The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding di... See more...

Aliases for TOX3 Gene

Aliases for TOX3 Gene

  • TOX High Mobility Group Box Family Member 3 2 3 4 5
  • CAG Trinucleotide Repeat-Containing Gene F9 Protein 3 4
  • Trinucleotide Repeat-Containing Gene 9 Protein 3 4
  • TNRC9 3 4
  • CAGF9 3 4
  • Trinucleotide Repeat Containing 9 2

External Ids for TOX3 Gene

Previous HGNC Symbols for TOX3 Gene

  • TNRC9

Previous GeneCards Identifiers for TOX3 Gene

  • GC16M051030
  • GC16M038359

Summaries for TOX3 Gene

Entrez Gene Summary for TOX3 Gene

  • The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2009]

GeneCards Summary for TOX3 Gene

TOX3 (TOX High Mobility Group Box Family Member 3) is a Protein Coding gene. Diseases associated with TOX3 include Restless Legs Syndrome and Female Breast Cancer. Among its related pathways are Ectoderm Differentiation and Mesodermal Commitment Pathway. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and phosphoprotein binding. An important paralog of this gene is TOX.

UniProtKB/Swiss-Prot Summary for TOX3 Gene

  • Transcriptional coactivator of the p300/CBP-mediated transcription complex. Activates transactivation through cAMP response element (CRE) sites. Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts. Stimulates transcription from the estrogen-responsive or BCL-2 promoters. Required for depolarization-induced transcription activation of the C-FOS promoter in neurons. Associates with chromatin to the estrogen-responsive C3 promoter region.

Additional gene information for TOX3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TOX3 Gene

Genomics for TOX3 Gene

GeneHancer (GH) Regulatory Elements for TOX3 Gene

Promoters and enhancers for TOX3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J052544 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +1.7 1662 5.5 EP300 POLR2G ZIC2 ZBTB10 ZBTB26 KLF7 ZBTB25 TGIF2 ZBTB7A U2AF2 TOX3 lnc-CHD9-4 HSALNG0111457
GH16J052549 Enhancer 0.7 ENCODE 500.7 -1.3 -1312 0.2 CTCF TEAD1 KLF9 RAD21 YY1 HDAC1 MYRF ZBTB48 ZGPAT KLF6 TOX3 lnc-CHD9-4 LOC105371265
GH16J052572 Enhancer 1.2 Ensembl ENCODE dbSUPER 12.1 -25.9 -25874 2.9 TCF12 POLR2G NCOR1 KDM6A TCF7 ZBTB25 TGIF2 SKI TEAD1 ZKSCAN8 CHD9 TOX3 LOC105371265 lnc-CHD9-4 CASC16
GH16J052523 Enhancer 1.1 VISTA Ensembl ENCODE dbSUPER 12.1 +21.5 21501 6.2 EP300 TEAD4 KMT2B CTCF FOXA2 YY1 RBM22 SIN3A RAD21 DMAP1 TOX3 lnc-CHD9-4 HSALNG0111457
GH16J052460 Enhancer 0.8 UCNEbase Ensembl 13.9 +86.7 86701 2.2 EP300 IKZF3 PRDM6 NANOG POLR2A ZBTB44 TOX3 HSALNG0111457 ENSG00000279427
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TOX3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TOX3

Top Transcription factor binding sites by QIAGEN in the TOX3 gene promoter:
  • AREB6
  • FOXC1
  • HOXA3
  • IRF-1
  • MyoD
  • Pax-4a
  • RORalpha1
  • S8
  • Sox9
  • SRY

Genomic Locations for TOX3 Gene

Genomic Locations for TOX3 Gene
chr16:52,436,417-52,547,802
(GRCh38/hg38)
Size:
111,386 bases
Orientation:
Minus strand
chr16:52,471,917-52,581,714
(GRCh37/hg19)
Size:
109,798 bases
Orientation:
Minus strand

Genomic View for TOX3 Gene

Genes around TOX3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TOX3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TOX3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TOX3 Gene

