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.... See more...

Aliases for TXNIP Gene

Aliases for TXNIP Gene

  • Thioredoxin Interacting Protein 2 3 5
  • VDUP1 2 3 4
  • Upregulated By 1,25-Dihydroxyvitamin D-3 2 3
  • Vitamin D3 Up-Regulated Protein 1 3 4
  • Thioredoxin-Interacting Protein 3 4
  • Thioredoxin Binding Protein 2 2 3
  • EST01027 2 3
  • HHCPA78 2 3
  • ARRDC6 2 3
  • THIF 2 3
  • Thioredoxin-Binding Protein 2 4
  • TXNIP 5

External Ids for TXNIP Gene

Previous GeneCards Identifiers for TXNIP Gene

  • GC01P143959
  • GC01P142025
  • GC01P143165
  • GC01P143187
  • GC01P142927
  • GC01P144149
  • GC01P145438
  • GC01P119402

Summaries for TXNIP Gene

Entrez Gene Summary for TXNIP Gene

  • 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]

GeneCards Summary for TXNIP Gene

TXNIP (Thioredoxin Interacting Protein) is a Protein Coding gene. Diseases associated with TXNIP include Hyperglycemia and Hyperlipidemia, Familial Combined, 3. Among its related pathways are Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways and Innate Immune System. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding and enzyme inhibitor activity. An important paralog of this gene is ARRDC4.

UniProtKB/Swiss-Prot Summary for TXNIP Gene

  • May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).

Gene Wiki entry for TXNIP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TXNIP Gene

Genomics for TXNIP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TXNIP Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TXNIP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TXNIP

Top Transcription factor binding sites by QIAGEN in the TXNIP gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • p53
  • PPAR-gamma1
  • PPAR-gamma2
  • ZIC2

Genomic Locations for TXNIP Gene

Genomic Locations for TXNIP Gene
chr1:145,992,435-145,996,579
(GRCh38/hg38)
Size:
4,145 bases
Orientation:
Minus strand
chr1:145,438,462-145,442,635
(GRCh37/hg19)
Size:
4,174 bases
Orientation:
Plus strand

Genomic View for TXNIP Gene

Genes around TXNIP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TXNIP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TXNIP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TXNIP Gene

Proteins for TXNIP Gene

  • Protein details for TXNIP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H3M7-TXNIP_HUMAN
    Recommended name:
    Thioredoxin-interacting protein
    Protein Accession:
    Q9H3M7
    Secondary Accessions:
    • B4E3D3
    • Q16226
    • Q6PML0
    • Q9BXG9

    Protein attributes for TXNIP Gene

    Size:
    391 amino acids
    Molecular mass:
    43661 Da
    Quaternary structure:
    • Homodimer; disulfide-linked. Interacts with TXN/thioredoxin through its redox-active site. Interacts with transcriptional repressors ZBTB16, ZBTB32 and HDAC1. Interacts (via C-terminus) with ITCH (via WW domains). Interacts with DDIT4.

    Three dimensional structures from OCA and Proteopedia for TXNIP Gene

    Alternative splice isoforms for TXNIP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TXNIP Gene

Post-translational modifications for TXNIP Gene

  • Ubiquitinated; undergoes polyubiquitination catalyzed by ITCH resulting in proteasomal degradation.
  • Ubiquitination at Lys26, Lys212, Lys228, Lys233, and Lys287
  • Modification sites at PhosphoSitePlus

Other Protein References for TXNIP Gene

No data available for DME Specific Peptides for TXNIP Gene

Domains & Families for TXNIP Gene

Gene Families for TXNIP Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for TXNIP Gene

Suggested Antigen Peptide Sequences for TXNIP Gene

GenScript: Design optimal peptide antigens:
  • Thioredoxin interacting protein (B1ALI9_HUMAN)
  • Vitamin D3 up-regulated protein 1 (TXNIP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H3M7

UniProtKB/Swiss-Prot:

TXNIP_HUMAN :
  • Belongs to the arrestin family.
Family:
  • Belongs to the arrestin family.
genes like me logo Genes that share domains with TXNIP: view

Function for TXNIP Gene

Molecular function for TXNIP Gene

UniProtKB/Swiss-Prot Function:
May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).
UniProtKB/Swiss-Prot Induction:
By 1,25-dihydroxyvitamin D-3 and TGFB1. Down-regulated in response to oxidative stress.

Phenotypes From GWAS Catalog for TXNIP Gene

Gene Ontology (GO) - Molecular Function for TXNIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004857 enzyme inhibitor activity IEA --
GO:0005515 protein binding IPI 10814541
GO:0031625 ubiquitin protein ligase binding IPI 20068034
genes like me logo Genes that share ontologies with TXNIP: view
genes like me logo Genes that share phenotypes with TXNIP: view

Animal Models for TXNIP Gene

MGI Knock Outs for TXNIP:

Animal Model Products

CRISPR Products

miRNA for TXNIP Gene

miRTarBase miRNAs that target TXNIP

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TXNIP

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TXNIP Gene

Localization for TXNIP Gene

Subcellular locations from UniProtKB/Swiss-Prot for TXNIP Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TXNIP gene
Compartment Confidence
cytosol 5
mitochondrion 4
nucleus 4
plasma membrane 3
extracellular 2
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TXNIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA,IDA 14632196
GO:0005758 mitochondrial intermembrane space IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with TXNIP: view

