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Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3
  • TNFA 3 4 6
  • Tumor Necrosis Factor Ligand Superfamily Member 2 3 4
  • Cachectin 3 4
  • TNF-Alpha 3 4
  • TNFSF2 3 4
  • TNF-A 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

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 mycobacterium chelonae and aphthous stomatitis. Among its related pathways are MAPK signaling pathway and Proteoglycans in cancer. 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).

  • 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 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 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

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 Ser80
  • Modification sites at PhosphoSitePlus

Other Protein References for TNF Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

Protein Products

Assay Products

  • Enzo Life Sciences assays for TNF
  • antibodies-online kits for TNF

No data available for DME Specific Peptides for TNF Gene

Domains for TNF Gene

Gene Families for TNF Gene

HGNC:
  • TNFSF :Tumor necrosis factor (ligand) superfamily

Graphical View of Domain Structure for InterPro Entry

P01375

UniProtKB/Swiss-Prot:

TNFA_HUMAN :
  • P01375
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).
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 11878931
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

CRISPR Products

miRNA for TNF Gene

miRTarBase miRNAs that target TNF

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 Targeting 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
extracellular 5
plasma membrane 5
endosome 3
nucleus 3
cytoskeleton 2
cytosol 2
mitochondrion 2
endoplasmic reticulum 1
golgi apparatus 1
lysosome 1
peroxisome 1
vacuole 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 10443688
GO:0005622 intracellular --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with TNF: view

Pathways for TNF Gene

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

PCR Array Products

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

Compounds for TNF Gene

Compound Products

(3) ApexBio Compounds for TNF Gene

Compound Action Cas Number
Lenalidomide (CC-5013) TNF-alfa secretion inhibitor with IC50 of 13 nM. [191732-72-6]
Necrostatin-1 Necrostatin-1 is a specific RIP1 inhibitor and inhibits TNF-alfa-induced necroptosis with EC50 of 490 nM. [4311-88-0]
Pomalidomide (CC-4047) Pomalidomide, previously known as CC-4047 or actimid, is a potent immunomodulatory molecule that exhibits antineoplastic activity for the treatment of hematological malignancies, especially relapsed and refractory multiple myeloma (MM). [19171-19-8]

(5) Tocris Compounds for TNF Gene

Compound Action Cas Number
IKK 16 Selective inhibitor of IKK [1186195-62-9]
IMD 0354 Inhibitor of IKKbeta [978-62-1]
ML 120B dihydrochloride Novel IKK2-selective inhibitor
Ro 106-9920 Inhibitor of NF-kappaB activation [62645-28-7]
TPCA-1 Potent, selective inhibitor of IKKbeta [507475-17-4]

(4) HMDB Compounds for TNF Gene

Compound Synonyms Cas Number PubMed IDs
Atorvastatin
  • Atorvastatin acid
134523-00-5
Butyric acid
  • 1-Butyrate
107-92-6
Glucosamine
  • 2-Amino-2-deoxy-D-glucopyranose
3416-24-8
Simvastatin
  • (+)-Simvastatin
79902-63-9

(12) Drugbank Compounds for TNF Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Adalimumab
331731-18-1 target antibody
Amrinone
  • Amrinona [inn-spanish]
60719-84-8 target inhibitor
Certolizumab pegol
428863-50-7 target neutralizer
Chloroquine
  • Chloraquine
54-05-7 target
Clenbuterol
37148-27-9 target other/unknown

(141) Novoseek inferred chemical compound relationships for TNF Gene

Compound -log(P) Hits PubMed IDs
infliximab 92.6 272
etanercept 92 245
adalimumab 89.5 138
endotoxin 87.3 397
rantes 83.7 273

(9) PharmGKB related drug/compound annotations for TNF Gene

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

Transcripts for TNF Gene

mRNA/cDNA for TNF Gene

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

Unigene Clusters for TNF Gene

Tumor necrosis factor:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

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

Primer Products

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 (4.3).

Integrated Proteomics: protein expression 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 expressions with TNF: view

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
chimpanzee
(Pan troglodytes)
Mammalia TNF 35
  • 99.71 (n)
  • 99.57 (a)
TNF 36
  • 100 (a)
OneToOne
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
oppossum
(Monodelphis domestica)
Mammalia TNF 36
  • 67 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tnf 35
  • 82.76 (n)
  • 79.74 (a)
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

Selected 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
rs673 -- 31,575,318(+) CCCTC(A/G)GAATC upstream-variant-2KB
rs361525 -- 31,575,324(+) GAATC(A/G)GAGCA upstream-variant-2KB
rs1799769 -- 31,576,246(+) TGGGG(-/G)AAGAA intron-variant
rs1800195 -- 31,574,987(+) TCCCT(A/G)CTACC upstream-variant-2KB
rs1800610 -- 31,576,050(-) CTCCA(C/T)GTTTT intron-variant

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

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

MalaCards: The human disease database. (163) Diseases for TNF Gene including...

Search for TNF Gene in MalaCards »

(3) OMIM Diseases for TNF Gene (191160)

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.

(96) Novoseek inferred disease relationships for TNF Gene

Disease -log(P) Hits PubMed IDs
necrosis 99 685
tumors 96.4 704
inflammation 92.2 234
rheumatoid arthritis 90.1 234
arthritis psoriatic 79 134

Relevant External Links for TNF

Genetic Association Database (GAD)
TNF
Human Genome Epidemiology (HuGE) Navigator
TNF
Tumor Gene Database (TGDB):
TNF
genes like me logo Genes that share disorders with TNF: view

Publications for TNF Gene

  1. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. (PMID: 10369255) Knight J.C. … Kwiatkowski D. (Nat. Genet. 1999) 3 4 23 48
  2. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. (PMID: 10450718) Mira J.P. … Dhainaut J.F. (JAMA 1999) 3 23 48
  3. Plasma interleukin-10:Tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications. (PMID: 11023485) May J. … Kremsner P.G. (J. Infect. Dis. 2000) 3 23 48
  4. Lack of association between adult asthma and the tumour necrosis factor alpha-308 polymorphism gene. (PMID: 11106199) Louis R. … Louis E. (Eur. Respir. J. 2000) 3 23 48
  5. Lack of association between promoter polymorphism of the tumor necrosis factor-alpha gene and psoriatic arthritis in Japanese patients. (PMID: 11121160) Hamamoto Y. … Muto M. (J. Invest. Dermatol. 2000) 3 23 48

Products for TNF Gene

  • Addgene plasmids for TNF

Sources for TNF Gene

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