Proteins for TOX3 Gene

  • Protein details for TOX3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15405-TOX3_HUMAN
    Recommended name:
    TOX high mobility group box family member 3
    Protein Accession:
    O15405
    Secondary Accessions:
    • B4DRD0
    • B5MCW4

    Protein attributes for TOX3 Gene

    Size:
    576 amino acids
    Molecular mass:
    63342 Da
    Quaternary structure:
    • Homodimer. Interacts with CREB1; the interaction is not depolarization dependent. Interacts with CREBBP (via C-terminus) (By similarity). Interacts (via HGM box) with CITED1 (via C-terminus); the interaction increases estrogen-response element (ERE)-dependent transcription and protection against cell death. Interacts with CREB1 (phosphorylated form).

    Alternative splice isoforms for TOX3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TOX3 Gene

Post-translational modifications for TOX3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for TOX3 Gene

Domains & Families for TOX3 Gene

Gene Families for TOX3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for TOX3 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TOX3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59741, highly similar to Mus musculus TOX high mobility group box family member 3 (Tox3), mRNA (B4DRD0_HUMAN)
  • Trinucleotide repeat-containing gene 9 protein (TOX3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15405

UniProtKB/Swiss-Prot:

TOX3_HUMAN :
  • the C-terminus is required for calcium responsiveness but not for transactivation activity.
Domain:
  • the C-terminus is required for calcium responsiveness but not for transactivation activity.
  • The N-terminus is absolutely necessary for transactivation activity.
genes like me logo Genes that share domains with TOX3: view

Function for TOX3 Gene

Molecular function for TOX3 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional coactivator of the p300/CBP-mediated transcription complex. Activates transactivation through cAMP response element (CRE) sites. Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts. Stimulates transcription from the estrogen-responsive or BCL-2 promoters. Required for depolarization-induced transcription activation of the C-FOS promoter in neurons. Associates with chromatin to the estrogen-responsive C3 promoter region.
UniProtKB/Swiss-Prot Induction:
Up-regulated by GPR39 in neuronal cells.

Phenotypes From GWAS Catalog for TOX3 Gene

Gene Ontology (GO) - Molecular Function for TOX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0003677 DNA binding IEA --
GO:0003682 chromatin binding IDA 21172805
GO:0005515 protein binding IPI 21172805
GO:0034056 estrogen response element binding IDA 21172805
genes like me logo Genes that share ontologies with TOX3: view
genes like me logo Genes that share phenotypes with TOX3: view

Animal Models for TOX3 Gene

MGI Knock Outs for TOX3:
  • Tox3 Tox3<tm1b(KOMP)Mbp>

Animal Model Products

miRNA for TOX3 Gene

miRTarBase miRNAs that target TOX3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TOX3 Gene

Localization for TOX3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TOX3 Gene

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 TOX3 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Cytosol (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TOX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with TOX3: view

Pathways & Interactions for TOX3 Gene

genes like me logo Genes that share pathways with TOX3: view

Pathways by source for TOX3 Gene

Gene Ontology (GO) - Biological Process for TOX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0006915 apoptotic process IEA --
GO:0042981 regulation of apoptotic process IDA 21172805
GO:0043524 negative regulation of neuron apoptotic process IDA 21172805
GO:0045893 positive regulation of transcription, DNA-templated IDA 21172805
genes like me logo Genes that share ontologies with TOX3: view

No data available for SIGNOR curated interactions for TOX3 Gene

Drugs & Compounds for TOX3 Gene

No Compound Related Data Available

Transcripts for TOX3 Gene

mRNA/cDNA for TOX3 Gene

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

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TOX3 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b
SP1:
SP2: -
SP3:
SP4:

Relevant External Links for TOX3 Gene

GeneLoc Exon Structure for
TOX3

Expression for TOX3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TOX3 Gene

mRNA differential expression in normal tissues according to GTEx for TOX3 Gene

This gene is overexpressed in Minor Salivary Gland (x5.1), Colon - Transverse (x4.9), and Stomach (x4.9).

