Protein / target

Tumor necrosis factor

TNFP01375Homo sapiensSwiss-Prot
UniProt: P01375Ensembl: ENSG00000204490HGNC: HGNC:11892NCBI Gene: 7124
30
Clinical trials
1
Drugs targeting

Protein at a glance

Biological role

Transcription cis-regulatory region binding

Primary system

Immune system

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

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. 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

Cell membraneMembraneSecreted
Domains and Gene Ontology detail (165)

Domains & features

THD

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

233 aa · 26 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GO · ReactomeTranscriptional regulationGO · ReactomeKinase signallingUniProt · GOApoptosis & cell deathGOSynaptic signallingGOCell adhesionGO
View supporting evidence

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

Kinase signalling

  • ·Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macro…
  • ·negative regulation of oxidative phosphorylation
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Apoptosis & cell death

  • ·endothelial cell apoptotic process
  • ·positive regulation of apoptotic process
  • ·positive regulation of neuron apoptotic process
  • ·positive regulation of programmed cell death

Synaptic signalling

  • ·positive regulation of synaptic transmission
  • ·regulation of synapse organization
  • ·regulation of synaptic transmission, glutamatergic

Cell adhesion

  • ·negative regulation of bicellular tight junction assembly
  • ·positive regulation of cell adhesion
  • ·positive regulation of heterotypic cell-cell adhesion
View underlying pathways (11)
Transcriptional regulation of white adipocyte differentiation
TNFR1-induced proapoptotic signaling
Regulation of TNFR1 signaling
TNFR1-induced NF-kappa-B signaling pathway
TNFR1-mediated ceramide production
TNFR2 non-canonical NF-kB pathway
Interleukin-10 signaling
Interleukin-4 and Interleukin-13 signaling
TNF signaling
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)
Differentiation of Circulating Monocytes

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

TAB2NFKB1TRAF2RIPK1CHUKTRADDIKBKBBIRC2CASP8MAP3K7TNF

10 strongest partners — larger node and heavier line mean higher confidence

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

golimumab
Narrow target profileInhibitor

TNF-alpha inhibitor

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

A Phase 2a Open-Label Study to Evaluate Prediction of Response to Golimumab Using a Transcriptomic Profile in Subjects With Moderately to Severely Active Ulcerative ColitisPHASE2

COMPLETED · via golimumab · NCT01988961

Pilot Study to Evaluate the Efficacy of Golimumab for Induction and Maintenance of Clinical and Endoscopic Remission in Patients With Steroid-dependent Ulcerative ColitisPHASE4

UNKNOWN · via golimumab · NCT02412085

Targeting Beta Cell Dysfunction in Longstanding T1DEARLY_PHASE1

COMPLETED · via golimumab · NCT03632759

Tumor Necrosis Factor Blocker (Anti-TNFα) to Delay or Prevent Progression to Stage 3 T1DPHASE2

WITHDRAWN · via golimumab · NCT04729296

A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα Antibody, in Pediatric Subjects With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate TherapyPHASE3

COMPLETED · via golimumab · NCT02277444

A Phase 2, Multicenter, Randomized, Double-Blind, Parallel-group, Placebo-controlled Study Evaluating the Safety and Efficacy of Treatment With Ustekinumab or Golimumab in Subjects With Chronic SarcoidosisPHASE2

COMPLETED · via golimumab · NCT00955279

Show remaining trials (24)
A First-in-human, Randomized, Parallel Group, Double-blind, 3-arm Study to Investigate the Comparative PK, Safety, and Tolerability Between Subcutaneous AVT05, US-licensed Simponi®, and EU-approved Simponi® in Healthy Adult ParticipantsPHASE1

COMPLETED · via golimumab · NCT05632211

Open-label, Randomized Controlled Trial Comparing Tocilizumab to Anti-TNF Treatment and Discovery of Biomarkers for Treatment Selection in Rheumatoid Arthritis Patients With Inadequate Response to a First Anti-TNFPHASE4

TERMINATED · via golimumab · NCT03100253

Adaptive Platform Trial to Delay Progression From Normoglycemia to Dysglycemia in Presymptomatic Type 1 Diabetes: Golimumab SubstudyPHASE2

NOT_YET_RECRUITING · via golimumab · NCT07683026

A Randomized, Open-label Study to Evaluate the Pharmacokinetics of a Single Subcutaneous Administration of 50 mg or 100 mg Golimumab in a Pre-filled Syringe Formulation to Healthy Male Chinese SubjectsPHASE1

COMPLETED · via golimumab · NCT01288157

Treatment of Rheumatoid Arthritis With Disease-modifying Antirheumatic Drugs (DMARDs): Predictors of ResponsePHASE3

RECRUITING · via golimumab · NCT03414502

Safety and Efficacy of Intratympanically Delivered Golimumab for Stabilization of Hearing in Patients With Autoimmune Inner Ear Disease: An Open-label Proof-of-concept Clinical TrialPHASE1/PHASE2

TERMINATED · via golimumab · NCT01526174

A Phase 3 Randomized, Open-Label Study to Assess the Efficacy, Safety, and Pharmacokinetics of Golimumab Treatment, a Human Anti-TNFα Monoclonal Antibody, Administered Subcutaneously in Pediatric Participants With Moderately to Severely Active Ulcerative ColitisPHASE3

