Change‐of‐function fibroblast growth factor receptor 3 mutations causing skeletal dysplasias
4 affiliations
- 1Department of Materials Science and Engineering and Institute for NanoBioTechnology Johns Hopkins University Baltimore Maryland USA
- 2Department of Biology Faculty of Medicine Masaryk University Brno Czechia
- 3International Clinical Research Center St. Anne's University Hospital Brno Czechia
- 4Institute of Animal Physiology and Genetics of the Czech Academy of Sciences Brno Czechia
Abstract
Fibroblast growth factor receptor 3 (FGFR3) is a membrane protein that plays a critical role as a negative regulator in the growth and development of the skeletal system. Mutations in FGFR3 cause a range of skeletal dysplasias. The G380R mutation in FGFR3 causes achondroplasia (ACH), the most common form of human short‐limbed dwarfism, whereas the A391E mutation in FGFR3 causes Crouzon syndrome, a craniosynostosis characterized by premature fusion of sutures between the cranial bones, with acanthosis nigricans. Both mutations are considered “gain‐of‐function” and occur close to each other within the simple FGFR3 helix that spans the membrane. Yet, the two pathological phenotypes of ACH and Crouzon syndrome are distinctly different. Here, we show that FGFR3 engages in biased signaling. We further show that the G380R and A391E mutations do not simply amplify signaling but differentially reshape the FGFR3 signaling patterns. The data provide an explanation of the distinctly different phenotypes due to the two mutations and lead us to propose that the mutations are “change‐of‐function.”
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BibTeX
@article{roy2026changeoffunction,
title = {{Change‐of‐function fibroblast growth factor receptor 3 mutations causing skeletal dysplasias}},
author = {Tanaya Roy and Zuzana Feketova and Jiawei Liu and Pavel Krejci and Kalina Hristova},
journal = {Journal of cell communication and signaling},
year = {2026},
month = oct,
doi = {10.1002/ccs3.70119},
url = {https://europepmc.org/article/PMC/PMC13722780},
note = {CC BY},
}
RIS
TY - JOUR
TI - Change‐of‐function fibroblast growth factor receptor 3 mutations causing skeletal dysplasias
AU - Tanaya Roy
AU - Zuzana Feketova
AU - Jiawei Liu
AU - Pavel Krejci
AU - Kalina Hristova
PY - 2026
DA - 2026/10/30
JO - Journal of cell communication and signaling
DO - 10.1002/ccs3.70119
UR - https://europepmc.org/article/PMC/PMC13722780
AB - Fibroblast growth factor receptor 3 (FGFR3) is a membrane protein that plays a critical role as a negative regulator in the growth and development of the skeletal system. Mutations in FGFR3 cause a range of skeletal dysplasias. The G380R mutation in FGFR3 causes achondroplasia (ACH), the most common form of human short‐limbed dwarfism, whereas the A391E mutation in FGFR3 causes Crouzon syndrome, a craniosynostosis characterized by premature fusion of sutures between the cranial bones, with acanthosis nigricans. Both mutations are considered “gain‐of‐function” and occur close to each other within the simple FGFR3 helix that spans the membrane. Yet, the two pathological phenotypes of ACH and Crouzon syndrome are distinctly different. Here, we show that FGFR3 engages in biased signaling. We further show that the G380R and A391E mutations do not simply amplify signaling but differentially reshape the FGFR3 signaling patterns. The data provide an explanation of the distinctly different phenotypes due to the two mutations and lead us to propose that the mutations are “change‐of‐function.”
SN - 1873-9601
SN - 1873-961X
ER -