FGFR3c P250R mutant binds to ligand with enhanced affinity

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
FGFR3 P350R is associated with the development of Muenke syndrome, a milder craniosynostotic condition than Apert Syndrome (Bellus, 1996; Reardon, 1997). This mutation, which falls in the highly conserved Ser-Pro dipeptide in the IgII-IgIII linker, has been shown to increase the affinity of the receptor for its natural ligands, particularly for FGF9 (Ibrahimi, 2004a), without expanding the ligand-binding range of the receptor. This difference, compared to the paralogous FGFR2 S252W and P253R mutations, which bind an expanded range of ligands, is thought to account for the milder phenotype of Muenke Syndrome (Yu, 2000; Ibrahimi, 2004a, b).
Literature References
PubMed ID Title Journal Year
9279753 Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis

Rutland, P, Hall, CM, Winter, RM, Hayward, R, Pulleyn, LJ, Dean, JC, Nevin, NC, Baraister, M, Evans, RD, Jones, BM, Reardon, W, Malcolm, S, Wilkes, D

J Med Genet 1997
15282208 Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities

Eliseenkova, AV, Linhardt, RJ, Itoh, N, Zhang, F, Mohammadi, M, Ibrahimi, OA

Hum Mol Genet 2004
8841188 Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes

Francomano, CA, Clarke, LA, Bellus, GA, Zackai, EH, Muenke, M, Szabo, J, Gaudenz, K

Nat Genet 1996
14613973 Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity

Eliseenkova, AV, Linhardt, RJ, Zhang, F, Mohammadi, M, Ibrahimi, OA

Hum Mol Genet 2004
11121055 Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome

Herr, AB, Ornitz, DM, Yu, K, Waksman, G

Proc Natl Acad Sci U S A 2000
Functional status

Gain of function of FGFR3c P250R [plasma membrane]

Disease Entity
Name Identifier Synonyms
craniosynostosis DOID:2340 Premature closure of cranial sutures
acrocephalosyndactylia DOID:12960 Apert syndrome
Cite Us!