TNF
Summary: 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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| tumor necrosis factor | MIM:191160 | Ensembl:ENSG00000232810 | HGNC:HGNC:11892 | PA435 | 6p21.33 |
GO terms in TNF
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IPI | GO:0002020 | protease binding |
| MF | IDA | GO:0005125 | cytokine activity |
| MF | IDA | GO:0005164 | tumor necrosis factor receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0042802 | identical protein binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IDA | GO:0044212 | transcription regulatory region DNA binding |
| BP | IDA | GO:0000060 | protein import into nucleus, translocation |
| BP | IDA | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| BP | IMP | GO:0000165 | MAPK cascade |
| BP | IDA | GO:0000185 | activation of MAPKKK activity |
| BP | IDA | GO:0000187 | activation of MAPK activity |
| BP | IDA | GO:0001819 | positive regulation of cytokine production |
| BP | IDA | GO:0001934 | positive regulation of protein phosphorylation |
| BP | IEA | GO:0001937 | negative regulation of endothelial cell proliferation |
| BP | IMP | GO:0002439 | chronic inflammatory response to antigenic stimulus |
| BP | IDA | GO:0002740 | negative regulation of cytokine secretion involved in immune response |
| BP | IEA | GO:0002876 | positive regulation of chronic inflammatory response to antigenic stimulus |
| BP | IEA | GO:0002925 | positive regulation of humoral immune response mediated by circulating immunoglobulin |
| BP | IEA | GO:0006006 | glucose metabolic process |
| BP | IDA | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process |
| BP | IDA | GO:0006954 | inflammatory response |
| BP | IEA | GO:0006959 | humoral immune response |
| BP | TAS | GO:0007249 | I-kappaB kinase/NF-kappaB signaling |
| BP | IEA | GO:0007254 | JNK cascade |
| BP | IDA | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors |
| BP | NAS | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors |
| BP | IEA | GO:0008630 | intrinsic apoptotic signaling pathway in response to DNA damage |
| BP | IDA | GO:0009615 | response to virus |
| BP | TAS | GO:0009651 | response to salt stress |
| BP | IEA | GO:0010469 | regulation of signaling receptor activity |
| BP | IDA | GO:0010628 | positive regulation of gene expression |
| BP | IMP | GO:0010628 | positive regulation of gene expression |
| BP | IDA | GO:0010629 | negative regulation of gene expression |
| BP | IEA | GO:0010693 | negative regulation of alkaline phosphatase activity |
| BP | TAS | GO:0010803 | regulation of tumor necrosis factor-mediated signaling pathway |
| BP | NAS | GO:0010888 | negative regulation of lipid storage |
| BP | TAS | GO:0019221 | cytokine-mediated signaling pathway |
| BP | IEA | GO:0030198 | extracellular matrix organization |
| BP | IEA | GO:0030316 | osteoclast differentiation |
| BP | IDA | GO:0030730 | sequestering of triglyceride |
| BP | IDA | GO:0030866 | cortical actin cytoskeleton organization |
| BP | IDA | GO:0031334 | positive regulation of protein complex assembly |
| BP | ISS | GO:0031622 | positive regulation of fever generation |
| BP | IDA | GO:0031663 | lipopolysaccharide-mediated signaling pathway |
| BP | IDA | GO:0032715 | negative regulation of interleukin-6 production |
| BP | IDA | GO:0032722 | positive regulation of chemokine production |
| BP | IEA | GO:0032729 | positive regulation of interferon-gamma production |
| BP | IEA | GO:0032755 | positive regulation of interleukin-6 production |
| BP | IMP | GO:0032757 | positive regulation of interleukin-8 production |
| BP | IDA | GO:0032800 | receptor biosynthetic process |
| BP | IDA | GO:0033138 | positive regulation of peptidyl-serine phosphorylation |
| BP | IMP | GO:0033209 | tumor necrosis factor-mediated signaling pathway |
| BP | TAS | GO:0033209 | tumor necrosis factor-mediated signaling pathway |
