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Genetics Home Reference: your guide to understanding genetic conditions
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FGFR1

Reviewed July 2013

What is the official name of the FGFR1 gene?

The official name of this gene is “fibroblast growth factor receptor 1.”

FGFR1 is the gene's official symbol. The FGFR1 gene is also known by other names, listed below.

What is the normal function of the FGFR1 gene?

The FGFR1 gene provides instructions for making a protein called fibroblast growth factor receptor 1. This protein is one of four fibroblast growth factor receptors, which are related proteins that are involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development.

The FGFR1 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning allows the FGFR1 protein to interact with other proteins called fibroblast growth factors outside the cell and to receive signals that help the cell respond to its environment. When a fibroblast growth factor attaches to the FGFR1 protein, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes, such as maturing to take on specialized functions. The FGFR1 protein is thought to play an important role in the development of the nervous system. This protein may also help regulate the growth of long bones, such as the large bones in the arms and legs.

Does the FGFR1 gene share characteristics with other genes?

The FGFR1 gene belongs to a family of genes called CD (CD molecules). It also belongs to a family of genes called immunoglobulin superfamily, I-set domain containing (immunoglobulin superfamily, I-set domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the FGFR1 gene related to health conditions?

8p11 myeloproliferative syndrome - caused by mutations in the FGFR1 gene

The FGFR1 gene is involved in a type of blood cancer called 8p11 myeloproliferative syndrome. This condition is characterized by an increased number of white blood cells (myeloproliferative disorder) and the development of lymphoma, a blood-related cancer that causes tumor formation in the lymph nodes. The myeloproliferative disorder usually develops into another form of blood cancer called acute myeloid leukemia. 8p11 myeloproliferative syndrome results from a rearrangement (translocation) of genetic material between chromosome 8 and another chromosome, which fuses part of the FGFR1 gene with part of another gene from the other chromosome. The most common partner gene is ZMYM2 on chromosome 13. These translocations are found only in cancer cells.

Regardless of the partner gene, the protein produced from the fused gene turns on FGFR1 signaling without the need for stimulation from growth factors. The uncontrolled signaling promotes continuous cell growth and division, leading to cancer.

Kallmann syndrome - caused by mutations in the FGFR1 gene

Researchers have identified more than 40 FGFR1 gene mutations that cause Kallmann syndrome type 2, which is a condition characterized by delayed or absent puberty and an impaired sense of smell. These mutations change single protein building blocks (amino acids) in the FGFR1 protein or result in the production of an abnormally small, nonfunctional version of the protein. Because these mutations prevent the FGFR1 protein from transmitting signals properly, they are described as "loss-of-function" mutations.

During brain development, the altered FGFR1 protein disrupts the formation and movement (migration) of nerve cells that process smells (olfactory neurons). These neurons must come together into a bundle called the olfactory bulb for a person to perceive odors. Problems with the migration of nerve cells into the olfactory bulb underlie the impaired sense of smell in people with Kallmann syndrome. FGFR1 gene mutations also disrupt the migration of nerve cells that produce gonadotropin-releasing hormone (GnRH) in the developing brain. GnRH controls the production of several other hormones that direct sexual development before birth and during puberty. An altered FGFR1 protein prevents the normal migration of GnRH-producing nerve cells in the brain, which interferes with sexual development and causes puberty to be delayed or absent.

It is unclear how FGFR1 gene mutations lead to other signs and symptoms of Kallmann syndrome, including an opening in the roof of the mouth (a cleft palate) and abnormal tooth development. Because the features of this condition vary among individuals, researchers suspect that other genetic and environmental factors may be involved.

osteoglophonic dysplasia - caused by mutations in the FGFR1 gene

Several mutations in the FGFR1 gene can cause a rare condition called osteoglophonic dysplasia. This condition is characterized by abnormal bone growth that leads to head and face (craniofacial) abnormalities and dwarfism. FGFR1 gene mutations that cause osteoglophonic dysplasia change single amino acids in the FGFR1 protein. The altered FGFR1 protein appears to cause prolonged signaling, which promotes premature fusion of bones in the skull and disrupts the regulation of bone growth in the arms and legs, leading to craniofacial abnormalities and shortened limbs. Because the FGFR1 gene mutations that cause osteoglophonic dysplasia abnormally enhance FGFR1 signaling, they are described as "gain-of-function" mutations.

Pfeiffer syndrome - caused by mutations in the FGFR1 gene

Another gain-of-function mutation in the FGFR1 gene causes type 1 Pfeiffer syndrome. This condition is characterized by premature fusion of certain bones in the skull (craniosynostosis), which leads to a misshapen head and distinctive facial features. Affected individuals also have hand and foot abnormalities. The FGFR1 gene mutation that causes this condition changes a single amino acid in the FGFR1 protein: the amino acid proline is replaced with the amino acid arginine at protein position 252 (written as Pro252Arg). The altered FGFR1 protein appears to cause prolonged signaling, which promotes early fusion of the skull bones and affects the development of bones in the hands and feet.

cancers - associated with the FGFR1 gene

Alterations in the activity (expression) of the FGFR1 gene are associated with certain cancers. The altered gene expression may enhance several cancer-related events such as cell division, cell movement, and the development of new blood vessels that nourish a growing tumor.

