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Protein / target

Fibroblast growth factor receptor 4

Encoded byFGFR4P22455Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Fibroblast growth factor receptor

Primary biology

FGFR growth-factor signalling

Strongest disease association

Diabetes Mellitus, Type 2

Via encoding gene FGFR4 · Genetic evidence · score 0.89

Therapeutic position

Established drug target

Small molecules

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 overview

Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeos…

View complete UniProt function annotation

Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling

Subcellular location

Cell membraneEndosomeEndoplasmic reticulumSecreted
Domains and Gene Ontology detail (31)

Domains & features

Ig-like C2-type 1Ig-like C2-type 2Ig-like C2-type 3Protein kinase

Gene Ontology

  • Cendoplasmic reticulum
  • Cendosome
  • Cextracellular region
  • CGolgi apparatus
  • Cplasma membrane
  • Creceptor complex
  • Ctransport vesicle
  • FATP binding
  • Ffibroblast growth factor binding
  • Ffibroblast growth factor receptor activity
  • Fheparin binding
  • Pcell migration

802 aa · 88 kDa · 2 isoforms

Biological roles

Reactome v97

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

Cell proliferation & survivalUniProt · GO · ReactomeGrowth-factor signallingUniProt · GOLipid & lipoprotein metabolismGOCell migrationGOOncogenic signallingReactomeProteolysisUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth facto…
  • ·positive regulation of cell population proliferation
  • ·PIP3 activates AKT signaling
  • ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Growth-factor signalling

  • ·Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth facto…
  • ·fibroblast growth factor binding
  • ·fibroblast growth factor receptor activity
  • ·fibroblast growth factor receptor signaling pathway

Lipid & lipoprotein metabolism

  • ·cholesterol homeostasis
  • ·regulation of lipid metabolic process

Cell migration

  • ·cell migration

Oncogenic signalling

  • ·Constitutive Signaling by Aberrant PI3K in Cancer

Proteolysis

  • ·Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth facto…
  • ·positive regulation of proteolysis
View underlying pathways (14)

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.

FGF1FGF19KLBFGF2FGF4FGF6FGF9FGF8FGF5FGF18FGFR4

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.

Approved medicines with mapped indications

2 medicines · 4 areas

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.

Carcinoma, Transitional Cell1 medicine
Cholangiocarcinoma1 medicine
Urinary Bladder Neoplasms1 medicine
Broader indication categories (1)
Neoplasms2 medicines

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

6 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

erdafitinib
ApprovedInhibitor

Fibroblast growth factor receptor inhibitor

Indicated for Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Neoplasms

Acts on a complex — shared with FGFR3, FGFR1, FGFR2 · 1 of 4 recorded protein targets

futibatinib
ApprovedInhibitor

Fibroblast growth factor receptor inhibitor

Indicated for Cholangiocarcinoma, Neoplasms

Acts on a complex — shared with FGFR3, FGFR1, FGFR2 · 1 of 4 recorded protein targets

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

Translational evidence

Open Targets 26

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 FGFR4

Gene-level evidence surfaced through the gene FGFR4that 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.

Diabetes Mellitus, Type 2
0.91Well supported

Genetic evidence dominant · Open Targets 0.57

Neoplasms
0.87Well supported

Clinical evidence dominant · Open Targets 0.73

Carcinoma, Non-Small-Cell Lung
0.77Well supported

Clinical evidence dominant · Open Targets 0.58

Urothelial carcinoma
0.77Well supported

Clinical evidence dominant · Open Targets 0.61

Idiopathic Pulmonary Fibrosis
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

View evidence synthesis (5)
Diabetes Mellitus, Type 2Well supported
0.91
agreement 0.801.00
Genetic85%Clinical11%Literature4%

Open Targets aggregate 0.57 · 3 independent evidence families

NeoplasmsWell supported
0.87
agreement 0.770.97
Clinical47%Pathway27%Genetic17%Literature10%

Open Targets aggregate 0.73 · 4 independent evidence families

Carcinoma, Non-Small-Cell LungWell supported
0.77
agreement 0.660.88
Clinical57%Somatic mutation28%Literature11%RNA expression4%

Open Targets aggregate 0.58 · 4 independent evidence families

Urothelial carcinomaWell supported
0.77
agreement 0.640.89
Clinical69%Somatic mutation31%

Open Targets aggregate 0.61 · 2 independent evidence families

Idiopathic Pulmonary FibrosisModerately supported
0.73
agreement 0.570.88
Clinical98%Literature2%

Open Targets aggregate 0.59 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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.

Show all associations
Neoplasms0.73
Urothelial carcinoma0.61
Rhabdomyosarcoma0.60
Idiopathic Pulmonary Fibrosis0.59
Cholangiocarcinoma0.58
Carcinoma, Non-Small-Cell Lung0.58
Bone development disease0.57
Diabetes Mellitus, Type 20.57

Drug development

17 compounds recorded · 6 approved · 11 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ORANTINIBPhase 3
ERDAFITINIBApproval
NINTEDANIB ESYLATEApproval
FEXAGRATINIBPhase 2
DERAZANTINIBPhase 3
INFIGRATINIBApproval
NINTEDANIBApproval
ENMD-981693Phase 2
BRIVANIBPhase 3
FUTIBATINIBApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via erdafitinib · NCT03155620

RECRUITING · via futibatinib · NCT02693535

ACTIVE_NOT_RECRUITING · via erdafitinib · NCT02465060

TERMINATED · via futibatinib · NCT04189445

ClinicalTrials.gov via the drug-target graph.

What's happening now

4

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 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.

  1. Regulatory approval2024-08-22

    Approval: Balversa (EMA)

    ema · regulatory · ema · via erdafitinib

  2. Regulatory approval2023-07-04

    Approval: Lytgobi (EMA)

    ema · regulatory · ema · via futibatinib

  3. New publication2023-01-01
    Futibatinib for <i>FGFR2</i>-Rearranged Intrahepatic Cholangiocarcinoma.

    The New England journal of medicine · 2023 · 420 citations · Europe PMC · via futibatinib

  4. New publication2019-07-01
    Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.

    The New England journal of medicine · 2019 · 1,006 citations · Europe PMC · via erdafitinib

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.