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Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3
  • 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-Alpha 3
  • TNF, Macrophage-Derived 3
  • TNF, Monocyte-Derived 3
  • TNF Superfamily 2
  • APC1 Protein 3
  • Member 2 2
  • 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

Summaries for TNF Gene

Entrez Gene Summary for TNF Gene

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

GeneCards Summary for TNF Gene

TNF (Tumor Necrosis Factor) is a Protein Coding gene. Diseases associated with TNF include migraine with or without aura 1 and arthritis. Among its related pathways are MAPK signaling pathway and Immune System. GO annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is TNFSF15.

UniProtKB/Swiss-Prot for TNF Gene

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

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

Tocris Summary for TNF Gene

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

Gene Wiki entry for TNF Gene

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

Genomics for TNF Gene

Regulatory Elements for TNF Gene

Genomic Location for TNF Gene

Chromosome:
6
Start:
31,575,567 bp from pter
End:
31,578,336 bp from pter
Size:
2,770 bases
Orientation:
Plus strand

Genomic View for TNF Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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

Proteomics data for TNF Gene at MOPED

Post-translational modifications for TNF Gene

  • O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
  • The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
  • The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.
  • Glycosylation at Ser 80
  • Modification sites at PhosphoSitePlus

Other Protein References for TNF Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Protein Products

No data available for DME Specific Peptides for TNF Gene

Domains & Families for TNF Gene

Gene Families for TNF Gene

Graphical View of Domain Structure for InterPro Entry

P01375

UniProtKB/Swiss-Prot:

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

Function for TNF Gene

Molecular function for TNF Gene

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

LifeMap Function Summary for TNF Gene

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

Gene Ontology (GO) - Molecular Function for TNF Gene

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

Animal Models for TNF Gene

MGI Knock Outs for TNF:

Animal Model Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TNF

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , 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
Jensen Localization Image for TNF Gene COMPARTMENTS Subcellular localization image for TNF gene
Compartment Confidence
cytosol 3
extracellular 3
nucleus 3
plasma membrane 3
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
mitochondrion 2
peroxisome 2
vacuole 2
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TNF Gene

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

Pathways & Interactions for TNF Gene

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

PCR Array Products

SIGNOR curated interactions for TNF Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000060 protein import into nucleus, translocation IDA 16280327
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IDA 15345745
GO:0000165 MAPK cascade IMP 21147091
GO:0000185 activation of MAPKKK activity IDA 15310755
GO:0000187 activation of MAPK activity IDA 10748004
genes like me logo Genes that share ontologies with TNF: view

Drugs & Compounds for TNF Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adalimumab Approved Pharma antibody, Target 411
Infliximab Approved Pharma antibody, Target, inhibitor 327
Certolizumab pegol Approved Pharma antibody, Target, neutralizer 109
Etanercept Approved, Investigational Pharma antibody, Target 0
Thalidomide Approved, Investigational, Withdrawn Pharma inhibitor, Target Immunomodulatory agent,sedative drug,angiogenesis inhibitor, Immunomodulatory agents, TNF-alpha synthesis inhibitor 776

(78) Additional Compounds for TNF Gene - From: NovoSeek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cis,trans-5'-Hydroxythalidomide
Ethyl pyruvate
  • Ethyl 2-oxopropanoate
  • Ethyl 2-oxopropionate
  • Ethyl acetylformate
  • Ethyl alpha-ketopropionate
  • Ethyl pyroracemate
617-35-6
Isopropyl alcohol
  • 2-Propanol
  • 2-Propyl alcohol
  • Alcojel
  • Alkolave
  • Avantin
67-63-0
IKK 16
1186195-62-9
15-deoxy-delta-12,14-prostaglandin j2
87893-55-8
genes like me logo Genes that share compounds with TNF: view

Drug Products

Transcripts for TNF Gene

mRNA/cDNA for TNF Gene

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

Unigene Clusters for TNF Gene

Tumor necrosis factor:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TNF

Flow Cytometry Products

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

No ASD Table

Relevant External Links for TNF Gene

GeneLoc Exon Structure for
TNF
ECgene alternative splicing isoforms for
TNF

Expression for TNF Gene

mRNA expression in normal human tissues for TNF Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TNF Gene

This gene is overexpressed in Whole Blood (x4.3).

