FGFR4
FGFR4 (Fibroblast growth factor receptor 4) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Sarcomas, Biliary tract cancer, Colorectal cancer and 5 more.
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 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.
CIViC holds 12 clinical evidence items and 0 assertions across 6 variants, naming FGF/VEGF Receptor Tyrosine Kinase Inhibitor, PD173074, Erlotinib, Sorafenib and Ponatinib and others. Open Targets scores its association with cancer at 0.84 (direct and indirect evidence; datatypes clinical 0.98, affected pathway 0.90, literature 0.99, genetic association 0.00, somatic mutation 0.87). IntOGen calls it a driver in 3 cohorts (0 activating, 3 loss-of-function), covering Glioblastoma Multiforme, Endometrial Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · FGFR4 (Fibroblast growth factor receptor 4) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Sarcomas, Biliary tract cancer, Colorectal cancer and 5 more.
- 1 · What it is
FGFR4 (Fibroblast growth factor receptor 4) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Sarcomas, Biliary tract cancer, Colorectal cancer and 5 more.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at FGFR4 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:3691 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P22455 (protein name, function text, keywords and locations (REST API)); CIViC gene FGFR4 (12 evidence items, 0 assertions, 6 variants; diseases: Lung Adenocarcinoma, Rhabdomyosarcoma, Ovarian Cancer, Stomach Cancer, Ewing Sarcoma and 4 more (GraphQL API, CC0)); Open Targets ENSG00000160867 (association with cancer (MONDO_0004992) 0.84; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.61, colorectal cancer 0.64, gastric cancer 0.51, cholangiocarcinoma 0.59, urinary bladder cancer 0.57, melanoma 0.60 (GraphQL API, CC0)); IntOGen FGFR4 (driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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 signalling cascades. Activation of PLCG1 leads to the production of the cellular signalling 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 signalling pathway, as well as of the AKT1 signalling pathway. Location: Cell membrane; Endosome; Endoplasmic reticulum; Secreted (UniProt). Locus 5q35.2 (HGNC).
- Sarcomas: Open Targets association 0.69 with sarcoma (MONDO_0005089)
- Biliary tract cancer: Open Targets association 0.68 with biliary tract cancer (MONDO_0003060)
- Colorectal cancer: Open Targets association 0.64 with colorectal cancer (MONDO_0005575)
- Lung cancer: Open Targets association 0.62 with lung cancer (MONDO_0008903)
- Breast cancer: Open Targets association 0.61 with breast cancer (MONDO_0007254)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.51 with gastric cancer (MONDO_0001056); CIViC evidence names this disease
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.98; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 12 clinical evidence items on its variants. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Alveolar Rhabdomyosarcoma.
Latest papers
topQuery for this target: (TITLE:"FGFR4" OR ABSTRACT:"FGFR4" OR TITLE:"fibroblast growth factor receptor 4" OR ABSTRACT:"fibroblast growth factor receptor 4" OR TITLE:"Fibroblast growth factor receptor 4" OR ABSTRACT:"Fibroblast growth factor receptor 4" OR TITLE:"JTK2" OR ABSTRACT:"JTK2" OR TITLE:"CD334" OR ABSTRACT:"CD334") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FGFR4, not a curated reading list.
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