Free for academic non-profit institutions. Other users need a Commercial license

Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3 4 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
  • GC06P032311
  • GC06P031629
  • GC06P031640
  • GC06P031655
  • GC06P031668
  • GC06P031673
  • GC06P031996
  • GC06P032174
  • GC06P032186

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 Asthma and Malaria. Among its related pathways are IL-1 Family Signaling Pathways and Immune response IFN alpha/beta signaling pathway. Gene Ontology (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, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity).
  • 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

GeneHancer (GH) Regulatory Elements for TNF Gene

Promoters and enhancers for TNF 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
GH06J031567 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 687.5 +2.9 2854 22.2 SP1 ZFX CTCF ZNF148 NKRF ZNF121 POLR2A ZNF687 ZSCAN21 MAFK TNF ATP6V1G2 LST1 GC06P032556 GC06P032575 GC06P032587 GC06P032596 GC06P032607 GC06P032675 GC06P032683
GH06J031563 Enhancer 1.2 FANTOM5 ENCODE 31.2 -12.1 -12088 1.6 MLLT1 CDC5L BACH1 MCM2 TRIM24 PRDM1 ZNF639 EGR1 SMARCA4 MTA1 TNF MICB BAG6 CCHCR1 CSNK2B DHX16 ATP6V1G2 HLA-C HCG23 HLA-B
GH06J031562 Enhancer 0.8 FANTOM5 43 -13.3 -13325 0.4 CREM MLLT1 IKZF1 IKZF2 TRIM22 ZNF341 EED RUNX3 BCL11A NR2F1 LTA TNF ATP6V1G2 STK19 HLA-B LST1 HSPA1B LOC100287329
GH06J031733 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 3.5 +161.9 161890 8.5 ZNF652 SP1 ZFX ELF3 CC2D1A MNT SIX5 NKRF POLR2A MLLT1 MSH5 CLIC1 MSH5-SAPCD1 LY6G5B DDX39B ATF6B LSM2 NFKBIL1 CSNK2B SKIV2L
GH06J031813 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 2.3 +250.2 250179 25.9 HDGF MTA3 ZNF652 SP1 ZFX CC2D1A ELF3 ZKSCAN8 MNT ZNF148 SNHG32 HSPA1B HSPA1A HSPA1L GC06P032546 ATF6B DDX39B CSNK2B GPANK1 LY6G5B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNF on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TNF gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • p53

Genomic Locations for TNF Gene

Genomic Locations for TNF Gene
chr6:31,575,565-31,578,336
(GRCh38/hg38)
Size:
2,772 bases
Orientation:
Plus strand
chr6:31,543,344-31,546,113
(GRCh37/hg19)
Size:
2,770 bases
Orientation:
Plus strand

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

  • 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.
  • 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.
  • O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
  • Glycosylation at isoforms=80
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TNFA_HUMAN (609)

Other Protein References for TNF Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Protein 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

Suggested Antigen Peptide Sequences for TNF Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor (TNF superfamily, member 2) (B0V0H5_HUMAN)
  • Tumor necrosis factor alpha (B5BUQ6_HUMAN)
  • Tumor necrosis factor alpha (C1K3N5_HUMAN)
  • Tumor necrosis factor (Q5RT83_HUMAN)
  • cDNA, FLJ95875, Homo sapiens tumor necrosis factor (TNF superfamily, member 2)(TNF), mRNA (Q5STB3_HUMAN)

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

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, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity).
UniProtKB/Swiss-Prot Function:
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
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)

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:0000977 RNA polymerase II regulatory region sequence-specific DNA binding ISS --
GO:0002020 protease binding IEA,IPI 12777399
GO:0005125 cytokine activity IDA 10748004
GO:0005164 tumor necrosis factor receptor binding IPI 9435233
GO:0005515 protein binding IPI 2848815
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

CRISPR Products

Clone Products

  • Applied Biological Materials (abm): Clones for TNF - Now 50% OFF >
  • * TNF as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * TNF tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All
  • 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
nucleus 4
endosome 4
mitochondrion 3
cytosol 3
cytoskeleton 2
peroxisome 2
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:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 18355445
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

PathCards logo

SuperPathways for TNF Gene

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

Pathways by source for TNF Gene

Gene Ontology (GO) - Biological Process for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 1618860
GO:0000165 MAPK cascade IMP 21147091
GO:0000185 activation of MAPKKK activity IDA 15310755
GO:0000187 activation of MAPK activity IDA 10748004
GO:0001774 microglial cell activation NAS,IEA 26753638
genes like me logo Genes that share ontologies with TNF: view

Drugs & Compounds for TNF Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adalimumab Approved Pharma Target, antibody 561
Etanercept Approved, Investigational Pharma Target, antibody 434
Infliximab Approved Pharma Target, inhibitor, antibody 445
Thalidomide Approved, Investigational, Withdrawn Pharma Target, inhibitor Immunomodulatory agent,sedative drug,angiogenesis inhibitor, TNF-alpha synthesis inhibitor, Immunomodulatory agents 624
Certolizumab pegol Approved Pharma Target, neutralizer, antibody 140

(68) Additional Compounds for TNF Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cis,trans-5'-Hydroxythalidomide
  • 5'-OH-Thalidomide
SP 100030
154563-54-9

(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

Transcripts for TNF Gene

mRNA/cDNA for TNF Gene

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

Unigene Clusters for TNF Gene

Tumor necrosis factor:
Representative Sequences:

CRISPR Products