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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

TNF Gene

protein-coding   GIFtS: 72
GCID: GC06P031543

Tumor Necrosis Factor

(Previous names: tumor necrosis factor (TNF superfamily, member 2))
(Previous symbol: TNFA)
Microbiology & Infectious Diseases Congress
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at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Tumor Necrosis Factor1 2     Tumor Necrosis Factor (TNF Superfamily, Member 2)1
TNFA1 2 3 5     DIF2
Tumor Necrosis Factor Ligand Superfamily Member 22 3     APC1 Protein2
TNF-a2 3     cachectin2
TNF-alpha2 3     TNF, Macrophage-Derived2
TNFSF22 3     TNF, Monocyte-Derived2
Member 21     Tumor Necrosis Factor-Alpha2
TNF Superfamily1     Cachectin3

External Ids:    HGNC: 118921   Entrez Gene: 71242   Ensembl: ENSG000002328107   OMIM: 1911605   UniProtKB: P013753   

Export aliases for TNF gene to outside databases

Previous GC identifers: GC06P031606 GC06P031597 GC06P031314 GC06P031647 GC06P031652 GC06P031330


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 aphthous stomatitis, and magic syndrome, and among its related super-pathways are HIV-1 Nef- Negative effector of Fas and TNF-alpha and Apoptosis and survival FAS signaling cascades. GO annotations related to this gene include transcription regulatory region DNA binding and identical protein binding. An important paralog of this gene is FASLG.

UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
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
Function: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells

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 cellular responses to stimuli such as cytokines and stress and plays a key role in
regulating the immune response to infection. In unstimulated cells NF-kappaB dimers are sequestered
inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IkappaB). IkappaB inactivates
NF-kappaB by masking the nuclear localization signals (NLS). Activation of NF-kappaB occurs via degradation
of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated
IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB
ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene
expression. NF-kappaB turns on expression of IkappaB forming a negative feedback loop.

Gene Wiki entry for TNF (Tumor necrosis factor-alpha) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000006.11  NC_018917.2  NT_007592.15  NT_113891.2  NT_167244.1  NT_167245.1  NT_167246.1  NT_167247.1  
NT_167248.1  NT_167249.1  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the TNF gene promoter:
         c-Fos   p53   AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): TNF promoter sequence
   Search SABiosciences Chromatin IP Primers for TNF

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TNF


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6p21.3   Ensembl cytogenetic band:  6p21.33   HGNC cytogenetic band: 6p21.3

TNF Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TNF gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P031543:  view genomic region     (about GC identifiers)

Start:
31,543,344 bp from pter      End:
31,546,113 bp from pter
Size:
2,770 bases      Orientation:
plus strand

6/7 alternative locations (see all 7):
Chr6+,NT_167245 2,828,891-2,831,653      Chr6+,NT_167247 2,923,056-2,925,818      Chr6+,NT_113891.2 3,052,966-3,055,728     
Chr6+,NT_167249 2,874,151-2,876,913      Chr6+,NT_167246 2,886,234-2,888,996      Chr6+,NT_167248 2,836,988-2,839,752     

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375 (See protein sequence)
Recommended Name: Tumor necrosis factor precursor  
Size: 233 amino acids; 25644 Da
Subunit: Homotrimer. Interacts with SPPL2B
Subcellular location: Cell membrane; Single-pass type II membrane protein
Subcellular location: Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein
Subcellular location: Tumor necrosis factor, soluble form: Secreted
Subcellular location: C-domain 1: Secreted
Subcellular location: C-domain 2: Secreted
Sequence caution: Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Sequence=CAA75070.1; Type=Erroneous
gene model prediction;
6/13 PDB 3D structures from and Proteopedia for TNF (see all 13):
1A8M (3D)        1TNF (3D)        2AZ5 (3D)        2E7A (3D)        2TUN (3D)        2ZJC (3D)    
Secondary accessions: O43647 Q9P1Q2 Q9UIV3

Explore the universe of human proteins at neXtProt for TNF: NX_P01375

Explore proteomics data for TNF at MOPED 

Post-translational modifications:

  • UniProtKB: 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
  • UniProtKB: 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
  • UniProtKB: O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P01375

