Protein / target
Tumor necrosis factor
Protein at a glance
Biological role
Transcription cis-regulatory region binding
Strongest disease association
Arthritis, Psoriatic
Therapeutic position
Established drug target
Research activity
Actively researched
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
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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. Up-regulates 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:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
Subcellular location
Domains and Gene Ontology detail (165)Hide
Domains & features
Gene Ontology
- Ccell surface
- Cexternal side of plasma membrane
- Cextracellular region
- Cextracellular space
- Cmembrane raft
- Cneuronal cell body
- Cphagocytic cup
- Cplasma membrane
- Crecycling endosome
- Fcytokine activity
- Fhistone H3K9ac reader activity
- Fidentical protein binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Cell migration
- ·negative regulation of blood vessel endothelial cell migration
- ·positive regulation of mononuclear cell migration
Excitatory neurotransmission
- ·regulation of synaptic transmission, glutamatergic
Cell-cycle regulation
- ·negative regulation of mitotic cell cycle
Immune signalling
- ·Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macro…
- ·cytokine activity
- ·antiviral innate immune response
- ·chronic inflammatory response to antigenic stimulus
Transcriptional regulation
- ·transcription cis-regulatory region binding
- ·negative regulation of DNA-templated transcription
- ·negative regulation of gene expression
- ·negative regulation of miRNA transcription
Apoptosis & cell death
- ·endothelial cell apoptotic process
- ·positive regulation of apoptotic process
- ·positive regulation of neuron apoptotic process
- ·positive regulation of programmed cell death
View underlying pathways (11)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
7 medicines meet Open Targets' target-level approved-medicine definition; the 5 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
TNF-alpha inhibitor
Indicated for Arthritis, Psoriatic, Arthritis, Rheumatoid, Colitis, Ulcerative, Immune System Diseases
TNF-alpha inhibitor
Indicated for Arthritis, Juvenile, Arthritis, Psoriatic, Arthritis, Rheumatoid, Immune System Diseases
TNF-alpha inhibitor
Indicated for Arthritis, Arthritis, Juvenile, Arthritis, Psoriatic, Arthritis, Rheumatoid
TNF-alpha inhibitor
Indicated for Arthritis, Psoriatic, Arthritis, Rheumatoid, Colitis, Ulcerative, Crohn's Disease
TNF-alpha inhibitor
Indicated for Arthritis, Psoriatic, Arthritis, Rheumatoid, Crohn's Disease, Immune System Diseases
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene TNF
Gene-level evidence surfaced through the gene TNFthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
14 compounds recorded · 7 approved · 7 in clinical development
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Emerging
Antibodies — Strong
Protein degraders — Emerging
Other modalities — Strong
View underlying tractability evidence (11)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 5 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Withdrawn from market
Market withdrawal: Inflectra (EMA)
- Regulatory approval
Approval: Gotenfia (EMA)
- Regulatory approval
Approval: Gobivaz (EMA)
- New publicationDivergent disruptive effects of soluble recombinant tau assemblies on synaptic plasticity in vivo.
- New publicationNeurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports.
- New publicationEfficacy and safety of golimumab in patients with non-radiographic axial spondyloarthritis: a withdrawal and retreatment study (GO-BACK).
- New publicationNew and Emerging Targeted Therapies for Hidradenitis Suppurativa.
- New publicationLong-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study.
- Regulatory approval
Approval: Hukyndra (EMA)
- Regulatory approval
Approval: Libmyris (EMA)
- New publicationThree-year efficacy and safety of certolizumab pegol for the treatment of plaque psoriasis: results from the randomized phase 3 CIMPACT trial.
- Regulatory approval
Approval: Yuflyma (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.