Protein differential expression in normal tissues from HIPED for TOX3 Gene

This gene is overexpressed in Fetal ovary (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TOX3 Gene



Protein tissue co-expression partners for TOX3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TOX3

SOURCE GeneReport for Unigene cluster for TOX3 Gene:

Hs.460789

mRNA Expression by UniProt/SwissProt for TOX3 Gene:

O15405-TOX3_HUMAN
Tissue specificity: Expressed mainly in epithelial cells. Expressed in the central nervous system (CNS), in the ileum and within the brain in the frontal and occipital lobe.

Evidence on tissue expression from TISSUES for TOX3 Gene

  • Nervous system(4.2)
genes like me logo Genes that share expression patterns with TOX3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TOX3 Gene

Orthologs for TOX3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TOX3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TOX3 31 30
  • 99.85 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TOX3 31
  • 92 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TOX3 31 30
  • 91.44 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TOX3 31 30
  • 91.06 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tox3 17 31 30
  • 90.8 (n)
rat
(Rattus norvegicus)
Mammalia Tox3 30
  • 90.73 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TOX3 31
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves TOX3 31 30
  • 80.58 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TOX3 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tox3 30
  • 75.52 (n)
zebrafish
(Danio rerio)
Actinopterygii tox3 31 30
  • 69.87 (n)
OneToOne
Dr.16177 30
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes POB3 31
  • 7 (a)
OneToMany
Species where no ortholog for TOX3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • 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)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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 TOX3 Gene

ENSEMBL:
Gene Tree for TOX3 (if available)
TreeFam:
Gene Tree for TOX3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TOX3: view image

Paralogs for TOX3 Gene

(4) SIMAP similar genes for TOX3 Gene using alignment to 3 proteins:

  • TOX3_HUMAN
  • H3BTZ9_HUMAN
  • J3QQQ6_HUMAN
genes like me logo Genes that share paralogs with TOX3: view

Variants for TOX3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TOX3 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
717419 Benign: not provided 52,450,405(-) C/T MISSENSE_VARIANT
777016 Benign: not provided 52,439,807(-) G/A SYNONYMOUS_VARIANT
791598 Benign: not provided 52,439,419(-) G/A MISSENSE_VARIANT
rs13332816 - p.Gln572Pro
rs16951186 - p.Val128Met

Additional dbSNP identifiers (rs#s) for TOX3 Gene

Structural Variations from Database of Genomic Variants (DGV) for TOX3 Gene

Variant ID Type Subtype PubMed ID
esv3582201 CNV loss 25503493
esv3638632 CNV gain 21293372
nsv1065333 CNV gain 25217958
nsv1066719 CNV loss 25217958
nsv1118353 CNV deletion 24896259
nsv457488 CNV loss 19166990
nsv472883 CNV novel sequence insertion 20440878
nsv523458 CNV loss 19592680
nsv572616 CNV loss 21841781
nsv833229 CNV loss 17160897
nsv833230 CNV loss 17160897

Variation tolerance for TOX3 Gene

Residual Variation Intolerance Score: 31.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.21; 69.85% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TOX3 Gene

Human Gene Mutation Database (HGMD)
TOX3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TOX3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TOX3 Gene

Disorders for TOX3 Gene

MalaCards: The human disease database

(4) MalaCards diseases for TOX3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
restless legs syndrome
  • ekbom syndrome
female breast cancer
  • female breast carcinoma
estrogen-receptor positive breast cancer
breast cancer
  • breast cancer, familial
- elite association - COSMIC cancer census association via MalaCards
Search TOX3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TOX3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TOX3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TOX3 Gene

Publications for TOX3 Gene

  1. cDNAs with long CAG trinucleotide repeats from human brain. (PMID: 9225980) Margolis RL … Ross CA (Human genetics 1997) 2 3 4 54
  2. Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. (PMID: 21779176) Winkelmann J … Meitinger T (PLoS genetics 2011) 3 41 54
  3. TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex. (PMID: 21172805) Dittmer S … Methner A (Journal of cell science 2011) 3 4 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study. (PMID: 20605201) Travis RC … Million Women Study Collaborators (Lancet (London, England) 2010) 3 41 54

Products for TOX3 Gene

Sources for TOX3 Gene