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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)

Explore 783 diseases affiliated with
TNF via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Tumor Necrosis Factor¹ ²		Tumor Necrosis Factor (TNF Superfamily, Member 2)¹
TNFA¹ ² ³ ⁵		APC1 Protein²
TNF-Alpha¹		Cachectin³
TNFSF2¹ ² ³		TNF, Macrophage-Derived²
DIF¹ ²		TNF, Monocyte-Derived²
Tumor Necrosis Factor Ligand Superfamily Member 2² ³		Tumor Necrosis Factor-Alpha²
TNF-A¹		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:

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)

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:

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)

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000006.11 NC_018917.1 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+,ALT_REF_LOCI_1 31,555,632-31,565,733	Chr6+,ALT_REF_LOCI_4 31,505,893-31,508,655	Chr6+,ALT_REF_LOCI_3 31,525,488-31,539,294
Chr6+,ALT_REF_LOCI_2 31,530,756-31,572,712	Chr6+,ALT_REF_LOCI_5 31,534,479-31,537,241	Chr6+,ALT_REF_LOCI_6 31,533,585-31,571,936

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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;

6/12 PDB 3D structures from and Proteopedia for TNF (see all 12):

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

Post-translational modifications:

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

space¹

The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane

form occurs by binding to soluble TNFRSF1A/TNFR1¹

O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P01375

TNF Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000585.2

ENSEMBL proteins:

ENSP00000398698

Reactome Protein details: P01375
Human Recombinant Protein Products:

	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 (see all 3): TNF OriGene Protein Over-expression Lysate: 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
	ProSpec Recombinant Protein for TNF
	Browse Proteins at Uscn

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001891	phagocytic cup	ISS	--
GO:0005615	extracellular space	IDA	18355445
GO:0005622	intracellular	--	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral to plasma membrane	IDA	18355445

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)
	Cell Signaling Technology (CST) Antibodies for TNF (TNF-a)
	OriGene Antibodies (see all 5): TNF OriGene Custom Antibody Services for TNF
	GenScript Superior Antibodies for TNF
	Novus Biologicals TNF Antibodies
	Abcam antibodies for TNF
	Browse Antibodies at Uscn
	ThermoFisher Antibody for TNF

Assay Products for TNF:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems Flow Cytometry Kits for TNF (TNF-alpha/TNFSF1A) (see all)
	GenScript Custom Assay Services for TNF
	Cell Signaling Technology (CST) Sandwich ELISA Kits for TNF (TNF-a)
	Enzo Life Sciences assays for TNF
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TNF for domains About GeneDecksing

5 InterPro domains/families:

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 families:

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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

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: Dendritic-like cells, Mature dendritic-like cells

miRNA Products:		OriGene 3'-UTR Clone: TNF Browse MicroRNA Expression Plasmids
		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 plasmid: TNF 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TNF (see all 7) OriGene shRNA RFP: TNF OriGene siRNA: TNF
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TNF

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TNF

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TNF (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, 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

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

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

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	--
GO:0042802	identical protein binding	IDA	14512626

TNF for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for TNF:

Increased cell death in breast

Animal Models:
     Mouse knock-outs for TNF: Ltb/Tnf^Ltb/tm1.1Dvk Lta/Tnf^Lta/tm1Eug Tnf^tm1Jods Lta/Tnf^Lta/tm1Fda Tnf^tm1Sek Tnf^tm1Gkl
                                               Tnf^tm3Gkl Ltb/Tnf/Lta^{Ltb/Tnf/tm1Dvk} Tnf^tm2.1Gkl Tnf^tm1Ljo Tnf^tm1.2Sned Lta/Tnf^Lta/tm1Jods Tnf^tm2Gkl
     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

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/90 super-pathways (see all 90) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

PEDF Induced Signaling

8/9 pathways (see all 9)
PEDF Induced Signaling	1.00	RAR-Gamma-RXR-Alpha Degradation	0.54
MIF Mediated Glucocorticoid Regulation	0.73	STAT3 Pathway	0.47
MIF Regulation of Innate Immune Cells	0.71	Endothelin-1 Signaling Pathway	0.44
IL-6 Pathway	0.61	Cytokine-cytokine receptor interaction	0.26

