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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TXNL1
thioredoxin like 1
Chromosome 18 · 18q21.31
NCBI Gene: 9352Ensembl: ENSG00000091164.14HGNC: HGNC:12436UniProt: O43396
113PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
disulfide oxidoreductase activitycytosolcytoplasmprotein-disulfide reductase activitymood disorderulcerative colitisFuchs' endothelial dystrophycorneal disease
✦AI Summary

TXNL1 (thioredoxin like 1) is a cytoplasmic thioredoxin-fold protein with dual functions as both a redox-active enzyme and an ATP-independent chaperone 1. As a redox enzyme, TXNL1 exhibits thioredoxin activity with a redox potential of approximately -250 mV, capable of reducing disulfides in insulin, cystine, and glutathione disulfide through NADPH-dependent reactions coupled to thioredoxin reductase, though with lower catalytic efficiency than classical thioredoxin 12. Additionally, TXNL1 functions as a redox-active cofactor of the 26S proteasome, binding to the Rpn11 subunit and facilitating protein degradation through the ubiquitin-proteasome pathway 23. The protein also demonstrates chaperone activity independent of its redox function, preventing protein aggregation without requiring ATP or redox activity 1. TXNL1 plays critical roles in cellular stress responses and disease pathogenesis. Arsenic exposure specifically downregulates TXNL1 expression, promoting ROS-mediated malignant transformation in bronchial epithelial cells 4. In cancer, TXNL1 regulates cisplatin resistance through modulation of DNA repair protein XRCC1 5, while in cardiovascular disease, TXNL1 is involved in acute myocardial infarction through PANoptosis mechanisms 6. These findings establish TXNL1 as a multifunctional protein linking oxidative stress regulation, protein quality control, and disease pathogenesis.

Sources cited
1
TXNL1 has dual functions as redox-active thioredoxin and ATP-independent chaperone with specific catalytic properties
PMID: 37804695
2
TXNL1 functions as redox-active cofactor of 26S proteasome with -250 mV redox potential
PMID: 19349277
3
TXNL1 binds proteasome via interactions with PSMD1, PSMD4, and PSMD14 subunits
PMID: 40770113
4
Arsenic specifically downregulates TXNL1 expression promoting ROS-mediated malignant transformation
PMID: 41275040
5
TXNL1 regulates cisplatin resistance through XRCC1 pathway in gastric cancer
PMID: 24525731
6
TXNL1 involvement in acute myocardial infarction through PANoptosis mechanisms
PMID: 40114419
Disease Associationsⓘ20
mood disorderOpen Targets
0.31Weak
ulcerative colitisOpen Targets
0.29Weak
Fuchs' endothelial dystrophyOpen Targets
0.25Weak
corneal diseaseOpen Targets
0.25Weak
corneal dystrophyOpen Targets
0.24Weak
corneal edemaOpen Targets
0.23Weak
schizophreniaOpen Targets
0.22Weak
hypertrophic cardiomyopathyOpen Targets
0.21Weak
cornea transplantationOpen Targets
0.20Weak
ovarian dysfunctionOpen Targets
0.17Weak
musculoskeletal system diseaseOpen Targets
0.16Weak
smoking initiationOpen Targets
0.13Weak
cataractOpen Targets
0.13Weak
brain aneurysmOpen Targets
0.13Weak
sinusitisOpen Targets
0.13Weak
polyarteritis nodosaOpen Targets
0.13Weak
lymphatic system diseaseOpen Targets
0.13Weak
Varicose veinsOpen Targets
0.13Weak
vein disorderOpen Targets
0.13Weak
diabetic ketoacidosisOpen Targets
0.12Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PSMD14Protein interaction99%PSMD4Protein interaction92%TP53I11Protein interaction77%NFU1Protein interaction77%DAZAP2Protein interaction76%COPS5Protein interaction76%
Tissue Expression6 tissues
Brain
100%
Heart
63%
Bone Marrow
62%
Liver
47%
Ovary
37%
Lung
33%
Gene Interaction Network
Click a node to explore
TXNL1PSMD14PSMD4TP53I11NFU1DAZAP2COPS5
PROTEIN STRUCTURE
Preparing viewer…
PDB1GH2 · 2.22 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.68LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.43 [0.28–0.68]
RankingsWhere TXNL1 stands among ~20K protein-coding genes
  • #4,210of 20,598
    Most Researched113 · top quartile
  • #5,018of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedTXNL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Thioredoxin-interacting protein links oxidative stress to inflammasome activation.
PMID: 20023662
Nat Immunol · 2010
1.00
2
Structure of the TXNL1-bound proteasome.
PMID: 40770113
Nat Struct Mol Biol · 2025
0.90
3
The role of TXNL1 in disease: treatment strategies for cancer and diseases with oxidative stress.
PMID: 33660093
Mol Biol Rep · 2021
0.80
4
TXNL1-XRCC1 pathway regulates cisplatin-induced cell death and contributes to resistance in human gastric cancer.
PMID: 24525731
Cell Death Dis · 2014
0.70
5
Arsenic promotes ROS-mediated malignant transformation of bronchial epithelial cells by specifically downregulating TXNL1 expression.
PMID: 41275040
Commun Biol · 2025
0.60