FGFR2
Chr 10ADfibroblast growth factor receptor 2
Also known as: BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS
This gene encodes a transmembrane tyrosine kinase receptor that binds fibroblast growth factors and activates downstream signaling cascades that regulate cell proliferation and differentiation. Mutations cause multiple autosomal dominant craniosynostosis syndromes including Apert, Crouzon, Pfeiffer, Jackson-Weiss, Beare-Stevenson, and Saethre-Chotzen syndromes, as well as other skeletal dysplasias like Antley-Bixler syndrome and bent bone dysplasia. The pathogenic mutations typically result in gain-of-function effects that lead to premature fusion of cranial sutures and associated craniofacial abnormalities.
Definitive — sufficient evidence for diagnostic panels
6 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FGFR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Marker Assisted Selective ThErapy in Rare Cancers: Knowledge Database Establishing registrY Asia
RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGA Post-marketing Observational Study of Tasfygo in Participants With Unresectable Biliary Tract Cancer With Fibroblast Growth Factor Receptor 2 (FGFR2) Fusion Gene Positivity Who Progressed After Chemotherapy
RECRUITINGA Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors
ACTIVE NOT RECRUITINGTesting Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGA Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement
RECRUITINGBiomoleculars Markers of Sensitivity to Pre- and Post-operative Chemotherapy of Gastric and Cardia Adenocarcinomas: a Pilot Study
RECRUITINGEfficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NOT YET RECRUITINGSafety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations
RECRUITINGA Phase 2 Clinical Study of ABSK061 and ABSK043
RECRUITINGStudy of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement
RECRUITINGExternal Resources
Links to major genomics databases and tools