TWEAK Pathway

TNFR1 Pathway	0.53	TNF Signaling	0.40
HIV-1 Nef- Negative effector of Fas and TNF-alpha	0.42	Apoptotic Pathways Triggered By HIV1	0.37
Apoptosis and survival_TNFR1 signaling pathway	0.40	Apoptosis through Death Receptors	0.32
Apoptosis and survival TNFR1 signaling pathway	0.40	TWEAK Signaling Pathway	0.31

Allograft rejection

Allograft rejection	1.00	Asthma	0.44
Type I diabetes mellitus	0.67	THC Differentiation Pathway	0.39
Graft-versus-host disease	0.63	Antigen processing and presentation	0.25

Rho Family GTPases

Rho Family GTPases	1.00	MAPK Signaling	0.51
ERK Signaling	0.61	ILK Signaling	0.45
Molecular Mechanisms of Cancer	0.51

Apoptosis and survival_Caspase cascade

	Apoptosis and survival_Caspase cascade	1.00			Caspase cascade in apoptosis	0.42
	Apoptosis and survival Caspase cascade	1.00			FAS pathway and Stress induction of HSP regulation	0.33

Pathway sources
See GeneCards unified pathways
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

5/7 R&D Systems Pathways for TNF (see all 7)

	TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions
	Adipocytokines & Insulin Signaling
	Th1 Differentiation
	Toll-Like receptor Signaling Pathways
	Apoptosis 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

2 Cell Signaling Technology (CST) Pathways for TNF

	Apoptosis and Autophagy
	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

5/34 BioSystems Pathways for TNF (see all 34)

	MicroRNAs in cardiomyocyte hypertrophy
	Notch Signaling Pathway
	Matrix Metalloproteinases
	Adipogenesis
	EBV LMP1 signaling

4 Reactome Pathways for TNF

	Death Receptor Signalling
	TNF signaling
	Extrinsic Pathway for Apoptosis
	Apoptosis

5/35 Kegg Pathways (Kegg details for TNF) (see all 35):

	MAPK signaling pathway
	Cytokine-cytokine receptor interaction
	Apoptosis
	TGF-beta signaling pathway
	Osteoclast differentiation

TNF for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TNF

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

5/108 Interacting proteins for TNF (P01375^{1, 2, 3} ENSP00000398698⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 108)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
IKBKG	Q9Y6K9²^,³	MINT-8410390 I2D: score=1
RBCK1	Q9BYM8²^,³	MINT-8410390 I2D: score=1
RNF31	Q96EP0²^,³	MINT-8410390 I2D: score=1
TNFAIP3	P21580²^,³	MINT-8410390 I2D: score=1
TNFRSF1A	P19438¹^,²^,³, ENSP00000162749⁴	EBI-359977,EBI-299451 MINT-48045 MINT-49295 I2D: score=12 STRING: ENSP00000162749

About this table

Gene Ontology (GO): 5/119 biological process terms (GO ID links to tree view) (see all 119): About this table

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	--
GO:0000185	activation of MAPKKK activity	IDA	15310755
GO:0000187	activation of MAPK activity	IDA	10748004

TNF for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, 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

Compound	Action	CAS #
Piceatannol	Inhibits TNF-induced NF-kappaB activation	[10083-24-6]
Bay 11-7821	Irreversible inhibitor of TNF-alpha-induced IkappaBalpha phosphorylation	[19542-67-7]
Thalidomide	TNF-alpha synthesis inhibitor	[50-35-1]
Bay 11-7085	Irreversible inhibitor of TNF-alpha-induced IkappaBalpha phosphorylation	[196309-76-9]

