TXNIP

Chr 1

thioredoxin interacting protein

Also known as: ARRDC6, EST01027, HHCPA78, THIF, VDUP1

NCBI Gene: 10628ENSG00000265972UniProt: Q9H3M7

This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

273
ClinVar variants
135
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— TXNIP
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
135 Pathogenic / Likely Pathogenic· 121 VUS of 273 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.55LOEUF
pLI 0.159
Z-score 3.00
OE 0.26 (0.14–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
-1.28Z-score
OE missense 1.25 (1.13–1.38)
262 obs / 209.7 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.0.26 (0.14–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.25 (1.13–1.38)
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.1.61
0≤1.21.6
LoF obs/exp: 5 / 19.1Missense obs/exp: 262 / 209.7Syn Z: -4.22

ClinVar Variant Classifications

273 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic20
VUS121
Likely Benign2
Benign7
Conflicting2
115
Pathogenic
20
Likely Pathogenic
121
VUS
2
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
20
0
20
VUS
0
62
59
0
121
Likely Benign
0
0
2
0
2
Benign
0
2
3
2
7
Conflicting
—2
Total0641992267

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

View in ClinVar →

Protein Context — Lollipop Plot

TXNIP · 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
Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.
Huang XZ et al.·Nat Commun
2023
The thioredoxin antioxidant system.
Lu J et al.·Free Radic Biol Med
2014Review
D-mannose alleviates intervertebral disc degeneration through glutamine metabolism.
Dong ZL et al.·Mil Med Res
2024
TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.
Woo SH et al.·Circ Res
2023
Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma.
Rindler K et al.·Mol Cancer
2021
Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP.
Thielen L et al.·Curr Opin Endocrinol Diabetes Obes
2018Review
β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome.
Amo-Shiinoki K et al.·Sci Transl Med
2025Functional
Target Discovery to Diabetes Therapy-TXNIP From Bench to Bedside With NIDDK.
Shalev A·Endocrinology
2025Review
Anti-miRNA therapeutics for uterine fibroids.
Saxena S et al.·Biomed Pharmacother
2025
Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.
Ma Y et al.·Signal Transduct Target Ther
2025
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