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Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3 5
  • Tumor Necrosis Factor Ligand Superfamily Member 2 3 4
  • Cachectin 3 4
  • TNF-Alpha 3 4
  • TNFSF2 3 4
  • TNF-A 3 4
  • TNFA 3 4
  • Tumor Necrosis Factor (TNF Superfamily, Member 2) 2
  • Tumor Necrosis Factor Ligand 1F 3
  • Tumor Necrosis Factor-Alpha 3
  • TNF Superfamily, Member 2 2
  • TNF, Macrophage-Derived 3
  • TNF, Monocyte-Derived 3
  • APC1 Protein 3
  • TNLG1F 3
  • DIF 3

External Ids for TNF Gene

Previous HGNC Symbols for TNF Gene

  • TNFA

Previous GeneCards Identifiers for TNF Gene

  • GC06P031606
  • GC06P031597
  • GC06P031314
  • GC06P031647
  • GC06P031652
  • GC06P031543
  • GC06P031330
  • GC06P031614
  • GC06P031622
  • GC06P031629
  • GC06P031640
  • GC06P031655
  • GC06P031668

Summaries for TNF Gene

Entrez Gene Summary for TNF Gene

  • This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

GeneCards Summary for TNF Gene

TNF (Tumor Necrosis Factor) is a Protein Coding gene. Diseases associated with TNF include Migraine With Or Without Aura 1 and Asthma. Among its related pathways are Hematopoietic cell lineage and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. GO annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is LTA.

UniProtKB/Swiss-Prot for TNF Gene

  • Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key Ser-418 residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918).

  • The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

Tocris Summary for TNF Gene

  • NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in the cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immunological response to infections.

Gene Wiki entry for TNF Gene

Additional gene information for TNF Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TNF Gene

Genomics for TNF Gene

Regulatory Elements for TNF Gene

Enhancers for TNF Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06H031567 2 FANTOM5 Ensembl ENCODE dbSUPER 87.6 +2.9 2852 22.2 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A DMAP1 YBX1 ZNF2 ZBTB7B TNF DDX39B LY6G5B ATF6B LSM2 TCF19 MDC1 DHX16 NFKBIL1 C6orf47
GH06H031563 1.6 FANTOM5 Ensembl ENCODE 31.2 -12.1 -12090 1.6 HDAC1 HDGF ATF1 TBL1XR1 ARNT ZBTB40 TCF12 GATA2 EGR1 ZSCAN5C TNF MICB ATP6V1G2 HLA-C HCG23 HLA-B STK19 CLIC1 LST1 LTA
GH06H031562 0.8 FANTOM5 43 -13.3 -13328 0.4 TBL1XR1 BATF ZFHX2 POLR2A EED ATF7 ETV6 RUNX3 IKZF2 CREM TNF ATP6V1G2 STK19 HLA-B LST1 HSPA1B LTA LOC100287329
GH06H031733 1.9 FANTOM5 ENCODE dbSUPER 3.5 +161.9 161888 8.5 MLX ZFP64 YBX1 FEZF1 DMAP1 YY1 SLC30A9 SP3 NFYC ZC3H11A LY6G5B ATF6B DDX39B LSM2 CSNK2B GPANK1 VARS NFKBIL1 SKIV2L MSH5
GH06H031817 1.7 FANTOM5 ENCODE dbSUPER 2.3 +247.2 247213 10.7 ZFP64 DMAP1 YY1 SP3 NFYC ZC3H11A PPARGC1A MEF2D SSRP1 ZNF610 BAG6 ATF6B GPANK1 LSM2 DDX39B VARS CSNK2B SKIV2L LY6G5B RPL3P2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around TNF on UCSC Golden Path with GeneCards custom track

Promoters for TNF Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000195562 433 801 HDGF PKNOX1 TBL1XR1 RB1 SIN3A GATA2 ZNF366 ATF7 RUNX3 IKZF2

Genomic Locations for TNF Gene

Genomic Locations for TNF Gene
chr6:31,575,567-31,578,336
(GRCh38/hg38)
Size:
2,770 bases
Orientation:
Plus strand
chr6:31,543,344-31,546,113
(GRCh37/hg19)

Genomic View for TNF Gene

Genes around TNF on UCSC Golden Path with GeneCards custom track

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

Proteins for TNF Gene

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

    Protein Symbol:
    P01375-TNFA_HUMAN
    Recommended name:
    Tumor necrosis factor
    Protein Accession:
    P01375
    Secondary Accessions:
    • O43647
    • Q9P1Q2
    • Q9UIV3

    Protein attributes for TNF Gene

    Size:
    233 amino acids
    Molecular mass:
    25644 Da
    Quaternary structure:
    • Homotrimer. Interacts with SPPL2B.
    SequenceCaution:
    • Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Evidence={ECO:0000305}; Sequence=CAA75070.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TNF Gene

neXtProt entry for TNF Gene

Post-translational modifications for TNF Gene

  • O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
  • The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
  • The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.
  • Glycosylation at Ser80
  • Modification sites at PhosphoSitePlus

Other Protein References for TNF Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Assay Products

No data available for DME Specific Peptides for TNF Gene

Domains & Families for TNF Gene

Gene Families for TNF Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Disease related genes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry

P01375

UniProtKB/Swiss-Prot:

