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].

tumor necrosis factorMIM:191160Ensembl:ENSG00000232810HGNC:HGNC:11892PA4356p21.33

GO terms in TNF

Term TypeEvidence TypeGO Term IDGO Des.
MFIPIGO:0002020protease binding
MFIDAGO:0005125cytokine activity
MFIDAGO:0005164tumor necrosis factor receptor binding
MFIPIGO:0005515protein binding
MFIDAGO:0042802identical protein binding
MFIPIGO:0042802identical protein binding
MFIDAGO:0044212transcription regulatory region DNA binding
BPIDAGO:0000060protein import into nucleus, translocation
BPIDAGO:0000122negative regulation of transcription by RNA polymerase II
BPIMPGO:0000165MAPK cascade
BPIDAGO:0000185activation of MAPKKK activity
BPIDAGO:0000187activation of MAPK activity
BPIDAGO:0001819positive regulation of cytokine production
BPIDAGO:0001934positive regulation of protein phosphorylation
BPIEAGO:0001937negative regulation of endothelial cell proliferation
BPIMPGO:0002439chronic inflammatory response to antigenic stimulus
BPIDAGO:0002740negative regulation of cytokine secretion involved in immune response
BPIEAGO:0002876positive regulation of chronic inflammatory response to antigenic stimulus
BPIEAGO:0002925positive regulation of humoral immune response mediated by circulating immunoglobulin
BPIEAGO:0006006glucose metabolic process
BPIDAGO:0006919activation of cysteine-type endopeptidase activity involved in apoptotic process
BPIDAGO:0006954inflammatory response
BPIEAGO:0006959humoral immune response
BPTASGO:0007249I-kappaB kinase/NF-kappaB signaling
BPIEAGO:0007254JNK cascade
BPIDAGO:0008625extrinsic apoptotic signaling pathway via death domain receptors
BPNASGO:0008625extrinsic apoptotic signaling pathway via death domain receptors
BPIEAGO:0008630intrinsic apoptotic signaling pathway in response to DNA damage
BPIDAGO:0009615response to virus
BPTASGO:0009651response to salt stress
BPIEAGO:0010469regulation of signaling receptor activity
BPIDAGO:0010628positive regulation of gene expression
BPIMPGO:0010628positive regulation of gene expression
BPIDAGO:0010629negative regulation of gene expression
BPIEAGO:0010693negative regulation of alkaline phosphatase activity
BPTASGO:0010803regulation of tumor necrosis factor-mediated signaling pathway
BPNASGO:0010888negative regulation of lipid storage
BPTASGO:0019221cytokine-mediated signaling pathway
BPIEAGO:0030198extracellular matrix organization
BPIEAGO:0030316osteoclast differentiation
BPIDAGO:0030730sequestering of triglyceride
BPIDAGO:0030866cortical actin cytoskeleton organization
BPIDAGO:0031334positive regulation of protein complex assembly
BPISSGO:0031622positive regulation of fever generation
BPIDAGO:0031663lipopolysaccharide-mediated signaling pathway
BPIDAGO:0032715negative regulation of interleukin-6 production
BPIDAGO:0032722positive regulation of chemokine production
BPIEAGO:0032729positive regulation of interferon-gamma production
BPIEAGO:0032755positive regulation of interleukin-6 production
BPIMPGO:0032757positive regulation of interleukin-8 production
BPIDAGO:0032800receptor biosynthetic process
BPIDAGO:0033138positive regulation of peptidyl-serine phosphorylation
BPIMPGO:0033209tumor necrosis factor-mediated signaling pathway
BPTASGO:0033209tumor necrosis factor-mediated signaling pathway
BPIDAGO:0034116positive regulation of heterotypic cell-cell adhesion
BPIDAGO:0035509negative regulation of myosin-light-chain-phosphatase activity
BPIDAGO:0043065positive regulation of apoptotic process
BPIMPGO:0043065positive regulation of apoptotic process
BPIDAGO:0043068positive regulation of programmed cell death
BPIDAGO:0043122regulation of I-kappaB kinase/NF-kappaB signaling
BPIDAGO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling
BPIDAGO:0043242negative regulation of protein complex disassembly
BPIDAGO:0043243positive regulation of protein complex disassembly
BPIDAGO:0043280positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
BPIDAGO:0043406positive regulation of MAP kinase activity
BPIMPGO:0043491protein kinase B signaling
BPIDAGO:0043507positive regulation of JUN kinase activity
BPIEAGO:0044130negative regulation of growth of symbiont in host
BPIDAGO:0045071negative regulation of viral genome replication
BPIDAGO:0045080positive regulation of chemokine biosynthetic process