  • TNF Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    TNF Protein Expression
    REFSEQ proteins: NP_000585.2  
    ENSEMBL proteins: 
     ENSP00000398698  
    Reactome Protein details: P01375
    Human Recombinant Protein Products for TNF: 
    EMD Millipore Purified and/or Recombinant TNF Protein
    R&D Systems Recombinant & Natural Proteins for TNF (TNF-alpha/TNFSF1A)
    Enzo Life Sciences proteins for TNF
    OriGene Purified Proteins for TNF
    OriGene Protein Over-expression Lysate for TNF
    OriGene MassSpec for TNF 
    OriGene Custom Protein Services for TNF
    GenScript Purified and Recombinant Proteins for TNF
    Novus Biologicals TNF Proteins
    Novus Biologicals TNF Lysate
    Sino Biological Recombinant Protein for TNF
    Browse Sino Biological Cell Lysates 
    ProSpec Recombinant Protein for TNF
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001891phagocytic cup ISS--
    GO:0005576extracellular region TAS--
    GO:0005615extracellular space IDA10443688
    GO:0005622intracellular ----
    GO:0005886plasma membrane TAS--

    TNF for ontologies           About GeneDecksing



    TNF Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of TNF
    R&D Systems Antibodies for TNF (TNF-alpha/TNFSF1A)
    OriGene Antibodies for OriGene Antibodies for TNF (NM_000594  NM_000594  )
    OriGene Custom Antibody Services for TNF
    GenScript Superior Antibodies for TNF
    Novus Biologicals TNF Antibodies
    Abcam antibodies for TNF
    Browse Antibodies at Cloud-Clone Corp. 
    ThermoFisher Antibody for TNF
    LSBio Antibodies in human, mouse, rat for TNF 

    Assay Products for TNF: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for TNF
    R&D Systems Flow Cytometry Kits for TNF (TNF-alpha/TNFSF1A)         (see all)
    GenScript Custom Assay Services for TNF
    Enzo Life Sciences assays for TNF
    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    TNFSF: Tumor necrosis factor (ligand) superfamily

    5 InterPro protein domains:
     IPR002959 TNF_alpha
     IPR006052 TNF
     IPR006053 TNF_a/b/c
     IPR008983 Tumour_necrosis_fac-like_dom
     IPR021184 TNF_CS

    Graphical View of Domain Structure for InterPro Entry P01375

    ProtoNet protein and cluster: P01375

    3 Blocks protein domains:
    IPB002959 Tumour necrosis factor alpha (cachectin) signature
    IPB006052 Tumor Necrosis Factor
    IPB006053 Tumour necrosis factor family signature


    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
    Similarity: Belongs to the tumor necrosis factor family


    TNF for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TNFA_HUMAN, P01375
    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
    Function: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells

         Genatlas biochemistry entry for TNF:
    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)

         Summary:
    During embryonic development, TNF as signaling molecule
    affects the following cells: Fetal Hepatocytes in Liver Lobule

    TNF as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells: Mature dendritic-like cells from Blood, Dendritic-like cells from Blood

         Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002020protease binding IPI12777399
    GO:0005125cytokine activity IDA10748004
    GO:0005164tumor necrosis factor receptor binding IDA14512626
    GO:0005515protein binding IPI11878931
    GO:0042802identical protein binding IDA14512626
         
    TNF for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for TNF:
     Increased cell death in breast 

         15/24 MGI mutant phenotypes (inferred from 19 alleles(MGI details for Tnf) (see all 24):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     digestive/alimentary  embryogenesis  endocrine/exocrine gland  growth/size  hematopoietic system 
     homeostasis/metabolism  immune system  integument  limbs/digits/tail  liver/biliary system 

    TNF for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TNF: Ltb/TnfLtb/tm1.1Dvk Lta/TnfLta/tm1Eug Tnftm1Jods Lta/TnfLta/tm1Fda Tnftm1Sek Tnftm1Gkl
                                                         Tnftm3Gkl Ltb/Tnf/LtaLtb/Tnf/tm1Dvk Tnftm2.1Gkl Tnftm1Ljo Tnftm1.2Sned Lta/TnfLta/tm1Jods Tnftm2Gkl

       inGenious Targeting Laboratory - Custom generated mouse model solutions for TNF 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for TNF