| BP | IDA | GO:0034116 | positive regulation of heterotypic cell-cell adhesion |
| BP | IDA | GO:0035509 | negative regulation of myosin-light-chain-phosphatase activity |
| BP | IDA | GO:0043065 | positive regulation of apoptotic process |
| BP | IMP | GO:0043065 | positive regulation of apoptotic process |
| BP | IDA | GO:0043068 | positive regulation of programmed cell death |
| BP | IDA | GO:0043122 | regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IDA | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IDA | GO:0043242 | negative regulation of protein complex disassembly |
| BP | IDA | GO:0043243 | positive regulation of protein complex disassembly |
| BP | IDA | GO:0043280 | positive regulation of cysteine-type endopeptidase activity involved in apoptotic process |
| BP | IDA | GO:0043406 | positive regulation of MAP kinase activity |
| BP | IMP | GO:0043491 | protein kinase B signaling |
| BP | IDA | GO:0043507 | positive regulation of JUN kinase activity |
| BP | IEA | GO:0044130 | negative regulation of growth of symbiont in host |
| BP | IDA | GO:0045071 | negative regulation of viral genome replication |
| BP | IDA | GO:0045080 | positive regulation of chemokine biosynthetic process |
| BP | IDA | GO:0045416 | positive regulation of interleukin-8 biosynthetic process |
| BP | IDA | GO:0045429 | positive regulation of nitric oxide biosynthetic process |
| BP | NAS | GO:0045599 | negative regulation of fat cell differentiation |
| BP | IEA | GO:0045662 | negative regulation of myoblast differentiation |
| BP | IEA | GO:0045668 | negative regulation of osteoblast differentiation |
| BP | IDA | GO:0045672 | positive regulation of osteoclast differentiation |
| BP | IDA | GO:0045732 | positive regulation of protein catabolic process |
| BP | IMP | GO:0045785 | positive regulation of cell adhesion |
| BP | IDA | GO:0045860 | positive regulation of protein kinase activity |
| BP | IDA | GO:0045892 | negative regulation of transcription, DNA-templated |
| BP | IDA | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IEA | GO:0045930 | negative regulation of mitotic cell cycle |
| BP | IDA | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | IGI | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | IEA | GO:0045994 | positive regulation of translational initiation by iron |
| BP | IEA | GO:0046325 | negative regulation of glucose import |
| BP | IEP | GO:0048566 | embryonic digestive tract development |
| BP | IDA | GO:0048661 | positive regulation of smooth muscle cell proliferation |
| BP | IDA | GO:0050715 | positive regulation of cytokine secretion |
| BP | IMP | GO:0050766 | positive regulation of phagocytosis |
| BP | IDA | GO:0050796 | regulation of insulin secretion |
| BP | IEA | GO:0050830 | defense response to Gram-positive bacterium |
| BP | IDA | GO:0050901 | leukocyte tethering or rolling |
| BP | IDA | GO:0050995 | negative regulation of lipid catabolic process |
| BP | IEA | GO:0051023 | regulation of immunoglobulin secretion |
| BP | IDA | GO:0051044 | positive regulation of membrane protein ectodomain proteolysis |
| BP | IDA | GO:0051091 | positive regulation of DNA-binding transcription factor activity |
| BP | IDA | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IMP | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IDA | GO:0051222 | positive regulation of protein transport |
| BP | IDA | GO:0051384 | response to glucocorticoid |
| BP | IEA | GO:0051798 | positive regulation of hair follicle development |
| BP | IEA | GO:0051897 | positive regulation of protein kinase B signaling |
| BP | IDA | GO:0060557 | positive regulation of vitamin D biosynthetic process |
| BP | IDA | GO:0060559 | positive regulation of calcidiol 1-monooxygenase activity |
| BP | IEA | GO:0060664 | epithelial cell proliferation involved in salivary gland morphogenesis |
| BP | IEA | GO:0060693 | regulation of branching involved in salivary gland morphogenesis |