Pathways & Interactions for TXNIP Gene

genes like me logo Genes that share pathways with TXNIP: view

Pathways by source for TXNIP Gene

SIGNOR curated interactions for TXNIP Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for TXNIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0006606 protein import into nucleus IEA --
GO:0006979 response to oxidative stress IEA --
GO:0007049 cell cycle IEA --
GO:0009612 response to mechanical stimulus IEA --
genes like me logo Genes that share ontologies with TXNIP: view

Drugs & Compounds for TXNIP Gene

(3) Drugs for TXNIP Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for TXNIP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TXNIP: view

Transcripts for TXNIP Gene

mRNA/cDNA for TXNIP Gene

2 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TXNIP

Alternative Splicing Database (ASD) splice patterns (SP) for TXNIP Gene

No ASD Table

Relevant External Links for TXNIP Gene

GeneLoc Exon Structure for
TXNIP

Expression for TXNIP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TXNIP Gene

Protein differential expression in normal tissues from HIPED for TXNIP Gene

This gene is overexpressed in Breast (63.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TXNIP Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TXNIP

SOURCE GeneReport for Unigene cluster for TXNIP Gene:

Hs.709057

Evidence on tissue expression from TISSUES for TXNIP Gene

  • Nervous system(5)
  • Intestine(4.9)
  • Blood(4.9)
  • Lung(4.8)
  • Eye(4.8)
  • Spleen(4.7)
  • Kidney(4.7)
  • Pancreas(4.5)
  • Heart(4.5)
  • Muscle(4.4)
  • Stomach(4.3)
  • Liver(4)
  • Skin(3.6)
  • Lymph node(3.4)
  • Bone marrow(3.1)
  • Thyroid gland(3.1)
  • Adrenal gland(3)
  • Bone(2.9)
  • Gall bladder(2.4)
genes like me logo Genes that share expression patterns with TXNIP: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TXNIP Gene

Orthologs for TXNIP Gene

This gene was present in the common ancestor of chordates.

Orthologs for TXNIP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TXNIP 30
  • 99.66 (n)
Dog
(Canis familiaris)
Mammalia TXNIP 30
  • 91.22 (n)
Cow
(Bos Taurus)
Mammalia TXNIP 30
  • 91.13 (n)
Rat
(Rattus norvegicus)
Mammalia Txnip 30
  • 89.37 (n)
Mouse
(Mus musculus)
Mammalia Txnip 30 17
  • 89.2 (n)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia txnip 30
  • 73.35 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.27568 30
Zebrafish
(Danio rerio)
Actinopterygii txnipa 30
  • 64.29 (n)
txnip 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4823 30
Species where no ortholog for TXNIP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TXNIP Gene

ENSEMBL:
Gene Tree for TXNIP (if available)
TreeFam:
Gene Tree for TXNIP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TXNIP: view image

Paralogs for TXNIP Gene

Paralogs for TXNIP Gene

(3) SIMAP similar genes for TXNIP Gene using alignment to 4 proteins:

  • TXNIP_HUMAN
  • B1ALI9_HUMAN
  • F6RIS4_HUMAN
  • L8E7V6_HUMAN
genes like me logo Genes that share paralogs with TXNIP: view

Variants for TXNIP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TXNIP Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
726040 Benign: not provided 145,994,148(-) A/G SYNONYMOUS_VARIANT
726271 Benign: not provided 145,994,128(-) C/T MISSENSE_VARIANT
775596 Benign: not provided 145,994,685(-) C/A SYNONYMOUS_VARIANT
777922 Benign: not provided 145,994,078(-) C/T MISSENSE_VARIANT
rs6674773 - p.Arg177Gln

Additional dbSNP identifiers (rs#s) for TXNIP Gene

Structural Variations from Database of Genomic Variants (DGV) for TXNIP Gene

Variant ID Type Subtype PubMed ID
nsv1005055 CNV loss 25217958
nsv509457 CNV insertion 20534489
nsv831359 CNV loss 17160897
nsv950948 CNV duplication 24416366

Variation tolerance for TXNIP Gene

Residual Variation Intolerance Score: 25.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.09; 38.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TXNIP Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TXNIP

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TXNIP Gene

Disorders for TXNIP Gene

MalaCards: The human disease database

(5) MalaCards diseases for TXNIP Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TXNIP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TXNIP

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TXNIP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TXNIP Gene

Publications for TXNIP Gene

  1. Isolation and characterization of a novel cDNA from HL-60 cells treated with 1,25-dihydroxyvitamin D-3. (PMID: 8086474) Chen KS … DeLuca HF (Biochimica et biophysica acta 1994) 2 3 4 23
  2. The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. (PMID: 20068034) Zhang P … Yu L (The Journal of biological chemistry 2010) 3 4 23
  3. hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip. (PMID: 18541147) Shin KH … Park NH (Biochemical and biophysical research communications 2008) 3 4 23
  4. Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2). (PMID: 17603038) Liyanage NP … Lou MF (Experimental eye research 2007) 3 4 23
  5. Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus. (PMID: 17381501) van Greevenbroek MM … de Bruin TW (Diabetic medicine : a journal of the British Diabetic Association 2007) 3 23 41

Products for TXNIP Gene

Sources for TXNIP Gene