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TNF 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TNF 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TNF
    8/29 QIAGEN miScript miRNA Assays for microRNAs that regulate TNF (see all 29):
    hsa-miR-549 hsa-miR-875-3p hsa-miR-181c hsa-miR-3141 hsa-miR-4263 hsa-miR-331-3p hsa-miR-301a hsa-miR-181a-2*
    SwitchGear 3'UTR luciferase reporter plasmidTNF 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for TNF
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TNF

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TNF
    Sirion Biotech Customized adenovirus for overexpression of TNF

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for TNF (see all 7)
    OriGene ORF clones in mouse, rat for TNF
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TNF (NM_001192)
    Sino Biological Human cDNA Clone for TNF
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TNF
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TNF
    Sirion Biotech Customized lentivirus for stable overexpression of TNF 
                         Customized lentivirus expression plasmids for stable overexpression of TNF 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for TNF
    Search LifeMap BioReagents cell lines for TNF
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TNF


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for TNF About   (see all 96)                                                                                              See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1TWEAK Pathway
    TNFR1 Pathway0.56
    Apoptotic Pathways Triggered By HIV10.42
    TNF Signaling0.55
    Apoptosis through Death Receptors0.42
    Apoptosis and survival TNFR1 signaling pathway0.52
    TWEAK Signaling Pathway0.31
    HIV-1 Nef- Negative effector of Fas and TNF-alpha0.46
    2Apoptosis and survival Caspase cascade
    Apoptosis and survival Caspase cascade0.44
    Caspase cascade in apoptosis0.42
    FAS pathway and Stress induction of HSP regulation0.44
    3Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
    Immune response IL-9 signaling pathway0.42
    Adipocytokines & Insulin Signaling0.34
    IL-9 Pathway0.36
    4PEDF Induced Signaling
    MIF Mediated Glucocorticoid Regulation0.94
    IL-6 Pathway0.61
    MIF Regulation of Innate Immune Cells0.94
    STAT3 Pathway0.47
    PEDF Induced Signaling0.73
    Endothelin-1 Signaling Pathway0.46
    all-trans-Retinoic Acid Signaling in Brain0.71
    Cytokine-cytokine receptor interaction0.43
    5Allograft rejection
    Allograft rejection0.69
    Asthma0.47
    Type I diabetes mellitus0.69
    THC Differentiation Pathway0.37
    Graft-versus-host disease0.65
    Antigen processing and presentation0.37

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5/14 EMD Millipore Pathways for TNF (see all 14)
        Immune response CD16 signaling in NK cells
    Immune response IL-9 signaling pathway
    Immune response MIF-mediated glucocorticoid regulation
    Immune response MIF in innate immunity response
    Immune response IL-1 signaling pathway

    5/8 R&D Systems Pathways for TNF (see all 8)
        NOD-like Receptor Signaling Pathways
    TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions
    Adipocytokines & Insulin Signaling
    Th1 Differentiation
    Toll-Like receptor Signaling Pathways

    5/50 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TNF (see all 50)
        Caspase Cascade
    THC Differentiation Pathway
    14-3-3 Induced Apoptosis
    Molecular Mechanisms of Cancer
    Antioxidant Action of Vitamin-C

    1 Cell Signaling Technology (CST) Pathway for TNF
        NF-kappaB Signaling

    5/15 GeneGo (Thomson Reuters) Pathways for TNF (see all 15)
        Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway
    Immune response MIF-mediated glucocorticoid regulation
    Apoptosis and survival Caspase cascade
    Immune response MIF in innate immunity response
    Immune response IL-9 signaling pathway

    5/35 BioSystems Pathways for TNF (see all 35)
        MAPK signaling pathway
    EBV LMP1 signaling
    Apoptosis
    Cytokines and Inflammatory Response
    MicroRNAs in cardiomyocyte hypertrophy

    3 Sino Biological Pathways for TNF 
        TNF Signaling
    Death Receptor Signaling
    NF-kB (NFkB) Pathway

    4        Reactome Pathways for TNF
        Death Receptor Signalling
    TNF signaling
    Extrinsic Pathway for Apoptosis
    Apoptosis