The FGFR1 gene is abnormally active (overexpressed) in certain types of stomach and prostate cancers. This amplification is associated with tumor progression and a poorer outcome. Altered FGFR1 gene expression has also been found in pancreatic, esophageal, ovarian, testicular, breast, and head and neck cancers.

Where is the FGFR1 gene located?

Cytogenetic Location: 8p11.23-p11.22

Molecular Location on chromosome 8: base pairs 38,411,137 to 38,468,833

The FGFR1 gene is located on the short (p) arm of chromosome 8 between positions 11.23 and 11.22.

The FGFR1 gene is located on the short (p) arm of chromosome 8 between positions 11.23 and 11.22.

More precisely, the FGFR1 gene is located from base pair 38,411,137 to base pair 38,468,833 on chromosome 8.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about FGFR1?

You and your healthcare professional may find the following resources about FGFR1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the FGFR1 gene or gene products?

  • BFGFR
  • CD331
  • CEK
  • C-FGR
  • FGFR1_HUMAN
  • fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)
  • FLG
  • FLJ14326
  • FLT2
  • FMS-like gene
  • FMS-like tyrosine kinase 2
  • heparin-binding growth factor receptor 1
  • hydroxyaryl-protein kinase
  • KAL2
  • N-SAM tyrosine kinase
  • protein-tyrosine kinase
  • tyrosyl protein kinase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FGFR1?

acids ; acute ; acute myeloid leukemia ; amino acid ; anosmia ; arginine ; cancer ; cell ; cell division ; cell membrane ; chromosome ; cleft palate ; craniofacial ; craniosynostosis ; dwarfism ; dysplasia ; embryonic ; fibroblast ; gene ; gene expression ; growth factor ; hormone ; kinase ; leukemia ; lymph ; lymphoma ; mutation ; myeloid ; nervous system ; olfactory bulb ; ovarian ; palate ; pancreatic ; progression ; proline ; prostate ; protein ; puberty ; rearrangement ; receptor ; stomach ; syndrome ; translocation ; tumor ; tyrosine ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chen L, Deng CX. Roles of FGF signaling in skeletal development and human genetic diseases. Front Biosci. 2005 May 1;10:1961-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15769677?dopt=Abstract)
  • Dodé C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, Kottler ML, Chabrolle C, Gancel A, François I, Devriendt K, Wolczynski S, Pugeat M, Pineiro-Garcia A, Murat A, Bouchard P, Young J, Delpech M, Hardelin JP. Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. Hum Mutat. 2007 Jan;28(1):97-8. (http://www.ncbi.nlm.nih.gov/pubmed/17154279?dopt=Abstract)
  • Dodé C, Levilliers J, Dupont JM, De Paepe A, Le Dû N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pêcheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. Epub 2003 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/12627230?dopt=Abstract)
  • Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D, Ellis IO, Reis-Filho JS. FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res. 2007;9(2):R23. (http://www.ncbi.nlm.nih.gov/pubmed/17397528?dopt=Abstract)
  • Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. Epub 2005 Feb 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15863030?dopt=Abstract)
  • Farrow EG, Davis SI, Mooney SD, Beighton P, Mascarenhas L, Gutierrez YR, Pitukcheewanont P, White KE. Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. Am J Med Genet A. 2006 Mar 1;140(5):537-9. (http://www.ncbi.nlm.nih.gov/pubmed/16470795?dopt=Abstract)
  • Gene Review: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1334)
  • Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010 Apr;41(4):461-76. doi: 10.1016/j.humpath.2009.11.003. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20226962?dopt=Abstract)
  • Kim SH, Hu Y, Cadman S, Bouloux P. Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome. J Neuroendocrinol. 2008 Feb;20(2):141-63. Epub 2007 Nov 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18034870?dopt=Abstract)
  • Macdonald D, Reiter A, Cross NC. The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1. Acta Haematol. 2002;107(2):101-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11919391?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2260)
  • Pitteloud N, Acierno JS Jr, Meysing A, Eliseenkova AV, Ma J, Ibrahimi OA, Metzger DL, Hayes FJ, Dwyer AA, Hughes VA, Yialamas M, Hall JE, Grant E, Mohammadi M, Crowley WF Jr. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6281-6. Epub 2006 Apr 10. (http://www.ncbi.nlm.nih.gov/pubmed/16606836?dopt=Abstract)
  • Shin EY, Lee BH, Yang JH, Shin KS, Lee GK, Yun HY, Song YJ, Park SC, Kim EG. Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer. J Cancer Res Clin Oncol. 2000 Sep;126(9):519-28. (http://www.ncbi.nlm.nih.gov/pubmed/11003564?dopt=Abstract)
  • Valve EM, Nevalainen MT, Nurmi MJ, Laato MK, Martikainen PM, Härkönen PL. Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer. Lab Invest. 2001 Jun;81(6):815-26. (http://www.ncbi.nlm.nih.gov/pubmed/11406643?dopt=Abstract)
  • White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ, McKeown C, Fitzpatrick D, Yu K, Ornitz DM, Econs MJ. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005 Feb;76(2):361-7. Epub 2004 Dec 28. (http://www.ncbi.nlm.nih.gov/pubmed/15625620?dopt=Abstract)
  • Wilkie AO. Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations. Cytokine Growth Factor Rev. 2005 Apr;16(2):187-203. Epub 2005 Apr 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15863034?dopt=Abstract)
  • Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet. 1998 Jan;18(1):84-7. (http://www.ncbi.nlm.nih.gov/pubmed/9425908?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2013
Published: December 22, 2014