FGFR3

About FGFR3

FGFR3 on chromosome 4p16.3 encodes fibroblast growth factor receptor 3, a receptor tyrosine kinase that acts as a brake on the growth of cartilage in the growth plates of long bones. Gain of function variants overactivate this brake. A single recurrent variant, G380R, causes almost all cases of achondroplasia, the most common form of skeletal dysplasia with disproportionate short stature, and most cases arise as new variants, more often with advancing paternal age. Other FGFR3 variants cause the milder hypochondroplasia and the severe thanatophoric dysplasia, as well as some craniosynostosis syndromes. Somatic FGFR3 mutations are common in bladder cancer, and erdafitinib, an FGFR inhibitor, is approved for some urothelial cancers with these changes. Vosoritide, a C type natriuretic peptide analogue that counteracts FGFR3 signaling, was approved in 2021 to increase growth in children with achondroplasia.