    5/45         Kegg Pathways  (Kegg details for TNF) (see all 45):
        MAPK signaling pathway
    Cytokine-cytokine receptor interaction
    NF-kappa B signaling pathway
    mTOR signaling pathway
    Apoptosis


    TNF for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for TNF

    STRING Interaction Network Preview (showing 5 interactants - click image to see 24)

    5/113 Interacting proteins for TNF (P013751, 2, 3 ENSP000003986984) via UniProtKB, MINT, STRING, and/or I2D (see all 113)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    IKBKGQ9Y6K92, 3MINT-8410390 I2D: score=1 
    RBCK1Q9BYM82, 3MINT-8410390 I2D: score=1 
    RNF31Q96EP02, 3MINT-8410390 I2D: score=1 
    TNFAIP3P215802, 3MINT-8410390 I2D: score=1 
    ENSG00000096150P622693I2D: score=1 
    About this table

    Gene Ontology (GO): 5/122 biological process terms (GO ID links to tree view) (see all 122):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000060protein import into nucleus, translocation IDA16280327
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IDA15345745
    GO:0000165MAPK cascade IMP--
    GO:0000185activation of MAPKKK activity IDA15310755
    GO:0000187activation of MAPK activity IDA10748004

    TNF for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    TNF for compounds           About GeneDecksing

    EMD Millipore small molecules for TNF:
    Small Molecule - inhibitor
    Enzo Life Sciences drugs & compounds for TNF

    Compounds for TNF available from Tocris Bioscience    About this table
    CompoundAction CAS #
    SC 514IKKbeta inhibitor; attenuates NF-kappaB-induced gene expression[354812-17-2]
    Ro 106-9920Inhibitor of NF-kappaB activation[62645-28-7]
    IMD 0354Inhibitor of IKKbeta[978-62-1]
    CelastrolInhibits TNF-alpha-induced NF-kappaB activation[34157-83-0]
    Bay 11-7085Irreversible inhibitor of TNF-alpha-induced IkappaBalpha phosphorylation[196309-76-9]

    4 HMDB Compounds for TNF    About this table
    CompoundSynonyms CAS #PubMed Ids
    Butyric acid1-Butyrate (see all 25)107-92-616142751
    AtorvastatinAtorvastatin acid (see all 4)134523-00-5--
    Glucosamine2-Amino-2-deoxy-D-glucopyranose (see all 10)3416-24-8--
    Simvastatin(+)-Simvastatin (see all 28)79902-63-9--

    10/12 DrugBank Compounds for TNF (see all 12)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Infliximab-- 170277-31-3targetinhibitor15691299 16622728 11752352 15691217 12110154 17642244 15481318 16052578 16456024 15674127 15804598
    Adalimumab-- 331731-18-1targetantibody11752352 15200343 12044041 14532145 15022409 15046527
    EtanerceptCD120b (see all 7)185243-69-0targetantibody10375846 10206649 10405518 10338381 11752352 10357816
    Thalidomidealpha-phthalimidoglutarimide (see all 5)50-35-1targetinhibitor12167383 12105857 12046682 12113124 11752352 12102294
    AmrinoneAmrinona [inn-spanish] (see all 4)60719-84-8targetinhibitor1611705 10444479 10075051 11805217 11969359
    ChloroquineChloraquine (see all 6)54-05-7target--16418198 16761500 17456179 16870179 16670522
    Clenbuterol-- 37148-27-9targetother/unknown10071758 15021963 17139543 16261833 11193379
    Glucosamine-- 3416-24-8target--16431966 16469053 16445576 12244074 15930455
    Pranlukast-- 103177-37-3targetother/unknown17430359 12801315 12801316
    Certolizumab pegol-- 428863-50-7targetneutralizer23620660