BPIDAGO:0045416positive regulation of interleukin-8 biosynthetic process
BPIDAGO:0045429positive regulation of nitric oxide biosynthetic process
BPNASGO:0045599negative regulation of fat cell differentiation
BPIEAGO:0045662negative regulation of myoblast differentiation
BPIEAGO:0045668negative regulation of osteoblast differentiation
BPIDAGO:0045672positive regulation of osteoclast differentiation
BPIDAGO:0045732positive regulation of protein catabolic process
BPIMPGO:0045785positive regulation of cell adhesion
BPIDAGO:0045860positive regulation of protein kinase activity
BPIDAGO:0045892negative regulation of transcription, DNA-templated
BPIDAGO:0045893positive regulation of transcription, DNA-templated
BPIEAGO:0045930negative regulation of mitotic cell cycle
BPIDAGO:0045944positive regulation of transcription by RNA polymerase II
BPIGIGO:0045944positive regulation of transcription by RNA polymerase II
BPIEAGO:0045994positive regulation of translational initiation by iron
BPIEAGO:0046325negative regulation of glucose import
BPIEPGO:0048566embryonic digestive tract development
BPIDAGO:0048661positive regulation of smooth muscle cell proliferation
BPIDAGO:0050715positive regulation of cytokine secretion
BPIMPGO:0050766positive regulation of phagocytosis
BPIDAGO:0050796regulation of insulin secretion
BPIEAGO:0050830defense response to Gram-positive bacterium
BPIDAGO:0050901leukocyte tethering or rolling
BPIDAGO:0050995negative regulation of lipid catabolic process
BPIEAGO:0051023regulation of immunoglobulin secretion
BPIDAGO:0051044positive regulation of membrane protein ectodomain proteolysis
BPIDAGO:0051091positive regulation of DNA-binding transcription factor activity
BPIDAGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIMPGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIDAGO:0051222positive regulation of protein transport
BPIDAGO:0051384response to glucocorticoid
BPIEAGO:0051798positive regulation of hair follicle development
BPIEAGO:0051897positive regulation of protein kinase B signaling
BPIDAGO:0060557positive regulation of vitamin D biosynthetic process
BPIDAGO:0060559positive regulation of calcidiol 1-monooxygenase activity
BPIEAGO:0060664epithelial cell proliferation involved in salivary gland morphogenesis
BPIEAGO:0060693regulation of branching involved in salivary gland morphogenesis
BPIDAGO:0061048negative regulation of branching involved in lung morphogenesis
BPNASGO:0070374positive regulation of ERK1 and ERK2 cascade
BPIDAGO:0070886positive regulation of calcineurin-NFAT signaling cascade
BPIEAGO:0071230cellular response to amino acid stimulus
BPIDAGO:0071316cellular response to nicotine
BPIDAGO:0071407cellular response to organic cyclic compound
BPTASGO:0071550death-inducing signaling complex assembly
BPNASGO:0071677positive regulation of mononuclear cell migration
BPIDAGO:0071803positive regulation of podosome assembly
BPIEAGO:0072577endothelial cell apoptotic process
BPIDAGO:0072659protein localization to plasma membrane
BPIDAGO:0097191extrinsic apoptotic signaling pathway
BPIDAGO:0097527necroptotic signaling pathway
BPIDAGO:1901224positive regulation of NIK/NF-kappaB signaling
BPIDAGO:1901671positive regulation of superoxide dismutase activity
BPIDAGO:1903140regulation of establishment of endothelial barrier
BPIDAGO:1903347negative regulation of bicellular tight junction assembly
BPIEAGO:1904707positive regulation of vascular smooth muscle cell proliferation
BPIDAGO:1904996positive regulation of leukocyte adhesion to vascular endothelial cell
BPIDAGO:1904999positive regulation of leukocyte adhesion to arterial endothelial cell
BPIDAGO:2000010positive regulation of protein localization to cell surface
BPTASGO:2000304positive regulation of ceramide biosynthetic process
BPIDAGO:2000334positive regulation of blood microparticle formation
BPIDAGO:2000343positive regulation of chemokine (C-X-C motif) ligand 2 production
BPIDAGO:2001240negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
CCISSGO:0001891phagocytic cup
CCTASGO:0005576extracellular region
CCIDAGO:0005615extracellular space
CCTASGO:0005886plasma membrane
CCIDAGO:0005887integral component of plasma membrane
CCISSGO:0009897external side of plasma membrane
CCIDAGO:0009986cell surface
CCIDAGO:0045121membrane raft
CCISSGO:0055037recycling endosome

Gene expression in normal tissue: TNF

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in TNF

DatabasePathway IDPathway Des.
reactomeR-HSA-1266738Developmental Biology
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-168256Immune System
reactomeR-HSA-381340Transcriptional regulation of white adipocyte differentiation
reactomeR-HSA-449147Signaling by Interleukins
reactomeR-HSA-5357786TNFR1-induced proapoptotic signaling
reactomeR-HSA-5357905Regulation of TNFR1 signaling
reactomeR-HSA-5357956TNFR1-induced NFkappaB signaling pathway
reactomeR-HSA-5626978TNFR1-mediated ceramide production
reactomeR-HSA-5668541TNFR2 non-canonical NF-kB pathway
reactomeR-HSA-6783783Interleukin-10 signaling
reactomeR-HSA-6785807Interleukin-4 and Interleukin-13 signaling
reactomeR-HSA-73887Death Receptor Signalling
reactomeR-HSA-75893TNF signaling
biocartacdmacpathwaycadmium induces dna synthesis and proliferation in macrophages
biocartaceramidepathwayceramide signaling pathway
biocartahivnefpathwayhiv-1 nef: negative effector of fas and tnf
biocartahsp27pathwaystress induction of hsp regulation
biocartail10pathwayil-10 anti-inflammatory signaling pathway
biocartail1rpathwaysignal transduction through il1r
biocartakeratinocytepathwaykeratinocyte differentiation
biocartanfatpathwaynfat and hypertrophy of the heart
biocartanfkbpathwaynf-kb signaling pathway
biocartanthipathwaynfkb activation by nontypeable hemophilus influenzae
biocartapparapathwaymechanism of gene regulation by peroxisome proliferators via ppara
biocartasoddpathwaysodd/tnfr1 signaling pathway
biocartastresspathwaytnf/stress related signaling
biocartatnfr1pathwaytnfr1 signaling pathway
biocartavobesitypathwayvisceral fat deposits and the metabolic syndrome
pidamb2_neutrophils_pathwayamb2 Integrin signaling
pidangiopoietinreceptor_pathwayAngiopoietin receptor Tie2-mediated signaling
pidanthraxpathwayCellular roles of Anthrax toxin
pidcaspase_pathwayCaspase Cascade in Apoptosis
pidcd8tcrdownstreampathwayDownstream signaling in naïve CD8+ T cells
pidceramide_pathwayCeramide signaling pathway
pidhdac_classi_pathwaySignaling events mediated by HDAC Class I
pidhivnefpathwayHIV-1 Nef: Negative effector of Fas and TNF-alpha
pidil23pathwayIL23-mediated signaling events
pidil27pathwayIL27-mediated signaling events
pidnfat_tfpathwayCalcineurin-regulated NFAT-dependent transcription in lymphocytes
pidnfkappabcanonicalpathwayCanonical NF-kappaB pathway
pidrxr_vdr_pathwayRXR and RAR heterodimerization with other nuclear receptor
pidtnfpathwayTNF receptor signaling pathway
kegghsa04010MAPK signaling pathway - Homo sapiens (human)
kegghsa04060Cytokine-cytokine receptor interaction - Homo sapiens (human)
kegghsa04064NF-kappa B signaling pathway - Homo sapiens (human)
kegghsa04071Sphingolipid signaling pathway - Homo sapiens (human)
kegghsa04150mTOR signaling pathway - Homo sapiens (human)
kegghsa04210Apoptosis - Homo sapiens (human)
kegghsa04217Necroptosis - Homo sapiens (human)
kegghsa04350TGF-beta signaling pathway - Homo sapiens (human)
kegghsa04380Osteoclast differentiation - Homo sapiens (human)
kegghsa04612Antigen processing and presentation - Homo sapiens (human)
kegghsa04620Toll-like receptor signaling pathway - Homo sapiens (human)
kegghsa04621NOD-like receptor signaling pathway - Homo sapiens (human)
kegghsa04622RIG-I-like receptor signaling pathway - Homo sapiens (human)
kegghsa04625C-type lectin receptor signaling pathway - Homo sapiens (human)
kegghsa04640Hematopoietic cell lineage - Homo sapiens (human)
kegghsa04650Natural killer cell mediated cytotoxicity - Homo sapiens (human)
kegghsa04657IL-17 signaling pathway - Homo sapiens (human)
kegghsa04660T cell receptor signaling pathway - Homo sapiens (human)
kegghsa04664Fc epsilon RI signaling pathway - Homo sapiens (human)
kegghsa04668TNF signaling pathway - Homo sapiens (human)
kegghsa04920Adipocytokine signaling pathway - Homo sapiens (human)
kegghsa04930Type II diabetes mellitus - Homo sapiens (human)
kegghsa04931Insulin resistance - Homo sapiens (human)
