FGFR2
Chr 10ADfibroblast growth factor receptor 2
Also known as: BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]
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 — mechanism propensity
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.
References
ClinVar Variant Classifications
954 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 8 | 57 | 4 | 2 | 71 |
Likely Pathogenic | 5 | 55 | 1 | 0 | 61 |
VUS | 12 | 308 | 49 | 17 | 386 |
Likely Benign | 0 | 11 | 138 | 136 | 285 |
Benign | 0 | 1 | 70 | 4 | 75 |
Conflicting | — | 53 | |||
| Total | 25 | 432 | 262 | 159 | 931 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →48 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap FGFR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
FGFR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ASO Treatment for Syndromic Craniosynostoses
NOT YET RECRUITINGMarker Assisted Selective ThErapy in Rare Cancers: Knowledge Database Establishing registrY Asia
RECRUITINGA Phase 2 Clinical Study of ABSK061 and ABSK043
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 Phase II Nationwide, Fully Decentralized, Telemedicine Study of Pemigatinib in Adult Patients With Advanced or Metastatic Pancreatic Cancer With FGFR Genetic Alterations
RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGA Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors
ACTIVE NOT RECRUITINGBiomoleculars Markers of Sensitivity to Pre- and Post-operative Chemotherapy of Gastric and Cardia Adenocarcinomas: a Pilot Study
RECRUITINGStudy of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement
RECRUITINGA Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement
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 RECRUITINGEfficacy and Safety of 3D185 Monotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools