TXNDC5

Chr 6

thioredoxin domain containing 5

Also known as: ENDOPDI, ERP46, HCC-2, HCC2, PDIA15, STRF8, UNQ364

NCBI Gene: 81567ENSG00000239264UniProt: Q8NBS9

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]

103
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TXNDC5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 83 VUS of 103 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.
1.24LOEUF
pLI 0.000
Z-score 0.65
OE 0.86 (0.61–1.24)
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.
-0.42Z-score
OE missense 1.08 (0.97–1.20)
244 obs / 226.4 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.0.86 (0.61–1.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.97–1.20)
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.0.95
0≤1.21.6
LoF obs/exp: 21 / 24.5Missense obs/exp: 244 / 226.4Syn Z: 0.39

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS83
Likely Benign4
Benign1
13
Pathogenic
2
Likely Pathogenic
83
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
2
0
2
VUS
0
83
0
0
83
Likely Benign
0
3
0
1
4
Benign
0
1
0
0
1
Total087151103

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

View in ClinVar →

Protein Context — Lollipop Plot

TXNDC5 · 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
Early plasma proteomic biomarkers and prediction model of acute respiratory distress syndrome after cardiopulmonary bypass: a prospective nested cohort study.
Wang Y et al.·Int J Surg
2023Cohort
The role and mechanism of TXNDC5 in cardio-oncology: Killing two birds with one stone?
An N et al.·Curr Probl Cardiol
2025Review
CXCL10 and TRAIL Are Upregulated by TXNDC5 in Rheumatoid Arthritis Fibroblast-like Synoviocytes.
Xu B et al.·J Rheumatol
2018
The role of TXNDC5 in castration-resistant prostate cancer-involvement of androgen receptor signaling pathway.
Wang L et al.·Oncogene
2015
TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling.
Wang L et al.·Cell Mol Immunol
2018
Investigate pathogenic mechanism of TXNDC5 in rheumatoid arthritis.
Wang L et al.·PLoS One
2013Functional
Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis.
Chang X et al.·Arthritis Res Ther
2011
Investigating a pathogenic role for TXNDC5 in tumors.
Chang X et al.·Int J Oncol
2013
Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis.
Kocatürk B·Cancer Med
2023
Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation.
Robles J et al.·PLoS Comput Biol
2024Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor-Associated Macrophage-Mediated Prostate Cancer Metastasis.
Hu C et al.·Adv Sci (Weinh)
2026🔓 Open Access
Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5.
Wang Y et al.·J Adv Res
2025
ALKBH5-mediated m6A demethylation of TXNDC5 drives malignant progression in gastric cancer.
Peng W et al.·Epigenomics
2026🔓 Open Access
[Mechanism of Buyang Huanwu Decoction and Didang Decoction in treatment of chronic kidney disease based on ATF6/TXNDC5-regulated "macrophage-myofibroblast transformation" pathway].
Fan LF et al.·Zhongguo Zhong Yao Za Zhi
2025Functional
CXCL1 Promotes Fibrotic Remodeling in Atrial Fibrillation via Activation of TXNDC5 and Endoplasmic Reticulum Stress.
Yin R et al.·Cardiovasc Ther
2025🔓 Open AccessFunctional
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