FGFR3 is one of 4 high affinity tyrosine kinase receptors for the fibroblast growth factor family of ligands. On ligand stimulation, FGFR3 undergoes dimerization and tyrosine autophosphorylation, resulting in cell proliferation or differentiation, , through the mitogen-activated protein kinase (MAPK) and phospholipase Cg signal transduction pathways. Some FGFR3 mutations are believed to result in ligand-independent activation of the receptor. However, FGFR3 F384L mutation is not associated with activation of FGFR and, in NIH-3T3 cells, it was demonstrated to be devoid of any transforming activity. In some cases, the possibility of FGFR3 variants being of germline origin, cannot be excluded. The FGFR3 F384L mutation has been reported as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134404/). Clinical correlation is recommended.
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