| BP | IDA | GO:0061048 | negative regulation of branching involved in lung morphogenesis |
| BP | NAS | GO:0070374 | positive regulation of ERK1 and ERK2 cascade |
| BP | IDA | GO:0070886 | positive regulation of calcineurin-NFAT signaling cascade |
| BP | IEA | GO:0071230 | cellular response to amino acid stimulus |
| BP | IDA | GO:0071316 | cellular response to nicotine |
| BP | IDA | GO:0071407 | cellular response to organic cyclic compound |
| BP | TAS | GO:0071550 | death-inducing signaling complex assembly |
| BP | NAS | GO:0071677 | positive regulation of mononuclear cell migration |
| BP | IDA | GO:0071803 | positive regulation of podosome assembly |
| BP | IEA | GO:0072577 | endothelial cell apoptotic process |
| BP | IDA | GO:0072659 | protein localization to plasma membrane |
| BP | IDA | GO:0097191 | extrinsic apoptotic signaling pathway |
| BP | IDA | GO:0097527 | necroptotic signaling pathway |
| BP | IDA | GO:1901224 | positive regulation of NIK/NF-kappaB signaling |
| BP | IDA | GO:1901671 | positive regulation of superoxide dismutase activity |
| BP | IDA | GO:1903140 | regulation of establishment of endothelial barrier |
| BP | IDA | GO:1903347 | negative regulation of bicellular tight junction assembly |
| BP | IEA | GO:1904707 | positive regulation of vascular smooth muscle cell proliferation |
| BP | IDA | GO:1904996 | positive regulation of leukocyte adhesion to vascular endothelial cell |
| BP | IDA | GO:1904999 | positive regulation of leukocyte adhesion to arterial endothelial cell |
| BP | IDA | GO:2000010 | positive regulation of protein localization to cell surface |
| BP | TAS | GO:2000304 | positive regulation of ceramide biosynthetic process |
| BP | IDA | GO:2000334 | positive regulation of blood microparticle formation |
| BP | IDA | GO:2000343 | positive regulation of chemokine (C-X-C motif) ligand 2 production |
| BP | IDA | GO:2001240 | negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| CC | ISS | GO:0001891 | phagocytic cup |
| CC | TAS | GO:0005576 | extracellular region |
| CC | IDA | GO:0005615 | extracellular space |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | IDA | GO:0005887 | integral component of plasma membrane |
| CC | ISS | GO:0009897 | external side of plasma membrane |
| CC | IDA | GO:0009986 | cell surface |
| CC | IDA | GO:0045121 | membrane raft |
| CC | ISS | GO:0055037 | recycling endosome |
Gene expression in normal tissue: TNF
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in TNF
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-5357786 | TNFR1-induced proapoptotic signaling |
| reactome | R-HSA-5357905 | Regulation of TNFR1 signaling |
| reactome | R-HSA-5357956 | TNFR1-induced NFkappaB signaling pathway |
| reactome | R-HSA-5626978 | TNFR1-mediated ceramide production |
| reactome | R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway |
| reactome | R-HSA-6783783 | Interleukin-10 signaling |
| reactome | R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| reactome | R-HSA-73887 | Death Receptor Signalling |
| reactome | R-HSA-75893 | TNF signaling |
| biocarta | cdmacpathway | cadmium induces dna synthesis and proliferation in macrophages |
| biocarta | ceramidepathway | ceramide signaling pathway |
| biocarta | hivnefpathway | hiv-1 nef: negative effector of fas and tnf |
| biocarta | hsp27pathway | stress induction of hsp regulation |
| biocarta | il10pathway | il-10 anti-inflammatory signaling pathway |
| biocarta | il1rpathway | signal transduction through il1r |
| biocarta | keratinocytepathway | keratinocyte differentiation |
| biocarta | nfatpathway | nfat and hypertrophy of the heart |
| biocarta | nfkbpathway | nf-kb signaling pathway |
| biocarta | nthipathway | nfkb activation by nontypeable hemophilus influenzae |
| biocarta | pparapathway | mechanism of gene regulation by peroxisome proliferators via ppara |
| biocarta | soddpathway | sodd/tnfr1 signaling pathway |