Protein differential expression in normal tissues from HIPED for TNF Gene

This gene is overexpressed in CD8 Tcells (41.7) and Bone marrow mesenchymal stem cell (27.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TNF Gene



SOURCE GeneReport for Unigene cluster for TNF Gene Hs.241570

genes like me logo Genes that share expression patterns with TNF: view

Protein tissue co-expression partners for TNF Gene

Primer Products

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for TNF Gene

Orthologs for TNF Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNF Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TNF 35
  • 84.55 (n)
  • 80.26 (a)
TNF 36
  • 80 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TNF 35
  • 91.13 (n)
  • 90.99 (a)
TNF 36
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tnf 35
  • 82.9 (n)
  • 80.17 (a)
Tnf 16
Tnf 36
  • 79 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TNF 35
  • 99.71 (n)
  • 99.57 (a)
TNF 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tnf 35
  • 82.76 (n)
  • 79.74 (a)
oppossum
(Monodelphis domestica)
Mammalia TNF 36
  • 67 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 37 (a)
OneToMany
-- 36
  • 38 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia tnf 35
  • 50.43 (n)
  • 34.36 (a)
zebrafish
(Danio rerio)
Actinopterygii tnfa 36
  • 26 (a)
ManyToMany
tnfb 36
  • 24 (a)
ManyToMany
Species with no ortholog for TNF:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TNF Gene

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

Paralogs for TNF Gene

Paralogs for TNF Gene

(2) SIMAP similar genes for TNF Gene using alignment to 4 proteins:

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

Variants for TNF Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TNF Gene

P01375-TNFA_HUMAN
Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162]

Sequence variations from dbSNP and Humsavar for TNF Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs281865419 Pathogenic, Pathogenic 31,577,157(+) ACCGC(C/T)GGGCC reference, missense
VAR_011927 -
VAR_019378 -

Structural Variations from Database of Genomic Variants (DGV) for TNF Gene

Variant ID Type Subtype PubMed ID
nsv830627 CNV Loss 17160897
nsv470809 CNV Loss 18288195
nsv884418 CNV Gain 21882294
nsv462870 CNV Loss 19166990

Variation tolerance for TNF Gene

Residual Variation Intolerance Score: 47.23% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.55; 11.95% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TNF Gene

HapMap Linkage Disequilibrium report
TNF
Human Gene Mutation Database (HGMD)
TNF

Disorders for TNF Gene

MalaCards: The human disease database

(359) MalaCards diseases for TNF Gene - From: OMIM, ClinVar, DISEASES, NovoSeek, and GeneCards

Disorder Aliases PubMed IDs
migraine with or without aura 1
  • migraine
arthritis
  • inflammatory disorder of joint
toxic shock syndrome
  • tss
pulmonary sarcoidosis
  • lung sarcoidosis
staphylococcal toxic shock syndrome
  • toxic shock syndrome
- elite association
Search TNF in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TNFA_HUMAN
  • 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). {ECO:0000269 PubMed:12746914}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Relevant External Links for TNF

Genetic Association Database (GAD)
TNF
Human Genome Epidemiology (HuGE) Navigator
TNF
Tumor Gene Database (TGDB):
TNF
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TNF
genes like me logo Genes that share disorders with TNF: view

No data available for Genatlas for TNF Gene

Publications for TNF Gene

  1. Activation of toll-like receptor-9 induces matrix metalloproteinase-9 expression through Akt and tumor necrosis factor-alpha signaling. (PMID: 16870179) Lim E.J. … Baek S.H. (FEBS Lett. 2006) 23 25 26 67
  2. Immunopharmacological potential of selective phosphodiesterase inhibition. I. Differential regulation of lipopolysaccharide-mediated proinflammatory cytokine (interleukin-6 and tumor necrosis factor-alpha) biosynthesis in alveolar epithelial cells. (PMID: 11805217) Haddad J.J. … Lauterbach R. (J. Pharmacol. Exp. Ther. 2002) 23 25 26 67
  3. Effect of thalidomide on the skeletal muscle in experimental heart failure. (PMID: 12167383) Vescovo G. … Dalla Libera L. (Eur. J. Heart Fail. 2002) 23 25 26 67
  4. Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids. (PMID: 11969359) Marx D. … Szelenyi I. (Pulm Pharmacol Ther 2002) 23 25 26 67
  5. [Selection of one of the TNF blockers; infliximab and etanercept]. (PMID: 17642244) Mimura T. (Nippon Rinsho 2007) 23 25 67

Products for TNF Gene

  • Addgene plasmids for TNF

Sources for TNF Gene

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