4 HMDB Compounds for TNF About this table

Compound	Synonyms	CAS #	PubMed Ids
Butyric acid	1-Butyrate (see all 25)	107-92-6	16142751
Atorvastatin	Atorvastatin acid (see all 4)	134523-00-5	--
Glucosamine	2-Amino-2-deoxy-D-glucopyranose (see all 10)	3416-24-8	--
Simvastatin	(+)-Simvastatin (see all 28)	79902-63-9	--

9 DrugBank Compounds for TNF About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Infliximab	--	170277-31-3	target	inhibitor	15691299 16622728 11752352 15691217 12110154 17642244 15481318 16052578 16456024 15674127 15804598
Adalimumab	--	331731-18-1	target	antibody	11752352 15200343 12044041 14532145 15022409 15046527
Etanercept	CD120b (see all 7)	185243-69-0	target	antibody	10375846 10206649 10405518 10338381 11752352 10357816
Thalidomide	alpha-phthalimidoglutarimide (see all 5)	50-35-1	target	inhibitor	12167383 12105857 12046682 12113124 11752352 12102294
Amrinone	Amrinona [inn-spanish] (see all 4)	60719-84-8	target	inhibitor	1611705 10444479 10075051 11805217 11969359
Chloroquine	Chloraquine (see all 6)	54-05-7	target	--	16418198 16761500 17456179 16870179 16670522
Clenbuterol	--	37148-27-9	target	other/unknown	10071758 15021963 17139543 16261833 11193379
Glucosamine	--	3416-24-8	target	--	16431966 16469053 16445576 12244074 15930455
Pranlukast	--	103177-37-3	target	other/unknown	17430359 12801315 12801316

10/141 Novoseek 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

Drug/compound	PharmGKB Annotation
abacavir	CA
adalimumab	CA
carbamazepine	CA
etanercept	CA
infliximab	CA

About this table

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

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
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, 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)

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		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*

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TNF

Additional cDNA 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):

X01394 BM762686 BC028148 BM844832 CD364761 BM842415 CA307225 BG232086

CA310368 NM_000594 BM831593 CD368116 M10988 CA309664 CD368142 BI907528

AA381586 CD366187 BM844831 AJ227911 AI242177 BI910312 CA308256 BI908079

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)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TAGCCCCCTG

About this image

TNF expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Early Embryo (Zygote)

Early Embryo

Blood

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

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

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TNF Browse OriGene validated miRNA SYBR primer pairs
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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TNF

(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 2/8 species (see all 8) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
lizard (Anolis carolinensis)	Reptilia	TNF⁶	--	36(a)	1 ↔ 1	2(195687375-195691887)
zebrafish (Danio rerio)	Actinopterygii	tnfa⁶ tnfb⁶	tumor necrosis factor a (TNF superfamily, member 2... tumor necrosis factor b (TNF superfamily, member 2...	26(a) 21(a)	many ↔ many many ↔ many	19(27505097-27509684) 15(33995840-33998916)

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, UniProtKB, 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]

SNP ID	Valid	Clinical significance	Chr 6 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs2736196^1,2	C,H	--	31329389(-)	`ATGCTG/TGTTTC`	1	--	us2k¹		4		NS EA	406
rs2736195^1,2	C	--	31329425(-)	`AGGCCC/TTCTTC`	1	--	us2k¹		0	--	--	--	--
rs4248160^1,2	C,F,	--	31329427(+)	`AGAAGG/ACCTGC`	1	--	us2k¹		3		NS NA	332
rs4248162^1,2	C,F	--	31329503(+)	`GCTACC/ACCCAC`	1	--	us2k¹		2		NS	330
rs2857711^1,2	C	--	31329505(-)	`GGGTGC/GGGGTA`	1	--	us2k¹		0	--	--	--	--
rs3093548^1,2	C	--	31329554(+)	`AGCTCC/TTTCTC`	1	--	us2k¹		2		NS	94
rs4248163^1,2	C,F	--	31329562(+)	`CTCCCC/GGCAGG`	1	--	us2k¹		2		NS	328
rs1800750^1,2	C,F,H,	--	31329697(+)	`TGGAAG/ATTAGA`	1	--	us2k¹		27		NS MN EA NA	3174
rs4987027^1,2	C,	--	31329828(+)	`CCCCTA/C/TRGAAT`	1	--	us2k¹		5		MN	400
rs673^1,2	C,F,	--	31329829(+)	`CCCTCG/AGAATC`	1	--	us2k¹		20		NS MN NA WA	1862

