Gene: FGFR1

Alternate names for this Gene: BFGFR|CD331|CEK|ECCL|FGFBR|FGFR-1|FLG|FLT-2|FLT2|HBGFR|HH2|HRTFDS|KAL2|N-SAM|OGD|bFGF-R-1

Gene Summary: The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists 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 both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

Gene is located in Chromosome: 8

Location in Chromosome : 8p11.23

Description of this Gene: fibroblast growth factor receptor 1

Type of Gene: protein-coding

rs1057519897 in FGFR1 gene and Acute lymphoblastic leukemia with lymphomatous features PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519897 in FGFR1 gene and Astrocytoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs3925 in FGFR1 gene and Body Height PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1057519898 in FGFR1 gene and Brain Stem Glioma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs57709857 in FGFR1 gene and Child Development Disorders, Pervasive PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs13317 in FGFR1 gene and Cleft Palate PMID 28232668 2017 Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.

rs13317 in FGFR1 gene and Cleft upper lip PMID 28232668 2017 Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.

rs869320694 in FGFR1 gene and Encephalocraniocutaneous lipomatosis PMID 19224897 2009 The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations.

PMID 26942290 2016 Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each.

rs1057519898 in FGFR1 gene and Gastric Adenocarcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519897 in FGFR1 gene and Glioblastoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs397515481 in FGFR1 gene and Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip-Palate PMID 24888332 2014 Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism.

PMID 23812909 2013 FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.

rs515726223 in FGFR1 gene and Hypogonadism, Isolated Hypogonadotropic PMID 24204987 2013 Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys.

rs515726224 in FGFR1 gene and Idiopathic hypogonadotropic hypogonadism PMID 24204987 2013 Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys.

rs121909633 in FGFR1 gene and Interfrontal craniofaciosynostosis PMID 11173846 2000 An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly.

rs121909627 in FGFR1 gene and JACKSON-WEISS SYNDROME PMID 10861678 2000 Clinical findings in a patient with FGFR1 P252R mutation and comparison with the literature.

rs121909627 in FGFR1 gene and Kallmann Syndrome 2 (disorder) PMID 7795583 1995 Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.

PMID 7874169 1994 A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.

PMID 24497711 2013 Mutational identification of fibroblast growth factor receptor 1 and fibroblast growth factor receptor 2 genes in craniosynostosis in Indian population.

PMID 25251565 2014 Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation.

PMID 24127277 2013 Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

PMID 14613973 2004 Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.

PMID 14564217 2003 The appearance of the feet in Pfeiffer syndrome caused by FGFR1 P252R mutation.

PMID 16957473 2006 FGFR1 Pfeiffer syndrome without craniosynostosis: an additional case report.

PMID 10942429 2000 A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures.

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

PMID 17154279 2007 Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis.

PMID 15845591 2005 Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report.

PMID 16882753 2006 Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia.

PMID 22927827 2012 SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.

PMID 15001591 2004 Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

PMID 19820032 2009 Impaired fibroblast growth factor receptor 1 signaling as a cause of normosmic idiopathic hypogonadotropic hypogonadism.

PMID 15605412 2005 Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).

PMID 12627230 2003 Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.

PMID 16764984 2006 Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.

PMID 26277103 2015 Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform.

PMID 16757108 2006 Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).

PMID 16606836 2006 Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism.

PMID 21700882 2011 Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism.

PMID 25077900 2014 The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients.

PMID 23643382 2013 Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.

PMID 28008864 2017 Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations.

PMID 28754744 2017 KLB, encoding β-Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism.

PMID 27502037 2016 Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

PMID 24204987 2013 Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys.

rs1057519897 in FGFR1 gene and Liver carcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519897 in FGFR1 gene and Medulloblastoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519898 in FGFR1 gene and NEUROBLASTOMA, SUSCEPTIBILITY TO PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121913472 in FGFR1 gene and Neoplasms PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

rs121909631 in FGFR1 gene and Osteoglophonic dwarfism PMID 15625620 2005 Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation.

PMID 16470795 2006 Extended mutational analyses of FGFR1 in osteoglophonic dysplasia.

rs121909627 in FGFR1 gene and Pfeiffer Syndrome PMID 24497711 2013 Mutational identification of fibroblast growth factor receptor 1 and fibroblast growth factor receptor 2 genes in craniosynostosis in Indian population.

PMID 24127277 2013 Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

PMID 7874169 1994 A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.

PMID 16957473 2006 We report a four-generation family with an FGFR1 P252R mutation, who have typical hand and feet skeletal features of Pfeiffer syndrome without craniofacial involvement.

PMID 14613973 2004 However, unlike the Apert syndrome Pro253Arg FGFR2c mutant, neither the Pfeiffer syndrome Pro250Arg FGFR1c mutant nor the Muenke syndrome Pro250Arg FGFR3c mutant bound appreciably to FGF7 or FGF10.

PMID 10942429 2000 These studies provide direct genetic evidence that the Pro252Arg mutation in FGFR1 causes human Pfeiffer syndrome and uncovers a molecular mechanism in which Fgf/Fgfr1 signals regulate intramembraneous bone formation by modulating Cbfa1 expression.

PMID 7795583 1995 Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.

PMID 14564217 2003 We report four new affected families showing an FGFR1 P252R mutation and emphasize the characteristic malformations of the feet in this form of Pfeiffer syndrome.

PMID 25251565 2014 Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation.

PMID 10861678 2000 Molecular analysis of her fibroblast growth factor receptor 1 gene (FGFR1) identified a heterozygous P252R missense mutation, previously only reported with FGFR1-Pfeiffer syndrome like manifestations.

PMID 12627230 2003 Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.

PMID 16764984 2006 Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.

PMID 28754744 2017 KLB, encoding β-Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism.

PMID 27502037 2016 Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

rs57709857 in FGFR1 gene and Schizophrenia PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs515726224 in FGFR1 gene and Sense of smell impaired PMID 24204987 2013 Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys.

rs1057519897 in FGFR1 gene and Transitional cell carcinoma of bladder PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs3213849 in FGFR1 gene and Waist-Hip Ratio PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.