    10/141 Novoseek inferred chemical compound relationships for TNF gene (see all 141)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    infliximab 92.6 1681 16095114 (7), 11961039 (7), 12632433 (7), 15538942 (6) (see all 99)
    etanercept 92 1158 11961039 (8), 19188093 (5), 15005015 (5), 20443835 (5) (see all 99)
    adalimumab 89.5 487 11730333 (10), 19188093 (4), 17343250 (3), 17502862 (3) (see all 99)
    endotoxin 87.3 2305 8687293 (8), 1643887 (7), 9185243 (7), 1770269 (7) (see all 99)
    rantes 83.7 975 16466762 (6), 12663241 (6), 9527395 (6), 12388374 (5) (see all 99)
    pge2 79.9 2340 9298541 (9), 8388910 (8), 1836009 (8), 2378446 (7) (see all 99)
    il 10 79.5 347 19771178 (7), 11166831 (5), 15800006 (5), 12719394 (5) (see all 99)
    pentoxifylline 78.4 990 8189599 (9), 1385797 (8), 7589090 (7), 9486396 (6) (see all 99)
    nitric oxide 76.3 4152 7706743 (11), 8046239 (9), 11566624 (9), 1517576 (8) (see all 99)
    abatacept 74.2 77 19916731 (4), 18590608 (4), 17057043 (3), 18670735 (3) (see all 42)

    5 PharmGKB related drug/compound annotations for TNF gene    About this table
    Drug/compound PharmGKB Annotation
    abacavirCA  
    adalimumabCA  
    carbamazepineCA  
    etanerceptCA  
    infliximabCA  

    Search CenterWatch for drugs/clinical trials and news about TNF / TNFA

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for TNF gene: 
    NM_000594.3  

    Unigene Cluster for TNF:

    Tumor necrosis factor
    Hs.241570  [show with all ESTs]
    Unigene Representative Sequence: NM_000594
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000449264(uc003nui.3 uc003nuj.3)
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    hsa-miR-549 hsa-miR-875-3p hsa-miR-181c hsa-miR-3141 hsa-miR-4263 hsa-miR-331-3p hsa-miR-301a hsa-miR-181a-2*
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    Additional mRNA sequence: 

    AB451492.1 AF043342.1 AF098751.1 AJ227911.1 AK314960.1 BC028148.1 FJ795028.1 HQ201306.2 
    M10988.1 X01394.1 

    6 DOTS entries:

    DT.447264  DT.75172441  DT.100717788  DT.121394302  DT.40132506  DT.95165288 

    24/68 AceView cDNA sequences (see all 68):

    CA307225 BM844832 CD364761 CA310368 BM831593 NM_000594 BG232086 X01394 
    BM762686 BM842415 BC028148 CA308256 CA309711 BI910312 AI242177 CD368116 
    CD364988 CA309509 BM922481 CD367845 BI908079 CD367664 BM906148 CA307429 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    TNF expression in normal human tissues (normalized intensities)      TNF embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAGCCCCCTG
    TNF Expression
    About this image


    TNF expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/12 selected tissues (see all 12) fully expand
     
     Blood (Hematopoietic System)    fully expand to see all 3 entries
             Kupffer Cells Sinusoids
             Bone marrow-derived hematopoietic stem cells
             cd31+ cells   
     
     Neural Tube (Nervous System)
             Prosencephalon
     
     Trophoblast (Extraembryonic Tissues)
             8-Cell Embryo Morula
     
     Endothelium (Cardiovascular System)
             cd31+ cells   
     
     Liver (Hepatobiliary System)
             Kupffer Cells Sinusoids

    See TNF Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for TNF

    SOURCE GeneReport for Unigene cluster: Hs.241570
        SABiosciences Expression via Pathway-Focused PCR Arrays including TNF (see all 50): 
              Lung Cancer in human mouse rat
              Antiviral Response in human mouse rat
              Multiple Sclerosis in human mouse rat
              Wound Healing in human mouse rat
              Lymphoma in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of chordates.

    Orthologs for TNF gene from 3/8 species (see all 8)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tnf1 , 5 tumor necrosis factor1, 5 82.9(n)1
    80.17(a)1
      17 (18.59 cM)5
    219261  NM_013693.21  NP_038721.11 
     351993815 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    --
    35(a)
    34(a)
    1 ↔ many
    1 ↔ many
    2(195685950-195692186)
    2(195674701-195679824)
    zebrafish
    (Danio rerio)
    Actinopterygii tnfb6
    tnfa6
    tumor necrosis factor b (TNF superfamily, member 2...
    tumor necrosis factor a (TNF superfamily, member 2...
    24(a)
    24(a)
    many ↔ many
    many ↔ many
    15(33995840-33998916)
    19(27505097-27509684)