| biocarta | stresspathway | tnf/stress related signaling |
| biocarta | tnfr1pathway | tnfr1 signaling pathway |
| biocarta | vobesitypathway | visceral fat deposits and the metabolic syndrome |
| netpath | Pathway_TNFalpha | TNFalpha |
| netpath | Pathway_TWEAK | TWEAK |
| pid | amb2_neutrophils_pathway | amb2 Integrin signaling |
| pid | angiopoietinreceptor_pathway | Angiopoietin receptor Tie2-mediated signaling |
| pid | anthraxpathway | Cellular roles of Anthrax toxin |
| pid | caspase_pathway | Caspase Cascade in Apoptosis |
| pid | cd8tcrdownstreampathway | Downstream signaling in naïve CD8+ T cells |
| pid | ceramide_pathway | Ceramide signaling pathway |
| pid | hdac_classi_pathway | Signaling events mediated by HDAC Class I |
| pid | hivnefpathway | HIV-1 Nef: Negative effector of Fas and TNF-alpha |
| pid | il23pathway | IL23-mediated signaling events |
| pid | il27pathway | IL27-mediated signaling events |
| pid | nfat_tfpathway | Calcineurin-regulated NFAT-dependent transcription in lymphocytes |
| pid | nfkappabcanonicalpathway | Canonical NF-kappaB pathway |
| pid | rxr_vdr_pathway | RXR and RAR heterodimerization with other nuclear receptor |
| pid | tnfpathway | TNF receptor signaling pathway |
| kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
| kegg | hsa04060 | Cytokine-cytokine receptor interaction - Homo sapiens (human) |
| kegg | hsa04064 | NF-kappa B signaling pathway - Homo sapiens (human) |
| kegg | hsa04071 | Sphingolipid signaling pathway - Homo sapiens (human) |
| kegg | hsa04150 | mTOR signaling pathway - Homo sapiens (human) |
| kegg | hsa04210 | Apoptosis - Homo sapiens (human) |
| kegg | hsa04217 | Necroptosis - Homo sapiens (human) |
| kegg | hsa04350 | TGF-beta signaling pathway - Homo sapiens (human) |
| kegg | hsa04380 | Osteoclast differentiation - Homo sapiens (human) |
| kegg | hsa04612 | Antigen processing and presentation - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04621 | NOD-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04622 | RIG-I-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04625 | C-type lectin receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04640 | Hematopoietic cell lineage - Homo sapiens (human) |
| kegg | hsa04650 | Natural killer cell mediated cytotoxicity - Homo sapiens (human) |
| kegg | hsa04657 | IL-17 signaling pathway - Homo sapiens (human) |
| kegg | hsa04660 | T cell receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04664 | Fc epsilon RI signaling pathway - Homo sapiens (human) |
| kegg | hsa04668 | TNF signaling pathway - Homo sapiens (human) |
| kegg | hsa04920 | Adipocytokine signaling pathway - Homo sapiens (human) |
| kegg | hsa04930 | Type II diabetes mellitus - Homo sapiens (human) |
| kegg | hsa04931 | Insulin resistance - Homo sapiens (human) |
| kegg | hsa04932 | Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human) |
| kegg | hsa04933 | AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human) |
| kegg | hsa04940 | Type I diabetes mellitus - Homo sapiens (human) |
| kegg | hsa05010 | Alzheimer,s disease - Homo sapiens (human) |
| kegg | hsa05014 | Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human) |
| kegg | hsa05133 | Pertussis - Homo sapiens (human) |
| kegg | hsa05134 | Legionellosis - Homo sapiens (human) |
| kegg | hsa05140 | Leishmaniasis - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05143 | African trypanosomiasis - Homo sapiens (human) |
| kegg | hsa05144 | Malaria - Homo sapiens (human) |
| kegg | hsa05145 | Toxoplasmosis - Homo sapiens (human) |
| kegg | hsa05146 | Amoebiasis - Homo sapiens (human) |
| kegg | hsa05152 | Tuberculosis - Homo sapiens (human) |
| kegg | hsa05160 | Hepatitis C - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05164 | Influenza A - Homo sapiens (human) |