HapMap Linkage Disequilibrium report for TNF (31543344 - 31546113 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for TNF: --
Human Gene Mutation Database (HGMD): TNF

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TNF

DNA2.0 Custom Variant and Variant Library Synthesis for TNF

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TNF for disorders           About GeneDecksing

OMIM gene information: 191160
OMIM disorders: 611162  600807  157300
UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375

Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is

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

rheumatoidlike 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)

20/783 diseases for TNF (see all 783): About MalaCards

charcot-marie-tooth neuropathy charcot-marie-tooth neuropathy type 2 new daily-persistent headache charcot-marie-tooth neuropathy type 2a

periodic fever, aphthous stomatitis, pharyngitis and adenitis punctate inner choroidopathy insulin resistance carotid intimal medial thickness

migraine without aura crimean-congo hemorrhagic fever open-angle glaucoma lambert-eaton myasthenic syndrome

post-transplant lymphoproliferative disease graft versus host disease monoclonal gammopathy of uncertain significance maternally inherited leigh syndrome

perinatal necrotizing enterocolitis alpha 1-antitrypsin deficiency benign migratory glossitis weill-marchesani syndrome

14 diseases from the University of Copenhagen DISEASES database for TNF:

Rheumatoid arthritis Inflammatory bowel disease Hypersensitivity reaction type II disease Cancer

Malaria Connective tissue disease Ankylosing spondylitis Psoriatic arthritis

Psoriasis Tuberculosis Vascular disease Multiple sclerosis

Asthma Peritonitis

10/96 Novoseek 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 16820):
(articles sorted by number of sources associating them with TNF)

Utopia: connect your pdf to the dynamic
world of online information

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)
Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. (PubMed id 6392892)^{1, 2, 3} Pennica D.... Goeddel D.V. (1984)
TNF-alpha promoter, Nod2 and toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. (PubMed id 15016407)^{1, 4, 9} Schippers E.F....van Dissel J.T. (2004)
TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study. (PubMed id 15526005)^{1, 4, 9} Gordon A.C....Hinds C.J. (2004)
Relation of tumor necrosis factor (TNF) gene polymorphisms with serum concentrations and in vitro production of TNF-alpha and interleukin-8 in heavy drinkers. (PubMed id 15902922)^{1, 4, 9} Gonzalez-Quintela A....Perez L.F. (2004)
Genetic variation in the stress protein hsp70-2 gene is highly associated with obesity. (PubMed id 11319647)^{1, 4, 9} Chouchane L....Strosberg A.D. (2001)
Polymorphism of cytokine genes (TGF-beta1, IFN-gamma, IL-6, IL-10, and TNF-alpha) in patients with chronic pancreatitis. (PubMed id 15841043)^{1, 4, 9} Bendicho M.T....Lemaire D.C. (2005)
-238 and +489 TNF-alpha along with TNF-RII gene polymorphisms associate with the diffuse phenotype in patients with Systemic Sclerosis. (PubMed id 15585313)^{1, 4, 9} Tolusso B....Ferraccioli G. (2005)
[The associations of the single nucleotide polymorphisms on TNF and CD14 promoters with the mortality of infection, systematic inflammatory response syndromec and sepsis in surgical patients] (PubMed id 14720421)^{1, 4, 9} Yu B.J....Tang X.M. (2003)
Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. (PubMed id 12828656)^{1, 4, 9} Fassmann A....Vanek J. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
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

Name	Description
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-SNPs	http://egp.gs.washington.edu/data/tnf/
SeattleSNPs	http://pga.gs.washington.edu/data/tnf/
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF

Intellectual Property for TNF gene
(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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In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TNF
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tumor necrosis factor

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Spondylitis Ankylosing
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TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PERIODIC SYNDROME
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tumor necrosis factor

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