kegghsa04932Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
kegghsa04933AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
kegghsa04940Type I diabetes mellitus - Homo sapiens (human)
kegghsa05010Alzheimer,s disease - Homo sapiens (human)
kegghsa05014Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
kegghsa05133Pertussis - Homo sapiens (human)
kegghsa05134Legionellosis - Homo sapiens (human)
kegghsa05140Leishmaniasis - Homo sapiens (human)
kegghsa05142Chagas disease (American trypanosomiasis) - Homo sapiens (human)
kegghsa05143African trypanosomiasis - Homo sapiens (human)
kegghsa05144Malaria - Homo sapiens (human)
kegghsa05145Toxoplasmosis - Homo sapiens (human)
kegghsa05146Amoebiasis - Homo sapiens (human)
kegghsa05152Tuberculosis - Homo sapiens (human)
kegghsa05160Hepatitis C - Homo sapiens (human)
kegghsa05161Hepatitis B - Homo sapiens (human)
kegghsa05164Influenza A - Homo sapiens (human)
kegghsa05165Human papillomavirus infection - Homo sapiens (human)
kegghsa05166HTLV-I infection - Homo sapiens (human)
kegghsa05168Herpes simplex infection - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05310Asthma - Homo sapiens (human)
kegghsa05321Inflammatory bowel disease (IBD) - Homo sapiens (human)
kegghsa05322Systemic lupus erythematosus - Homo sapiens (human)
kegghsa05323Rheumatoid arthritis - Homo sapiens (human)
kegghsa05330Allograft rejection - Homo sapiens (human)
kegghsa05332Graft-versus-host disease - Homo sapiens (human)
kegghsa05410Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
kegghsa05414Dilated cardiomyopathy (DCM) - Homo sapiens (human)
kegghsa05418Fluid shear stress and atherosclerosis - Homo sapiens (human)
wikipathwaysWP129Matrix Metalloproteinases
wikipathwaysWP1449Regulation of toll-like receptor signaling pathway
wikipathwaysWP15Selenium Micronutrient Network
wikipathwaysWP1533Vitamin B12 Metabolism
wikipathwaysWP1544MicroRNAs in cardiomyocyte hypertrophy
wikipathwaysWP1584Type II diabetes mellitus
wikipathwaysWP176Folate Metabolism
wikipathwaysWP2036TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway
wikipathwaysWP2059Alzheimers Disease
wikipathwaysWP231TNF alpha Signaling Pathway
wikipathwaysWP2328Allograft Rejection
wikipathwaysWP2431Spinal Cord Injury
wikipathwaysWP2447Amyotrophic lateral sclerosis (ALS)
wikipathwaysWP2571Polycystic Kidney Disease Pathway
wikipathwaysWP2586Aryl Hydrocarbon Receptor
wikipathwaysWP262EBV LMP1 signaling
wikipathwaysWP2795Cardiac Hypertrophic Response
wikipathwaysWP2864Apoptosis-related network due to altered Notch3 in ovarian cancer
wikipathwaysWP2873Aryl Hydrocarbon Receptor Pathway
wikipathwaysWP2882Nuclear Receptors Meta-Pathway
wikipathwaysWP314Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation
wikipathwaysWP3287Overview of nanoparticle effects
wikipathwaysWP3297EV release from cardiac cells and their functional effects
wikipathwaysWP3599Transcription factor regulation in adipogenesis
wikipathwaysWP3611Photodynamic therapy-induced AP-1 survival signaling.
wikipathwaysWP3617Photodynamic therapy-induced NF-kB survival signaling
wikipathwaysWP3624Lung fibrosis
wikipathwaysWP3639Apoptotic Signaling Pathway
wikipathwaysWP382MAPK Signaling Pathway
wikipathwaysWP3863T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection
wikipathwaysWP3865RIG-I-like Receptor Signaling
wikipathwaysWP3893Development and heterogeneity of the ILC family
wikipathwaysWP3941Oxidative Damage
wikipathwaysWP3980Protein alkylation leading to liver fibrosis
wikipathwaysWP4008NO-cGMP-PKG mediated Neuroprotection
wikipathwaysWP4063Interleukin-10 signaling
wikipathwaysWP4066Interleukin-4 and 13 signaling
wikipathwaysWP4136Fibrin Complement Receptor 3 Signaling Pathway
wikipathwaysWP530Cytokines and Inflammatory Response
wikipathwaysWP560TGF-beta Receptor Signaling
wikipathwaysWP706Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
wikipathwaysWP727Monoamine Transport
wikipathwaysWP75Toll-like Receptor Signaling Pathway
smpdbSMP00358Fc Epsilon Receptor I Signaling in Mast Cells

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in TNF