FGFR1
Chr 8ADfibroblast growth factor receptor 1
Also known as: BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1, FLG, FLT-2
The encoded fibroblast growth factor receptor 1 protein contains an extracellular domain that binds fibroblast growth factors and an intracellular tyrosine kinase domain that activates downstream signaling cascades controlling cell proliferation and differentiation during development. Autosomal dominant mutations cause multiple craniosynostosis syndromes including Pfeiffer syndrome, Jackson-Weiss syndrome, and osteoglophonic dysplasia, as well as Kallmann syndrome with hypogonadotropic hypogonadism and anosmia. The pathogenic mechanism involves gain-of-function mutations that lead to premature suture fusion in craniosynostosis or loss-of-function mutations affecting hypothalamic-pituitary-gonadal axis development in Kallmann syndrome.
Definitive — sufficient evidence for diagnostic panels
3 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, gain-of-function and dominant-negative). 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
FGFR1 · 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
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGA Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody
NOT YET 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 RECRUITINGSafety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations
RECRUITINGTAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
RECRUITINGASO Treatment for Syndromic Craniosynostoses
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools