TXNDC12

Chr 1

thioredoxin domain containing 12

Also known as: AG1, AGR1, ERP16, ERP18, ERP19, PDIA16, TLP19, hAG-1

NCBI Gene: 51060ENSG00000117862UniProt: O95881

This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. This protein localizes to the endoplasmic reticulum and has a single atypical active motif. The encoded protein is mainly involved in catalyzing native disulfide bond formation and displays activity similar to protein-disulfide isomerases. This protein may play a role in defense against endoplasmic reticulum stress. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

80
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TXNDC12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 70 VUS of 80 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.
1.33LOEUF
pLI 0.000
Z-score 0.80
OE 0.74 (0.43–1.33)
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.
0.52Z-score
OE missense 0.85 (0.71–1.02)
78 obs / 92.0 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.0.74 (0.43–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.71–1.02)
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.0.86
0≤1.21.6
LoF obs/exp: 8 / 10.8Missense obs/exp: 78 / 92.0Syn Z: 0.66

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS70
Likely Benign2
6
Pathogenic
2
Likely Pathogenic
70
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
67
3
0
70
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total06911080

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

View in ClinVar →

Protein Context — Lollipop Plot

TXNDC12 · 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
METTL1-driven epitranscriptomic enhancement of TXNDC12 boosts c-Myc stability through USP5 in HNSCC.
Mai Z et al.·Exp Mol Med
2025
Clinical Value of TXNDC12 Combined With IDH and 1p19q as Biomarkers for Prognosis of Glioma.
Wang X et al.·Pathol Oncol Res
2021
TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin.
Yuan K et al.·Cell Death Differ
2020
Involvement of disulfidptosis in the pathophysiology of autism spectrum disorder.
Liu Y et al.·Life Sci
2025
Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.
Chen W et al.·J Transl Med
2024
Molecular mechanism underlying radiation resistance in esophageal squamous cell carcinoma.
Ran G et al.·Comput Biol Chem
2026Functional
Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients.
Galvan A et al.·Carcinogenesis
2013Cohort
Proteomic Profiling of Non-Muscle Invasive Bladder Cancer Reveals Potential Biomarkers for Recurrence and Progression Risk.
Silva TA et al.·J Proteome Res
2026
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