Harmonizome 3.0

tumor necrosis factor

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, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020]

TNF receptor-associated factor 4 pseudogene

TNF receptor-associated factor 6

TNF receptor-associated factor 1

The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with inhibitor-of-apoptosis proteins (IAPs), and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

TNF receptor-associated factor 2

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]

TNF receptor-associated factor 3

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5. [provided by RefSeq, Jul 2020]

TNF receptor-associated factor 4

This gene encodes a member of the TNF receptor associated factor (TRAF) family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. The encoded protein has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1), and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

TNF receptor-associated factor 5

The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

TNF receptor-associated factor 6, E3 ubiquitin protein ligase

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain and mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. The protein encoded by this gene is a key molecule in antiviral innate and antigen-specific immune responses. [provided by RefSeq, Nov 2021]

TNF receptor-associated factor 7, E3 ubiquitin protein ligase

Tumor necrosis factor (TNF; see MIM 191160) receptor-associated factors, such as TRAF7, are signal transducers for members of the TNF receptor superfamily (see MIM 191190). TRAFs are composed of an N-terminal cysteine/histidine-rich region containing zinc RING and/or zinc finger motifs; a coiled-coil (leucine zipper) motif; and a homologous region that defines the TRAF family, the TRAF domain, which is involved in self-association and receptor binding.[supplied by OMIM, Apr 2004]

lipopolysaccharide-induced TNF factor

Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]

TNF receptor-associated factor 6 pseudogene 1

TNF and HNRNPL related immunoregulatory long non-coding RNA

TNF receptor-associated protein 1

This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TNF receptor-associated factor 7, E3 ubiquitin protein ligase pseudogene

CD40 molecule, TNF receptor superfamily member 5

This gene is a member of the TNF-receptor superfamily. The encoded protein is a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency type 3 (HIGM3). Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2014]

Fas ligand (TNF superfamily, member 6)

This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

lymphotoxin beta (TNF superfamily, member 3)

Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

C1q and TNF related 12

Predicted to enable hormone activity. Predicted to be involved in negative regulation of gluconeogenesis; positive regulation of D-glucose import; and positive regulation of insulin receptor signaling pathway. Predicted to act upstream of or within negative regulation of inflammatory response; positive regulation of cell communication; and regulation of glucose metabolic process. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Mar 2025]

TNF alpha induced protein 8 like 1

Enables identical protein binding activity. Predicted to be involved in negative regulation of TOR signaling. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Mar 2025]

TNF alpha induced protein 8 like 3

Predicted to enable phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Predicted to be involved in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate metabolic process; phospholipid transport; and positive regulation of ERK1 and ERK2 cascade. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]

TNF alpha induced protein 8 like 2

Predicted to be involved in negative regulation of T cell activation and negative regulation of inflammatory response. Predicted to be located in lysosome and nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Mar 2025]

From Phosphosite Textmining Biological Term Annotations

proteins co-occuring with the biological term tnf-alpha in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.

From DGIdb Drug Targets 2026

interacting proteins for the TNF-ALPHA drug from theDGIdb Drug Targets 2026 dataset.

From Biocarta Pathways

proteins participating in the tnf/stress related signaling pathway from the Biocarta Pathways dataset.

From Biocarta Pathways

proteins participating in the hiv-1 nef: negative effector of fas and tnf pathway from the Biocarta Pathways dataset.

From ClinVar Gene-Phenotype Associations

genes associated with the TNF receptor-associated periodic fever syndrome (TRAPS) phenotype from the curated ClinVar Gene-Phenotype Associations dataset.

From GAD Gene-Disease Associations

genes associated with the disease high tnf levels is not a risk factor for venous thromboem in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.

From GAD Gene-Disease Associations

genes associated with the disease arthritis, rheumatoid; rheumatoid arthritis; anti-tnf response in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.

From GAD Gene-Disease Associations

genes associated with the disease response to tnf antagonist treatment in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.

From GeneRIF Biological Term Annotations

genes co-occuring with the biological term tnf in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.

From Guide to Pharmacology Protein Ligands of Receptors

receptors of the TNF ligand (protein) from the curated Guide to Pharmacology Protein Ligands of Receptors dataset.

From GWAS Catalog SNP-Phenotype Associations

genes associated with the Response to TNF antagonist treatment phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.

From GWAS Catalog SNP-Phenotype Associations

genes associated with the Response to anti-TNF treatment in rheumatoid arthritis phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor family, RELT protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor TRAF protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 4 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 5 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 6 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 1 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 2 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the TNF receptor-associated factor 3 protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From Pathway Commons Protein-Protein Interactions

interacting proteins for TNF from the Pathway Commons Protein-Protein Interactions dataset.

From Phosphosite Textmining Biological Term Annotations

proteins co-occuring with the biological term tnf in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.

From PID Pathways

proteins participating in the TNF receptor signaling pathway pathway from the PID Pathways dataset.

From Reactome Pathways 2014

proteins participating in the TNF signaling pathway from the Reactome Pathways dataset.

From DisGeNET Gene-Disease Associations

genes associated with the disease Tnf Receptor-Associated Periodic Fever Syndrome (Traps) in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.

From DisGeNET Gene-Phenotype Associations

genes associated with the phenotype Tnf Receptor Binding, Altered in GWAS and other genetic association datasets from the DisGeNET Gene-Phenotype Associations dataset.

From WikiPathways Pathways 2024

proteins participating in the TNF related weak inducer of apoptosis TWEAK signaling pathway from the WikiPathways Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway pathway from the Reactome Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the TNF signaling pathway from the Reactome Pathways 2024 dataset.

From ClinVar Gene-Phenotype Associations 2025

genes associated with the TNF receptor-associated periodic fever syndrome phenotype from the curated ClinVar Gene-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to anti-TNF therapy in rheumatoid arthritis phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF inhibitor in rheumatoid arthritis (erythrocyte sedimentation rate) phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count) phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF inhibitor in rheumatoid arthritis (change in patient global heath assessment score) phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count) phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF inhibitor in rheumatoid arthritis (change in disease activity score) phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From GWAS Catalog SNP-Phenotype Associations 2025

genes associated with the Response to TNF antagonist treatment phenotype in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.

From KEGG Pathways 2026

proteins participating in the TNF signaling pathway pathway from the KEGG Pathways 2026 dataset.