| kegg | hsa05165 | Human papillomavirus infection - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| kegg | hsa05168 | Herpes simplex infection - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05310 | Asthma - Homo sapiens (human) |
| kegg | hsa05321 | Inflammatory bowel disease (IBD) - Homo sapiens (human) |
| kegg | hsa05322 | Systemic lupus erythematosus - Homo sapiens (human) |
| kegg | hsa05323 | Rheumatoid arthritis - Homo sapiens (human) |
| kegg | hsa05330 | Allograft rejection - Homo sapiens (human) |
| kegg | hsa05332 | Graft-versus-host disease - Homo sapiens (human) |
| kegg | hsa05410 | Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human) |
| kegg | hsa05414 | Dilated cardiomyopathy (DCM) - Homo sapiens (human) |
| kegg | hsa05418 | Fluid shear stress and atherosclerosis - Homo sapiens (human) |
| wikipathways | WP129 | Matrix Metalloproteinases |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP15 | Selenium Micronutrient Network |
| wikipathways | WP1533 | Vitamin B12 Metabolism |
| wikipathways | WP1544 | MicroRNAs in cardiomyocyte hypertrophy |
| wikipathways | WP1584 | Type II diabetes mellitus |
| wikipathways | WP176 | Folate Metabolism |
| wikipathways | WP2036 | TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway |
| wikipathways | WP2059 | Alzheimers Disease |
| wikipathways | WP231 | TNF alpha Signaling Pathway |
| wikipathways | WP2328 | Allograft Rejection |
| wikipathways | WP236 | Adipogenesis |
| wikipathways | WP2431 | Spinal Cord Injury |
| wikipathways | WP2447 | Amyotrophic lateral sclerosis (ALS) |
| wikipathways | WP254 | Apoptosis |
| wikipathways | WP2571 | Polycystic Kidney Disease Pathway |
| wikipathways | WP2586 | Aryl Hydrocarbon Receptor |
| wikipathways | WP262 | EBV LMP1 signaling |
| wikipathways | WP2795 | Cardiac Hypertrophic Response |
| wikipathways | WP2864 | Apoptosis-related network due to altered Notch3 in ovarian cancer |
| wikipathways | WP2873 | Aryl Hydrocarbon Receptor Pathway |
| wikipathways | WP2882 | Nuclear Receptors Meta-Pathway |
| wikipathways | WP314 | Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation |
| wikipathways | WP3287 | Overview of nanoparticle effects |
| wikipathways | WP3297 | EV release from cardiac cells and their functional effects |
| wikipathways | WP3599 | Transcription factor regulation in adipogenesis |
| wikipathways | WP3611 | Photodynamic therapy-induced AP-1 survival signaling. |
| wikipathways | WP3617 | Photodynamic therapy-induced NF-kB survival signaling |
| wikipathways | WP3624 | Lung fibrosis |
| wikipathways | WP3639 | Apoptotic Signaling Pathway |
| wikipathways | WP382 | MAPK Signaling Pathway |
| wikipathways | WP3863 | T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection |
| wikipathways | WP3865 | RIG-I-like Receptor Signaling |
| wikipathways | WP3893 | Development and heterogeneity of the ILC family |
| wikipathways | WP3941 | Oxidative Damage |
| wikipathways | WP3980 | Protein alkylation leading to liver fibrosis |
| wikipathways | WP4008 | NO-cGMP-PKG mediated Neuroprotection |
| wikipathways | WP4063 | Interleukin-10 signaling |
| wikipathways | WP4066 | Interleukin-4 and 13 signaling |
| wikipathways | WP4136 | Fibrin Complement Receptor 3 Signaling Pathway |
| wikipathways | WP530 | Cytokines and Inflammatory Response |
| wikipathways | WP560 | TGF-beta Receptor Signaling |
| wikipathways | WP706 | Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways |
| wikipathways | WP727 | Monoamine Transport |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
| smpdb | SMP00358 | Fc Epsilon Receptor I Signaling in Mast Cells |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD494 | Neopeltolide | 1 |
| iGMDRD192 | CIL56 | 3 |
| iGMDRD221 | Tamoxifen | 4 |
| iGMDRD425 | ERASTIN | 3 |
| iGMDRD634 | SCHEMBL2608041 | 2 |
| iGMDRD598 | QS-11 | 3 |
| iGMDRD499 | PDMP | 1 |
| iGMDRD871 | BRD6368 | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in TNF
CLASSFICATION
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