    ENSEMBL Gene Tree for TNF (if available)
    TreeFam Gene Tree for TNF (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for TNF gene
    FASLG2  TNFSF152  LTA2  TNFSF142  
    2 SIMAP similar genes for TNF using alignment to 5 protein entries:     TNFA_HUMAN (see all proteins):
    LTA    FASLG

    TNF for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
    Polymorphism: Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]
    Polymorphism: Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162]


    10/131 SNPs in TNF are shown (see all 131)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs18006301,2
    C,F,H--31459428(+) CCCCCC/ACTTAA 1 -- us2k135Minor allele frequency- A:0.14NS MN NA EA WA 4098
    rs46458361,2
    C,F--31459428(+) CCCCCC/ACTTAA 1 -- us2k11Minor allele frequency- A:0.15NS 158
    rs17997241,2
    C,F--31459434(+) CTTAAC/TGAAGA 1 -- us2k130Minor allele frequency- T:0.09NS MN NA EA WA 2962
    rs42481581,2
    C,F,H--31459485(+) AGGACC/TTCCAG 1 -- us2k17Minor allele frequency- T:0.01NS EA NA 808
    rs49870861,2
    C,F,H--31459509(+) GGGACG/ATTTAA 1 -- us2k19Minor allele frequency- A:0.00MN NS EA 804
    rs42481591,2
    C,F,H--31459532(+) ACACAC/ATGGGG 1 -- us2k16Minor allele frequency- A:0.00NS EA 740
    rs27361961,2
    C,H--31459607(-) ATGCTG/TGTTTC 1 -- us2k14Minor allele frequency- T:0.00NS EA 406
    rs27361951,2
    C--31459643(-) AGGCCC/TTCTTC 1 -- us2k10--------
    rs42481601,2
    C,F--31459645(+) AGAAGG/ACCTGC 1 -- us2k13Minor allele frequency- A:0.01NS NA 332
    rs42481611,2
    C,F--31459719(+) CTGCTA/CCCCCC 1 -- us2k14Minor allele frequency- C:0.02NS NA 334

    HapMap Linkage Disequilibrium report for TNF (31543344 - 31546113 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for TNF:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv830627CNV Loss17160897
    nsv462870CNV Loss19166990
    nsv470809CNV Loss18288195
    nsv884418CNV Gain21882294


    Human Gene Mutation Database (HGMD): TNF
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 191160   
    OMIM disorders: 611162  600807  157300  
    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
  • Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with
    psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive,
    erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis
    characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which
    involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that
    can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive
    condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). Note=Disease susceptibility is
    associated with variations affecting the gene represented in this entry

  • 20/736 diseases for TNF (see all 736):    About MalaCards
    aphthous stomatitis    magic syndrome    mycobacterium chelonae    meliodosis
    periodic fever, aphthous stomatitis, pharyngitis and adenitis    new daily-persistent headache    hepatosplenic t-cell lymphoma    visual agnosia
    uveitis    stomatitis    mucocutaneous leishmaniasis    tuberculous uveitis
    adult pulmonary langerhans cell histiocytosis    central nervous system vasculitis    punctate inner choroidopathy    pediatric ulcerative colitis
    central nervous system leukemia    mycobacterium marinum    tuberculoid leprosy    clostridium sordellii

    20/24 diseases from the University of Copenhagen DISEASES database for TNF (see all 24):
    Rheumatoid arthritis     Crohn's disease     Cancer     Hypersensitivity reaction type II disease
    Vascular disease     Malaria     Psoriasis     Psoriatic arthritis
    Connective tissue disease     Tuberculosis     Ankylosing spondylitis     Asthma
    Multiple sclerosis     Peritonitis     Diabetes mellitus     Liver disease
    Pneumonia     Ulcerative colitis     Uveitis     Kidney disease

