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Genetics Home Reference: your guide to understanding genetic conditions
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FGFR1

Reviewed August 2008

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 several 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 specific growth factors outside the cell and to receive signals that help the cell respond to its environment. When growth factors attach 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).

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?

Kallmann syndrome - caused by mutations in the FGFR1 gene

Researchers have identified more than 40 FGFR1 gene mutations that cause Kallmann syndrome type 2. 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.

Pfeiffer syndrome - caused by mutations in the FGFR1 gene

Type 1 Pfeiffer syndrome is caused by a mutation in the FGFR1 gene that changes a single amino acid in the FGFR1 protein. As a result of this mutation, 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 premature fusion of the skull bones and affects the development of bones in the hands and feet. Because the Pro252Arg mutation abnormally enhances FGFR1 signaling, it is described as a "gain of function" mutation.

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 (proliferation), cell movement, and the development of new blood vessels (angiogenesis) 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.

The FGFR1 gene is also involved in a type of blood cancer called 8p11 myeloproliferative syndrome. This type of cancer can result from a rearrangement (translocation) of genetic material between chromosome 8 and another chromosome. This translocation occurs only in cancer cells. It fuses part of the FGFR1 gene on chromosome 8 with part of another gene from the other chromosome. The protein produced from the fused gene overactivates FGFR1 signaling, which promotes the uncontrolled growth and division of cancer cells.

other disorders - caused by mutations in the FGFR1 gene

Several gain-of-function mutations in the FGFR1 gene can cause a rare condition called osteoglophonic dysplasia. This condition is characterized by the premature fusion of certain bones in the skull (craniosynostosis) and shortened limbs due to abnormal bone growth in the arms and legs. Craniosynostosis affects the shape of the head and face; among other features, people with this disorder have a prominent forehead and a short nose. FGFR1 gene mutations that cause osteoglophonic dysplasia change a single building block (amino acid) 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.

Where is the FGFR1 gene located?

Cytogenetic Location: 8p12

Molecular Location on chromosome 8: base pairs 38,268,655 to 38,326,351

The FGFR1 gene is located on the short (p) arm of chromosome 8 at position 12.

The FGFR1 gene is located on the short (p) arm of chromosome 8 at position 12.

More precisely, the FGFR1 gene is located from base pair 38,268,655 to base pair 38,326,351 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.

  • Educational resources - Information pages

    • American Cancer Society: What Are Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Diseases? (http://www.cancer.org/cancer/myelodysplasticsyndrome/detailedguide/index)
    • Eurekah Bioscience Collection: Fibroblast Growth Factors (FGFs) and FGF Receptors (http://www.ncbi.nlm.nih.gov/books/NBK6330/)
    • Human Molecular Genetics (second edition, 1999): FGFR Mutations (figure) (http://www.ncbi.nlm.nih.gov/books/NBK7574/?rendertype=figure&id=A2128)

  • Gene Reviews - Clinical summary

    • Gene Review: FGFR-Related Craniosynostosis (http://www.ncbi.nlm.nih.gov/books/NBK1455/)
    • Gene Review: Kallmann syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1334/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for FGFR1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2260%5Bgeneid%5D)

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

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((FGFR1%5BTIAB%5D)%20OR%20(fibroblast%20growth%20factor%20receptor%201%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201080%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • FIBROBLAST GROWTH FACTOR RECEPTOR 1 (http://omim.org/entry/136350)
    • HYPOGONADOTROPIC HYPOGONADISM 7 WITH OR WITHOUT ANOSMIA (http://omim.org/entry/146110)
    • OSTEOGLOPHONIC DYSPLASIA (http://omim.org/entry/166250)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_FGFR1.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/2260)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=2260)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=3688)

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 ; amino acid ; angiogenesis ; anosmia ; cancer ; cell ; cell division ; cell membrane ; chromosome ; cleft palate ; craniosynostosis ; dysplasia ; embryonic ; fibroblast ; gene ; gene expression ; growth factor ; hormone ; kinase ; mutation ; nervous system ; olfactory bulb ; ovarian ; palate ; pancreatic ; progression ; proliferation ; prostate ; protein ; puberty ; rearrangement ; receptor ; stomach ; syndrome ; translocation ; tumor ; tyrosine

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)
  • DiMario JX. Activation and repression of growth factor receptor gene transcription (Review). Int J Mol Med. 2002 Jul;10(1):65-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12060852?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)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/2260)
  • 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: Kallmann syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1334/)
  • Groth C, Lardelli M. The structure and function of vertebrate fibroblast growth factor receptor 1. Int J Dev Biol. 2002;46(4):393-400. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12141425?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)
  • 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)
  • Pitteloud N, Quinton R, Pearce S, Raivio T, Acierno J, Dwyer A, Plummer L, Hughes V, Seminara S, Cheng YZ, Li WP, Maccoll G, Eliseenkova AV, Olsen SK, Ibrahimi OA, Hayes FJ, Boepple P, Hall JE, Bouloux P, Mohammadi M, Crowley W. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest. 2007 Feb;117(2):457-63. Epub 2007 Jan 18. (http://www.ncbi.nlm.nih.gov/pubmed/17235395?dopt=Abstract)
  • Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T. 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. J Clin Endocrinol Metab. 2004 Mar;89(3):1079-88. (http://www.ncbi.nlm.nih.gov/pubmed/15001591?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)
  • Trarbach EB, Costa EM, Versiani B, de Castro M, Baptista MT, Garmes HM, de Mendonca BB, Latronico AC. Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab. 2006 Oct;91(10):4006-12. Epub 2006 Aug 1. Erratum in: J Clin Endocrinol Metab. 2008 May;93(5):2013. (http://www.ncbi.nlm.nih.gov/pubmed/16882753?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)

 

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: August 2008
Published: June 17, 2013