The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009] See more...

Aliases for TOX Gene

Aliases for TOX Gene

  • Thymocyte Selection Associated High Mobility Group Box 2 3 5
  • Thymocyte Selection-Associated High Mobility Group Box Protein TOX 3 4
  • Thymus High Mobility Group Box Protein TOX 3 4
  • KIAA0808 4
  • TOX1 3

External Ids for TOX Gene

Previous GeneCards Identifiers for TOX Gene

  • GC08M059657
  • GC08M059441
  • GC08M059767
  • GC08M059880
  • GC08M059717
  • GC08M055205

Summaries for TOX Gene

Entrez Gene Summary for TOX Gene

  • The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009]

GeneCards Summary for TOX Gene

TOX (Thymocyte Selection Associated High Mobility Group Box) is a Protein Coding gene. Diseases associated with TOX include Cutaneous Diphtheria and Polycystic Echinococcosis. Among its related pathways are Development and heterogeneity of the ILC family and Mesodermal Commitment Pathway. Gene Ontology (GO) annotations related to this gene include chromatin binding. An important paralog of this gene is TOX3.

UniProtKB/Swiss-Prot Summary for TOX Gene

  • Transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis (By similarity). Binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA. During cortical development, controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. Beyond progenitor cells, promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. May activate or repress critical genes for neural stem cell fate such as SOX2, EOMES and ROBO2 (By similarity). Plays an essential role in the development of lymphoid tissue-inducer (LTi) cells, a subset necessary for the formation of secondary lymphoid organs: peripheral lymph nodes and Peyer's patches. Acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment. Required for the development of various T cell subsets, including CD4-positive helper T cells, CD8-positive cytotoxic T cells, regulatory T cells and CD1D-dependent natural killer T (NKT) cells. Required for the differentiation of common lymphoid progenitors (CMP) to innate lymphoid cells (ILC) (By similarity). May regulate the NOTCH-mediated gene program, promoting differentiation of the ILC lineage. Required at the progenitor phase of NK cell development in the bone marrow to specify NK cell lineage commitment (PubMed:21126536) (By similarity). Upon chronic antigen stimulation, diverts T cell development by promoting the generation of exhaustive T cells, while suppressing effector and memory T cell programming. May regulate the expression of genes encoding inhibitory receptors such as PDCD1 and induce the exhaustion program, to prevent the overstimulation of T cells and activation-induced cell death (By similarity).

Gene Wiki entry for TOX Gene

Additional gene information for TOX Gene

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

Genomics for TOX Gene

GeneHancer (GH) Regulatory Elements for TOX Gene

Promoters and enhancers for TOX 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 TOX on UCSC Golden Path with GeneCards custom track

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

Top Transcription factor binding sites by QIAGEN in the TOX gene promoter:
  • GATA-1
  • GATA-2
  • GATA-3
  • NF-AT
  • NF-AT1
  • NF-AT2
  • NF-AT3
  • NF-AT4
  • Pax-4a
  • Pax-5

Genomic Locations for TOX Gene

Genomic Locations for TOX Gene
chr8:58,805,412-59,119,208
(GRCh38/hg38)
Size:
313,797 bases
Orientation:
Minus strand
chr8:59,717,977-60,031,767
(GRCh37/hg19)
Size:
313,791 bases
Orientation:
Minus strand

Genomic View for TOX Gene

Genes around TOX on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for TOX Gene

Proteins for TOX Gene

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

    Protein Symbol:
    O94900-TOX_HUMAN
    Recommended name:
    Thymocyte selection-associated high mobility group box protein TOX
    Protein Accession:
    O94900
    Secondary Accessions:
    • Q96AV5

    Protein attributes for TOX Gene

    Size:
    526 amino acids
    Molecular mass:
    57513 Da
    Quaternary structure:
    • Interacts with HBO1 complex composed at least of KAT7/HBO1, ING4, MEAF6, and JADE2; this complex is involved in histone acetylation. Interacts with DNMT1, LEO1, PAF1, SAP130 and SIN3A; these interactors regulate chromatin remodeling. Interacts with an array of proteins involved in RNA processing and translation and DNA replication.
    SequenceCaution:
    • Sequence=BAA34528.2; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for TOX Gene

Post-translational modifications for TOX Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TOX Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TOX Gene

Domains & Families for TOX Gene

Gene Families for TOX Gene

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

Protein Domains for TOX Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TOX Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ54205, highly similar to Thymus high mobility group box protein TOX (B4DYA1_HUMAN)
  • Thymus high mobility group box protein TOX (TOX_HUMAN)
genes like me logo Genes that share domains with TOX: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TOX Gene

Function for TOX Gene

Molecular function for TOX Gene

UniProtKB/Swiss-Prot Function:
Transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis (By similarity). Binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA. During cortical development, controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. Beyond progenitor cells, promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. May activate or repress critical genes for neural stem cell fate such as SOX2, EOMES and ROBO2 (By similarity). Plays an essential role in the development of lymphoid tissue-inducer (LTi) cells, a subset necessary for the formation of secondary lymphoid organs: peripheral lymph nodes and Peyer's patches. Acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment. Required for the development of various T cell subsets, including CD4-positive helper T cells, CD8-positive cytotoxic T cells, regulatory T cells and CD1D-dependent natural killer T (NKT) cells. Required for the differentiation of common lymphoid progenitors (CMP) to innate lymphoid cells (ILC) (By similarity). May regulate the NOTCH-mediated gene program, promoting differentiation of the ILC lineage. Required at the progenitor phase of NK cell development in the bone marrow to specify NK cell lineage commitment (PubMed:21126536) (By similarity). Upon chronic antigen stimulation, diverts T cell development by promoting the generation of exhaustive T cells, while suppressing effector and memory T cell programming. May regulate the expression of genes encoding inhibitory receptors such as PDCD1 and induce the exhaustion program, to prevent the overstimulation of T cells and activation-induced cell death (By similarity).
UniProtKB/Swiss-Prot Induction:
Up-regulated during differentiation of NK cells from CD34-positive hematopoietic cells in the presence of IL15. Down-regulated in mature NK cells.

Phenotypes From GWAS Catalog for TOX Gene

Gene Ontology (GO) - Molecular Function for TOX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with TOX: view
genes like me logo Genes that share phenotypes with TOX: view

Animal Models for TOX Gene

MGI Knock Outs for TOX:
  • Tox Tox<tm1.1Kay>
  • Tox Tox<tm1b(KOMP)Wtsi>

Animal Model Products

CRISPR Products

miRNA for TOX Gene

miRTarBase miRNAs that target TOX

Clone Products

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

Localization for TOX Gene

Subcellular locations from UniProtKB/Swiss-Prot for TOX Gene

Nucleus.

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 TOX gene
Compartment Confidence
nucleus 4
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli fibrillar center (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TOX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
genes like me logo Genes that share ontologies with TOX: view

Pathways & Interactions for TOX Gene

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

Pathways by source for TOX Gene

Gene Ontology (GO) - Biological Process for TOX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0030098 lymphocyte differentiation IEA --
GO:0032825 positive regulation of natural killer cell differentiation IEA --
GO:0048535 lymph node development IEA --
GO:0048541 Peyer's patch development IEA --
genes like me logo Genes that share ontologies with TOX: view

No data available for SIGNOR curated interactions for TOX Gene

Drugs & Compounds for TOX Gene

No Compound Related Data Available

Transcripts for TOX Gene

mRNA/cDNA for TOX Gene

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

CRISPR Products

Clone Products

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

No ASD Table

Relevant External Links for TOX Gene

GeneLoc Exon Structure for
TOX

Expression for TOX Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x4.1).

Protein differential expression in normal tissues from HIPED for TOX Gene

This gene is overexpressed in CD8 Tcells (57.3) and Testis (11.7).

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



Protein tissue co-expression partners for TOX Gene

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

SOURCE GeneReport for Unigene cluster for TOX Gene:

Hs.491805

mRNA Expression by UniProt/SwissProt for TOX Gene:

O94900-TOX_HUMAN
Tissue specificity: Expressed in NK cells (PubMed:21126536). Highly expressed in tumor-infiltrating CD8-positive T cells (at protein level) (PubMed:31207604).

Evidence on tissue expression from TISSUES for TOX Gene

  • Nervous system(4.5)
  • Blood(2.4)
  • Intestine(2)
genes like me logo Genes that share expression patterns with TOX: view

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

Orthologs for TOX Gene

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

Orthologs for TOX Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TOX 31 30
  • 99.81 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TOX 31
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TOX 31 30
  • 93.85 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TOX 31 30
  • 91.38 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tox 30
  • 89.65 (n)
mouse
(Mus musculus)
Mammalia Tox 17 31 30
  • 89.16 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TOX 31
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves TOX 31 30
  • 85.86 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TOX 31
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tox 30
  • 78.65 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.1457 30
zebrafish
(Danio rerio)
Actinopterygii tox 31 30
  • 67.73 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes POB3 31
  • 6 (a)
OneToMany
Species where no ortholog for TOX was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 TOX Gene

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

Paralogs for TOX Gene

(3) SIMAP similar genes for TOX Gene using alignment to 1 proteins:

  • TOX_HUMAN
genes like me logo Genes that share paralogs with TOX: view

Variants for TOX Gene

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

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
774882 Benign: not provided 58,851,809(-) CAATAAATA/C INTRON_VARIANT
VAR_064759 - p.Ala267Thr

Additional dbSNP identifiers (rs#s) for TOX Gene

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

Variant ID Type Subtype PubMed ID
esv1476730 CNV insertion 17803354
esv1732094 CNV insertion 17803354
esv2737046 CNV deletion 23290073
esv2737047 CNV deletion 23290073
esv3303731 CNV mobile element insertion 20981092
esv3371312 CNV insertion 20981092
esv3417134 CNV insertion 20981092
nsv1124344 CNV deletion 24896259
nsv1125946 CNV tandem duplication 24896259
nsv1133690 CNV deletion 24896259
nsv525018 CNV loss 19592680
nsv526468 CNV loss 19592680
nsv6213 CNV insertion 18451855
nsv6214 CNV insertion 18451855
nsv831327 CNV loss 17160897

Variation tolerance for TOX Gene

Residual Variation Intolerance Score: 76.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.50; 55.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TOX Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for TOX Gene

MalaCards: The human disease database

(8) MalaCards diseases for TOX Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
cutaneous diphtheria
polycystic echinococcosis
  • human polycystic hydatid disease
astigmatism
clostridium difficile colitis
  • pseudomembranous colitis
refractive error
  • refractive errors
- elite association - COSMIC cancer census association via MalaCards
Search TOX in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TOX

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 TOX: view

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

Publications for TOX Gene

  1. Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 9872452) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 2 3 4 54
  2. TOX is a critical regulator of tumour-specific T cell differentiation. (PMID: 31207604) Scott AC … Schietinger A (Nature 2019) 3 4 54
  3. TOX regulates the differentiation of human natural killer cells from hematopoietic stem cells in vitro. (PMID: 21126536) Yun S … Choi I (Immunology letters 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 variants associated with ischemic stroke: the cardiovascular health study. (PMID: 19023099) Luke MM … Psaty BM (Stroke 2009) 3 41 54

Products for TOX Gene

Sources for TOX Gene