TNFA_HUMAN :
  • Belongs to the tumor necrosis factor family.
Family:
  • Belongs to the tumor necrosis factor family.
genes like me logo Genes that share domains with TNF: view

Function for TNF Gene

Molecular function for TNF Gene

GENATLAS Biochemistry:
tumor necrosis factor,alpha (cachectin),potent proinflammatory cytokine,involved in inflammatory and immune responses,stimulating the sphingomyelinase (SMPD1),enhancing insulin resistance in peripheral tissues of cancer patients,susceptibility factor for narcolepsy and myasthenia gravis and cardiac sarcoidosis,with a common polymorphism in the promoter region (C->A) associated with reduced circulating levels of TNF,mediating neuronal death in injured brain (by inducing resistance to the protective effect of IGF1)
UniProtKB/Swiss-Prot Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key Ser-418 residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918).
UniProtKB/Swiss-Prot Function:
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

LifeMap Function Summary for TNF Gene

It affects the following cells:
TNF as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for TNF Gene

Gene Ontology (GO) - Molecular Function for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IEA,IPI 12777399
GO:0005125 cytokine activity IDA 10748004
GO:0005164 tumor necrosis factor receptor binding IDA 14512626
GO:0005515 protein binding IPI 2848815
GO:0042802 identical protein binding IDA 14512626
genes like me logo Genes that share ontologies with TNF: view
genes like me logo Genes that share phenotypes with TNF: view

Animal Models for TNF Gene

MGI Knock Outs for TNF:

Animal Model Products

Clone Products

  • Addgene plasmids for TNF

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

Localization for TNF Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNF Gene

Cell membrane; Single-pass type II membrane protein.
Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein.
Tumor necrosis factor, soluble form: Secreted.
C-domain 1: Secreted.
C-domain 2: Secreted.

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 TNF gene
Compartment Confidence
plasma membrane 5
extracellular 5
endosome 4
cytoskeleton 3
mitochondrion 3
peroxisome 3
nucleus 3
cytosol 3
endoplasmic reticulum 2
lysosome 2
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001891 phagocytic cup IEA,ISS --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA,IEA 3932069
GO:0005622 intracellular IEA --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with TNF: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TNF Gene

Pathways & Interactions for TNF Gene

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

Pathways by source for TNF Gene

SIGNOR curated interactions for TNF Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000060 protein import into nucleus, translocation IDA 16280327
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IDA,IEA 1618860
GO:0000165 MAPK cascade IMP 21147091
GO:0000185 activation of MAPKKK activity IDA 15310755
GO:0000187 activation of MAPK activity IDA 10748004
genes like me logo Genes that share ontologies with TNF: view

Drugs & Compounds for TNF Gene

(191) Drugs for TNF Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, FDA Approved Drugs, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adalimumab Approved Pharma antibody, Target 512
Etanercept Approved, Investigational Pharma antibody, Target 408
Infliximab Approved Pharma antibody, Target, inhibitor 399
Thalidomide Approved, Investigational, Withdrawn Pharma inhibitor, Target Immunomodulatory agent,sedative drug,angiogenesis inhibitor, Immunomodulatory agents 1173
Certolizumab pegol Approved Pharma antibody, Target, neutralizer 130

(70) Additional Compounds for TNF Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cis,trans-5'-Hydroxythalidomide

(3) Tocris Compounds for TNF Gene

Compound Action Cas Number
Pyrrolidinedithiocarbamate ammonium Inhibits NF-kappaB, prevents increase in NOS mRNA 5108-96-3
SP 100030 NF-kappaB and AP-1 dual inhibitor 154563-54-9
Tanshinone IIA Inhibits NF-kappaB and AP-1 DNA binding. Displays antioxidant properties 568-72-9

(14) ApexBio Compounds for TNF Gene

Compound Action Cas Number
Bay 11-7821(BAY 11-7082) IKK/NF-κB/TNFα inhibitor 19542-67-7
Bioymifi
Calcitriol TNF-α and IL-1β production inhibitor 32222-06-3
Cepharanthine 481-49-2
Lenalidomide (CC-5013) Antineoplastic agent,inhibits angiogenesis 191732-72-6
Lenalidomide hemihydrate 847871-99-2
Lenalidomide hydrochloride TNF-α secretion inhibitor 1243329-97-6
Magnolol Inhibitor of NO/TNF-α production;antifungal agent 528-43-8
Necrostatin 2 In vitro necroptosis inhibitor 852391-19-6
Necrostatin-1 RIP1 inhibitor 4311-88-0
Pomalidomide (CC-4047) Immunomodulator,antumor/anti-angiogenic 19171-19-8
Roquinimex 84088-42-6
Tempol 2226-96-2
Thalidomide Immunomodulatory agent,sedative drug,angiogenesis inhibitor 50-35-1
genes like me logo Genes that share compounds with TNF: view

Drug Products

Transcripts for TNF Gene

mRNA/cDNA for TNF Gene

(1) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(68) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for TNF Gene

Tumor necrosis factor:
Representative Sequences:

Clone Products

  • Addgene plasmids for TNF

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

No ASD Table

Relevant External Links for TNF Gene

GeneLoc Exon Structure for
TNF
ECgene alternative splicing isoforms for
TNF

Expression for TNF Gene

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