ACTIVE_NOT_RECRUITING · via golimumab · NCT03596645

A Phase 2 Exploratory Study of Mavrilimumab Versus Anti-tumor Necrosis Factor in Subjects With Rheumatoid ArthritisPHASE2

COMPLETED · via golimumab · NCT01715896

COmparison of the Effect of Treatment With NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of StrUctural Damage in the Spine Over Two Years in Patients With ankyLosing Spondylitis: a Randomized Controlled Multicentre TrialPHASE4

COMPLETED · via golimumab · NCT02758782

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFα Monoclonal Antibody, Administered Intravenously, in Subjects With Active Psoriatic ArthritisPHASE3

COMPLETED · via golimumab · NCT02181673

A Pilot Study to Evaluate the Utility of Thermography in Assessing Response to Golimumab Treatment in Psoriatic ArthritisNA

TERMINATED · via golimumab · NCT02841176

GLM Dose Optimisation to Adequate Levels to Achieve Response in Colitis (GOAL-ARC). A Nationwide Multi-centred Randomised Controlled Trial (RCT) Investigating the Use of GLM Dose Adjustment in Ulcerative Colitis (UC).PHASE4

UNKNOWN · via golimumab · NCT02687724

A Research Study to Bank Samples for Future Evaluation to Identify Biomarkers That Predispose Crohn's Disease and Ulcerative Colitis Patients to Develop Hepatosplenic T-Cell Lymphoma (HSTCL)PHASE4

COMPLETED · via golimumab · NCT01804166

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate TherapyPHASE3

COMPLETED · via golimumab · NCT00973479

An Investigator-initiated Double-blind, Parallel-group Randomised Controlled Trial of GOLimumab and Methotrexate Versus Methotrexate in Very Early PsA Using Clinical and Whole Body MRI Outcomes: the GOLMePsA Study.PHASE3

COMPLETED · via golimumab · NCT04108468

A Randomized, Double-blind, Dose-ranging Trial of CNTO 148 Subcutaneous Injection Compared With Placebo in Subjects With Active Rheumatoid Arthritis Despite Treatment With MethotrexatePHASE2

COMPLETED · via golimumab · NCT00207714

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously in Subjects With Active Psoriatic ArthritisPHASE3

COMPLETED · via golimumab · NCT00265096

A Phase-IV, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of Golimumab (MK-8259 [SCH 900259]) After Treatment Withdrawal, Compared With Continued Treatment (Either Full- or Reduced-Treatment Regimen), In Subjects With Non-Radiographic Axial SpondyloarthritisPHASE4

COMPLETED · via golimumab · NCT03253796

Pharmacokinetic and Pharmacodynamic Study of Golimumab in Ulcerative Colitis (UC) Patients With Loss of Response (LOR) Followed by Dose OptimizationPHASE2

COMPLETED · via golimumab · NCT03182166

A Phase 1b Open-Label Study to Assess the Safety and Pharmacokinetics of Subcutaneously Administered Golimumab, a Human Anti-TNFα Antibody, in Pediatric Subjects With Moderately to Severely Active Ulcerative ColitisPHASE1

COMPLETED · via golimumab · NCT01900574

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Subjects With Active Radiographic Axial SpondyloarthritisPHASE3

TERMINATED · via golimumab · NCT02438787

A Phase 2a, Multicenter, Randomized, Double-blind Study Evaluating the Efficacy and Safety of Subcutaneously Administered Guselkumab and Golimumab Combination Therapy in Participants With Active Psoriatic ArthritisPHASE2

COMPLETED · via golimumab · NCT05071664

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Golimumab in the Treatment of Chinese Subjects With Ankylosing SpondylitisPHASE3

COMPLETED · via golimumab · NCT01248793

A Randomized, Double-blind, Placebo-controlled Trial of Golimumab+Methotrexate Versus Methotrexate Alone in Methotrexate-naïve Patients With Psoriatic ArthritisPHASE3

COMPLETED · via golimumab · NCT01871649

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Regulatory approval2026-02-10

    Approval: Gotenfia (EMA)

    ema · regulatory · ema · via golimumab

  2. Regulatory approval2025-11-17

    Approval: Gobivaz (EMA)

    ema · regulatory · ema · via golimumab

  3. New publication2023-11-01
    Efficacy and safety of golimumab in patients with non-radiographic axial spondyloarthritis: a withdrawal and retreatment study (GO-BACK).

    Rheumatology (Oxford, England) · 2023 · 8 citations · Europe PMC · via golimumab

  4. New publication2019-10-01
    Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study.

    Journal of Crohn's & colitis · 2019 · 14 citations · Europe PMC · via golimumab

  5. New publication2019-08-30
    Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab.

    Therapeutic advances in gastroenterology · 2019 · 6 citations · Europe PMC · via golimumab

  6. New publication2017-08-01
    Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review.

    BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2017 · 231 citations · Europe PMC · via golimumab

  7. New publication2015-10-01
    A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis.

    Arthritis & rheumatology (Hoboken, N.J.) · 2015 · 168 citations · Europe PMC · via golimumab

  8. New publication2013-06-05
    Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs: results of the GO-MORE study.

    Annals of the rheumatic diseases · 2014 · 15 citations · Europe PMC · via golimumab

  9. Regulatory approval2009-10-01

    Approval: Simponi (EMA)

    ema · regulatory · ema · via golimumab

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.