FGFR4
Chr 5fibroblast growth factor receptor 4
Also known as: CD334, JTK2, TKF
The FGFR4 protein is a tyrosine kinase that functions as a cell surface receptor for fibroblast growth factors and regulates cell proliferation, differentiation, migration, lipid metabolism, bile acid biosynthesis, and phosphate homeostasis. Mutations in this gene are associated with cancer progression and metastasis through aberrant signaling pathways. This gene shows low constraint against loss-of-function variants (LOEUF 0.87), suggesting tolerance to protein-truncating mutations.
Primary Disease Associations & Inheritance
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
226 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 | 0 | 56 | 0 | 56 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 1 | 98 | 4 | 1 | 104 |
Likely Benign | 0 | 5 | 3 | 9 | 17 |
Benign | 0 | 3 | 3 | 4 | 10 |
Conflicting | — | 1 | |||
| Total | 1 | 106 | 70 | 14 | 192 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FGFR4 · 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
Targeted 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 Modular Multi-Basket Trial to Improve Personalized Medicine in Cancer Patients (Basket of Baskets)
RECRUITINGSafety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations
RECRUITINGExternal Resources
Links to major genomics databases and tools