    TNF for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/96 Novoseek inferred disease relationships for TNF gene (see all 96)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 99 80542 15626980 (12), 1595815 (11), 2374209 (11), 10561634 (10) (see all 99)
    tumors 96.4 68579 15626980 (12), 1595815 (11), 2374209 (11), 10561634 (10) (see all 99)
    inflammation 92.2 3272 17482668 (5), 20439544 (5), 7737534 (4), 9042105 (4) (see all 99)
    rheumatoid arthritis 90.1 2641 1802490 (5), 15879156 (4), 8329189 (4), 19560810 (4) (see all 99)
    arthritis psoriatic 79 279 16284098 (4), 9326391 (4), 15838232 (3), 14678719 (3) (see all 99)
    sepsis 78.9 1166 1860332 (7), 15526005 (6), 2064171 (5), 8403981 (5) (see all 99)
    tumor necrosis factor receptor-associated periodic syndrome 78.8 119 12352631 (2), 15689926 (2), 18347298 (2), 15492850 (2) (see all 82)
    spondylitis ankylosing 77.7 312 9704649 (4), 15838232 (3), 17414952 (3), 16763453 (3) (see all 99)
    shock septic 77.7 621 9366763 (8), 2285204 (5), 8318801 (5), 10966243 (4) (see all 99)
    arthritis 77.5 684 8033415 (5), 9585810 (5), 7589090 (5), 8222316 (4) (see all 99)

    Genetic Association Database (GAD): TNF
    Human Genome Epidemiology (HuGE) Navigator: TNF (2475 documents)
    Tumor Gene Database (TGDB): TNF

    Export disorders for TNF gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for TNF gene, integrated from 9 sources (see all 17042):
    (articles sorted by number of sources associating them with TNF)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. (PubMed id 10369255)1, 2, 4, 9 Knight J.C....Kwiatkowski D. (1999)
    2. Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. (PubMed id 12915457)1, 2, 4 Kim Y.J.... Shin H.D. (2003)
    3. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. (PubMed id 12746914)1, 2, 4 Balding J.... FitzGerald O. (2003)
    4. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. (PubMed id 6392892)1, 2, 3 Pennica D.... Goeddel D.V. (1984)
    5. The tumor necrosis factor polymorphism TNF (-308) is associated with susceptibility to meningococcal sepsis, but not with lethality. (PubMed id 19242354)1, 4, 9 Read R.C....Wilson A.G. (2009)
    6. Association between the level of circulating bioactive tumor necrosis factor alpha and the tumor necrosis factor alpha gene polymorphism at -308 in patients with rheumatoid arthritis treated with a tumor necrosis factor alpha inhibitor. (PubMed id 18438841)1, 4, 9 Marotte H....Miossec P. (2008)
    7. TNF polymorphism and bronchoalveolar lavage cell TNF-alpha levels in chronic beryllium disease and beryllium sensitization. (PubMed id 17208287)1, 4, 9 Sato H....Maier L.A. (2007)
    8. TNF-alpha gene promoter polymorphism at nucleotide -308 and the inflammatory response and oxidative stress induced by cardiac surgery: role of heart failure and medical treatment. (PubMed id 18450464)1, 4, 9 Galinanes M....Hadjinikolaou L. (2008)
    9. TNFalpha genotype affects TNFalpha release, insulin sensitivity and the severity of liver disease in HCV chronic hepatitis. (PubMed id 16143422)1, 4, 9 Valenti L....Fargion S. (2005)
    10. Association of bladder tumors and GA genotype of -308 nucleotide in tumor necrosis factor-alpha promoter with greater tumor necrosis factor-alpha expression. (PubMed id 15533517)1, 4, 9 Jeong P....Kim W.J. (2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 7124 HGNC: 11892 AceView: TNF Ensembl:ENSG00000232810 euGenes: HUgn7124
    ECgene: TNF Kegg: 7124 H-InvDB: TNF

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for TNF Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TNF Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha
    NIEHS-SNPshttp://egp.gs.washington.edu/data/tnf/
    SeattleSNPshttp://pga.gs.washington.edu/data/tnf/
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for TNF gene:
    Search GeneIP for patents involving TNF

    Licensable Technologies for TNF gene:
    Weizmann Institute:Novel anti-inflammatory and immunomodulatory agents based on oleyl alcohols
    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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    About This Section

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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    (GIFtS: 73)
    transforming growth factor, beta 1
    GIFtS Group
    The GeneCards human gene database gene index: 1 3 5 6 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 


    Developed at the Crown Human Genome Center, Department of Molecular Genetics, the Weizmann Institute of Science

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