score matching.
Chang H et al.·Oral Oncol
2020Cohort
Germline Polymorphisms in Genes Involved in the Antioxidant System Predict the Efficacy of Cetuximab in Metastatic Colorectal Cancer Patients Enrolled in FIRE-3 Trial.
Arai H et al.·Clin Colorectal Cancer
2022Clinical trial
Psychological, clinical and pathological effects of relaxation training and guided imagery during primary chemotherapy.
Walker LG et al.·Br J Cancer
1999Clinical trial
Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration.
Holzerova E et al.·Brain
2016Case report
Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.
Hughes DJ et al.·Free Radic Biol Med
2023Cohort
Effects of long-term low oxygen tension in human chondrosarcoma cells.
Piltti J et al.·J Cell Biochem
2018
Current and potential chemotherapeutic agents used for induction chemotherapy in the treatment of breast cancer.
Smith IC et al.·Curr Pharm Des
2000Review
Mechanism of KAT2A regulation of H3K36ac in manganese-induced oxidative damage to mitochondria in the nervous system and intervention by curcumin.
Liu Y et al.·Ecotoxicol Environ Saf
2024Functional
Association between genetic variants in oxidative stress-related genes and osteoporotic bone fracture. The Hortega follow-up study.
Usategui-Martín R et al.·Gene
2022Natural history
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