FGFR3
Chr 4ADARfibroblast growth factor receptor 3
Also known as: ACH, CD333, CEK2, HSFGFR3EX, JTK4
The protein functions as a fibroblast growth factor receptor with a cytoplasmic tyrosine kinase domain that binds acidic and basic fibroblast growth factors and regulates bone development and maintenance through downstream signaling cascades. Mutations cause multiple skeletal dysplasias including achondroplasia, hypochondroplasia, thanatophoric dysplasia types I and II, and craniosynostosis syndromes such as Muenke syndrome and Crouzon syndrome with acanthosis nigricans, inherited in autosomal dominant or autosomal recessive patterns. The pathogenic mechanism involves gain-of-function mutations that disrupt normal bone and cartilage development.
Definitive — sufficient evidence for diagnostic panels
7 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. 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.
ClinVar Variant Classifications
500 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 | 0 | 4 | 65 | 0 | 69 |
Likely Pathogenic | 1 | 3 | 3 | 0 | 7 |
VUS | 11 | 167 | 17 | 5 | 200 |
Likely Benign | 4 | 19 | 61 | 90 | 174 |
Benign | 0 | 1 | 13 | 6 | 20 |
Conflicting | — | 16 | |||
| Total | 16 | 194 | 159 | 101 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FGFR3 · 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)
RECRUITINGFeasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer
ACTIVE NOT RECRUITINGA Randomized Trial of Bicalutamide in Non-Muscle Invasive Bladder Cancer
RECRUITINGA Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors
ACTIVE NOT RECRUITINGA Study of Oral Erdafitinib in People With Recurrent Non-Invasive Bladder Cancer
ACTIVE NOT RECRUITINGPhase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma
RECRUITINGTesting Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
ACTIVE NOT RECRUITINGSafety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
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 RECRUITINGUsing Liquid Biopsy Testing to Identify, Monitor, Predict Recurrence in Urothelial Carcinoma
RECRUITINGFORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3
RECRUITINGSafety and Preliminary Anti-Tumor Activity of TYRA-300 in Advanced Urothelial Carcinoma and Other Solid Tumors With FGFR3 Gene Alterations
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools