Gene: FGFR3

Alternate names for this Gene: ACH|CD333|CEK2|HSFGFR3EX|JTK4

Gene Summary: This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia.

Gene is located in Chromosome: 4

Location in Chromosome : 4p16.3

Description of this Gene: fibroblast growth factor receptor 3

Type of Gene: protein-coding

rs587779383 in FGFR3 gene and Acanthosis Nigricans PMID 17875876 2007 Familial acanthosis nigricans due to K650T FGFR3 mutation.

PMID 18000903 2007 Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.

rs121913105 in FGFR3 gene and Achondroplasia PMID 10611230 2000 The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.

PMID 12297284 2002 FGF receptors ubiquitylation: dependence on tyrosine kinase activity and role in downregulation.

PMID 7847369 1995 Achondroplasia is defined by recurrent G380R mutations of FGFR3.

PMID 8599935 1996 Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia.

PMID 8078586 1994 Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.

PMID 7758520 1995 A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

rs121913105 in FGFR3 gene and Achondroplasia, Severe, With Developmental Delay And Acanthosis Nigricans PMID 10053006 1999 We refer to the phenotype caused by the Lys650Met mutation as "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

rs121913482 in FGFR3 gene and Adenocarcinoma of lung (disorder) PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

rs3135890 in FGFR3 gene and Body Height PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs121913113 in FGFR3 gene and CATSHL syndrome PMID 17033969 2006 A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

rs121913116 in FGFR3 gene and CROUZON SYNDROME WITH ACANTHOSIS NIGRICANS (disorder) PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 7493034 1995 Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.

PMID 17935505 2007 The molecular abnormality associated with Crouzon syndrome with acanthosis nigricans (CAN) is a transition in the transmembrane domain of the FGFR3 gene that results in an Ala391Glu mutation.

PMID 18976668 2008 Pathogenic activation of receptor tyrosine kinases in mammalian membranes.

PMID 9857065 1998 Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signaling in PC12 cells. A model for the control of receptor tyrosine kinase activation.

PMID 21536014 2011 The A391E mutation enhances FGFR3 activation in the absence of ligand.

PMID 20199409 2010 Molecular tests identified the FGFR3 Ala391Glu substitution confirming the diagnosis of CAN.

rs121913480 in FGFR3 gene and Carcinoma PMID 15880580 2005 Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas.

PMID 10471491 1999 Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.

PMID 12009017 2002 Differential activation of cysteine-substitution mutants of fibroblast growth factor receptor 3 is determined by cysteine localization.

PMID 11429702 2001 Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations.

PMID 19165726 2009 The strong dimerization of the transmembrane domain of the fibroblast growth factor receptor (FGFR) is modulated by C-terminal juxtamembrane residues.

PMID 9857065 1998 Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signaling in PC12 cells. A model for the control of receptor tyrosine kinase activation.

rs121913479 in FGFR3 gene and Carcinoma of bladder PMID 19381019 2009 Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 20542753 2010 FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population.

rs121913105 in FGFR3 gene and Craniosynostosis PMID 26818779 2016 Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation.

PMID 11055896 2000 Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.

PMID 17875876 2007 Familial acanthosis nigricans due to K650T FGFR3 mutation.

PMID 25809207 2016 Familial hypochondroplasia and acanthosis nigricans with FGFR3 K650T mutation.

PMID 18583390 2008 Hypochondroplasia and Acanthosis nigricans: a new syndrome due to the p.Lys650Thr mutation in the fibroblast growth factor receptor 3 gene?

PMID 17033969 2006 A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.

PMID 27139183 2016 A second family with CATSHL syndrome: Confirmatory report of another unique FGFR3 syndrome.

PMID 11879084 2002 Clinical and biochemical findings of a patient with thanatophoric dysplasia type I: additional finding of dicarboxylic aciduria.

PMID 25606676 2015 Effect of thanatophoric dysplasia type I mutations on FGFR3 dimerization.

PMID 17384684 2007 Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer.

PMID 19749790 2009 Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner.

PMID 8589699 1995 Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.

PMID 11038465 2000 Sonographic and molecular diagnosis of thanatophoric dysplasia type I at 18 weeks of gestation.

PMID 19088846 2008 Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage.

PMID 24476948 2014 Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound.

PMID 28249712 2017 Genetically confirmed thanatophoric dysplasia with fibroblast growth factor receptor 3 mutation.

PMID 8845844 1996 Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).

PMID 20453470 2010 FGFR3 mutations and the skin: report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 25614871 2014 FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry.

PMID 21739570 2011 Achondroplasia with synostosis of multiple sutures.

PMID 22045636 2012 Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias.

PMID 25691418 2015 Association of achondroplasia with sagittal synostosis and scaphocephaly in two patients, an underestimated condition?

PMID 8723101 1996 Common mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism.

PMID 18976668 2008 Pathogenic activation of receptor tyrosine kinases in mammalian membranes.

PMID 20199409 2010 A newborn with acanthosis nigricans: can it be Crouzon syndrome with acanthosis nigricans?

PMID 21536014 2011 The A391E mutation enhances FGFR3 activation in the absence of ligand.

PMID 11426459 2001 Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3.

PMID 23437153 2013 Multiple consequences of a single amino acid pathogenic RTK mutation: the A391E mutation in FGFR3.

PMID 7493034 1995 Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.

PMID 8880573 1996 A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes Crouzon syndrome and acanthosis nigricans.

PMID 8589686 1995 A common FGFR3 gene mutation in hypochondroplasia.

PMID 9452043 1998 Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia.

PMID 23149434 2012 Hypochondroplasia in a child with 1620C>G (Asn540Lys) mutation in FGFR3.

PMID 23165795 2012 Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation.

PMID 7670477 1995 A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.

PMID 11754059 2001 Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype.

PMID 10360392 1999 Achondroplasia-hypochondroplasia complex in a newborn infant.

PMID 10094188 1999 Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.

PMID 15915095 2005 FGFR3 P250R mutation increases the risk of reoperation in apparent 'nonsyndromic' coronal craniosynostosis.

PMID 26740388 2016 Muenke syndrome: An international multicenter natural history study.

PMID 10861678 2000 Clinical findings in a patient with FGFR1 P252R mutation and comparison with the literature.

PMID 9042914 1997 A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

PMID 14613973 2004 Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively.

PMID 21510009 2011 Acanthosis nigricans and hypochondroplasia in a child with a K650Q mutation in FGFR3.

rs28933068 in FGFR3 gene and Dysmorphic features PMID 19449410 2009 Significant phenotypic variability of Muenke syndrome in identical twins.

PMID 17033969 2006 A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.

PMID 23740942 2013 New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.

PMID 17935505 2007 Crouzon with acanthosis nigricans. Further delineation of the syndrome.

PMID 15241680 2004 Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.

PMID 18328977 2008 Achondroplasia.

PMID 18344207 2008 A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003.

PMID 16501574 2006 Mutations in different components of FGF signaling in LADD syndrome.

PMID 19098178 2009 Brain and bone abnormalities of thanatophoric dwarfism.

PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.

PMID 18000976 2007 Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature.

PMID 23165795 2012 Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation.

PMID 9677066 1998 Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.

PMID 23378035 2013 Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism.

PMID 9950359 1999 Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.

PMID 9580776 1998 Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.

PMID 1956068 1991 The frequency of mental retardation in hypochondroplasia.

PMID 8845844 1996 Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).

PMID 10053006 1999 A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.

PMID 10602123 2000 Epidemiology and genetics of craniosynostosis.

PMID 17950653 2008 Achondroplasia: from genotype to phenotype.

PMID 9450868 1998 Comparison of clinical-radiological and molecular findings in hypochondroplasia.

PMID 7670477 1995 A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.

PMID 7847369 1995 Achondroplasia is defined by recurrent G380R mutations of FGFR3.

PMID 10777366 2000 Clinical and radiographic features of a family with hypochondroplasia owing to a novel Asn540Ser mutation in the fibroblast growth factor receptor 3 gene.

PMID 12707965 2003 Hypochondroplasia and stature within normal limits: another family with an Asn540Ser mutation in the fibroblast growth factor receptor 3 gene.

PMID 10213050 1999 "Let's call it ""Crouzonodermoskeletal syndrome"" so we won't be prisoners of our own conventional terminology."

PMID 4078868 1985 Phenotypic variation in LADD syndrome.

PMID 24864036 2014 A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.

PMID 25356217 2013 Growth and development in thanatophoric dysplasia - an update 25 years later.

PMID 25931420 2015 Experience of a skeletal dysplasia registry in Turkey: a five-years retrospective analysis.

PMID 22045636 2012 Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias.

PMID 26740388 2016 Muenke syndrome: An international multicenter natural history study.

PMID 26028288 2015 Executive Function and Adaptive Behavior in Muenke Syndrome.

rs121913116 in FGFR3 gene and Hypochondroplasia (disorder) PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 26380986 2015 Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders.

rs121913112 in FGFR3 gene and Lacrimoauriculodentodigital syndrome PMID 16501574 2006 Mutations in different components of FGF signaling in LADD syndrome.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

rs121913479 in FGFR3 gene and Malignant neoplasm of urinary bladder PMID 10471491 1999 Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.

PMID 11314002 2001 Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.

rs121913116 in FGFR3 gene and Muenke Syndrome PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 9042914 1997 A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

PMID 9950359 1999 Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.

PMID 11746040 2001 Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene.

rs121913482 in FGFR3 gene and Multiple Myeloma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121913485 in FGFR3 gene and Myeloproliferative disease PMID 21273588 2011 Constitutively active FGFR3 with Lys650Glu mutation enhances bortezomib sensitivity in plasma cell malignancy.

PMID 22869148 2013 Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance.

PMID 19331127 2009 Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells.

rs121913483 in FGFR3 gene and Papillary renal cell carcinoma, sporadic PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121913105 in FGFR3 gene and Seborrheic keratosis PMID 15772091 2005 Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.

rs121913482 in FGFR3 gene and Squamous cell carcinoma of lung PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121913482 in FGFR3 gene and Squamous cell carcinoma of the head and neck PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121913103 in FGFR3 gene and THANATOPHORIC DYSPLASIA, TYPE I (disorder) PMID 17509076 2007 The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor.

PMID 7647778 1995 Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.

PMID 8589699 1995 Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.

PMID 8845844 1996 Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).

PMID 9790257 1998 G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric dysplasia.

PMID 10671061 1998 Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia Type I. Mutations in brief no. 199. Online.

PMID 10360402 1999 Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.

PMID 7773297 1995 Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.

PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 9790257 1998 In conclusion, we have identified the G370C mutation in the FGFR3 gene in a Japanese TD1 patient.

PMID 7773297 1995 Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein.

PMID 7773297 1995 Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein.

rs78311289 in FGFR3 gene and Testicular Germ Cell Tumor PMID 19855393 2009 Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.

rs121913116 in FGFR3 gene and Thanatophoric dysplasia, type 2 PMID 16912704 2006 Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

PMID 7773297 1995 Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.

PMID 8754806 1996 Thanatophoric dysplasia type II (TDII) is a neonatal lethal skeletal dysplasia caused by a recurrent Lys-650-->Glu mutation within the highly conserved activation loop of the kinase domain of fibroblast growth factor receptor 3 (FGFR3).

PMID 12297284 2002 FGF receptors ubiquitylation: dependence on tyrosine kinase activity and role in downregulation.

rs121913482 in FGFR3 gene and Transitional cell carcinoma of bladder PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.