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FGFR2

Reviewed June 2013

What is the official name of the FGFR2 gene?

The official name of this gene is “fibroblast growth factor receptor 2.”

FGFR2 is the gene's official symbol. The FGFR2 gene is also known by other names, listed below.

What is the normal function of the FGFR2 gene?

The FGFR2 gene provides instructions for making a protein called fibroblast growth factor receptor 2. 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 FGFR2 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 FGFR2 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 FGFR2 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 FGFR2 protein plays an important role in bone growth, particularly during embryonic development. For example, this protein signals certain immature cells in the developing embryo to become bone cells in the head, hands, feet, and other tissues.

There are several slightly different versions (isoforms) of the FGFR2 protein. Specific patterns of these isoforms are found in the body's tissues, and these patterns may change throughout growth and development.

Does the FGFR2 gene share characteristics with other genes?

The FGFR2 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 FGFR2 gene related to health conditions?

Apert syndrome - caused by mutations in the FGFR2 gene

At least seven mutations in the FGFR2 gene have been found to cause Apert syndrome, a condition that causes premature closure of the bones of the skull (craniosynostosis), leading to a misshapen head and distinctive facial features, and abnormalities of the fingers and toes. Nearly all cases of Apert syndrome are caused by one of two mutations in the FGFR2 gene. These mutations change single protein building blocks (amino acids) in the FGFR2 protein, which alters the protein's 3-dimensional structure. One mutation replaces the amino acid serine with the amino acid tryptophan at protein position 252 (written as Ser252Trp). The other mutation replaces the amino acid proline with the amino acid arginine at position 253 (written as Pro253Arg). The altered FGFR2 protein appears to cause stronger signaling, which promotes the premature fusion of bones in the skull, hands, and feet.

Beare-Stevenson cutis gyrata syndrome - caused by mutations in the FGFR2 gene

At least three mutations in the FGFR2 gene have been found to cause Beare-Stevenson cutis gyrata syndrome, a condition that causes craniosynostosis, leading to a misshapen head and distinctive facial features, and a skin abnormality called cutis gyrata. The most common mutation replaces the amino acid tyrosine with the amino acid cysteine at position 375 in the protein (written as Tyr375Cys). The FGFR2 gene mutations that cause Beare-Stevenson cutis gyrata syndrome appear to overactivate signaling by the FGFR2 protein, which promotes the premature fusion of bones in the skull.

Crouzon syndrome - caused by mutations in the FGFR2 gene

At least 40 mutations in the FGFR2 gene can cause Crouzon syndrome, a condition that causes craniosynostosis, leading to a misshapen head and distinctive facial features. Most of the mutations that cause Crouzon syndrome change single DNA building blocks (nucleotides) in the FGFR2 gene. Insertions and deletions of a small number of nucleotides are also known to cause the disorder. These mutations in FGFR2 appear to overactivate signaling by the FGFR2 protein, which promotes premature fusion of bones in the skull.

Jackson-Weiss syndrome - caused by mutations in the FGFR2 gene

At least six mutations in the FGFR2 gene have been found to cause Jackson-Weiss syndrome. This condition causes craniosynostosis, leading to a misshapen head and distinctive facial features, and foot abnormalities. Each of the mutations changes a single amino acid in a region of the FGFR2 protein known as the IgIII domain, which is critical for receiving signals and interacting with growth factors. The mutations appear to overactivate signaling by the FGFR2 protein, which promotes premature fusion of skull bones and affects the development of bones in the feet.

lacrimo-auriculo-dento-digital syndrome - caused by mutations in the FGFR2 gene

At least two mutations in the FGFR2 gene have been found to cause lacrimo-auriculo-dento-digital (LADD) syndrome. These mutations reduce the FGFR2 receptor protein's ability to trigger chemical reactions within cells when it binds to its growth factor. A mutation that occurs in some people with LADD syndrome replaces the amino acid alanine with the amino acid threonine at position 628 in the FGFR2 receptor protein (written as Ala628Thr or A628T).

The main features of LADD syndrome are abnormal tear production, malformed ears with hearing loss, decreased saliva production, small teeth, and hand deformities. The FGFR2 gene mutations that cause LADD syndrome reduce the function of the receptor protein, resulting in a decrease in cell signaling. These defects in cell signaling disrupt cell maturation and development, which results in abnormal formation of glands in the eyes and mouth, the ears, and the skeleton in people with LADD syndrome.

Pfeiffer syndrome - caused by mutations in the FGFR2 gene

More than 25 mutations in the FGFR2 gene can cause Pfeiffer syndrome, a condition that causes craniosynostosis, leading to a misshapen head and distinctive facial features, and hand and foot abnormalities. Several of the mutations that cause this condition change the number of cysteine amino acids in a critical region of the FGFR2 protein known as the IgIII domain. The remaining mutations affect amino acids other than cysteine or result in an FGFR2 protein that is missing one or more amino acids. These mutations appear to overactivate signaling by the FGFR2 protein, which promotes premature fusion of skull bones and affects the development of bones in the hands and feet.

cancers - associated with the FGFR2 gene

Alterations in the activity (expression) of the FGFR2 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 that nourish a growing tumor.

The FGFR2 gene is abnormally active (overexpressed) in certain types of stomach cancers, and this amplification is associated with a poor disease outcome. Abnormal expression of the FGFR2 gene is also found in patients with prostate cancer. A shift in the expression of two specific FGFR2 isoforms, IIIb and IIIc, appears to correlate with prostate cancer progression. This change in expression is complex, however, and varies depending on the type of prostate tumor. More advanced tumors may show an increase in the IIIb isoform, while other prostate tumors show a decrease in IIIb but an increase in IIIc. Altered FGFR2 gene expression is also associated with ovarian, cervical, pancreatic, and head and neck cancers.

Where is the FGFR2 gene located?

Cytogenetic Location: 10q26

Molecular Location on chromosome 10: base pairs 121,478,329 to 121,598,457

The FGFR2 gene is located on the long (q) arm of chromosome 10 at position 26.

The FGFR2 gene is located on the long (q) arm of chromosome 10 at position 26.

More precisely, the FGFR2 gene is located from base pair 121,478,329 to base pair 121,598,457 on chromosome 10.

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 FGFR2?

You and your healthcare professional may find the following resources about FGFR2 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 FGFR2 gene or gene products?

  • bacteria-expressed kinase
  • BEK
  • BEK fibroblast growth factor receptor
  • BEK protein tyrosine kinase
  • BFR-1
  • CD332
  • CEK3
  • CFD1
  • ECT1
  • FGFR2_HUMAN
  • FGF receptor
  • keratinocyte growth factor receptor
  • KGFR
  • K-SAM
  • protein tyrosine kinase, receptor like 14
  • TK14
  • TK25
  • tyrosylprotein 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 FGFR2?

acids ; alanine ; amino acid ; arginine ; bacteria ; cancer ; cell ; cell division ; cell membrane ; craniosynostosis ; critical region ; cysteine ; DNA ; domain ; embryo ; embryonic ; expressed ; fibroblast ; gene ; gene expression ; growth factor ; isoforms ; keratinocyte ; kinase ; mutation ; ovarian ; pancreatic ; progression ; proliferation ; proline ; prostate ; protein ; receptor ; serine ; stomach ; syndrome ; threonine ; tryptophan ; 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

  • Carinci F, Pezzetti F, Locci P, Becchetti E, Carls F, Avantaggiato A, Becchetti A, Carinci P, Baroni T, Bodo M. Apert and Crouzon syndromes: clinical findings, genes and extracellular matrix. J Craniofac Surg. 2005 May;16(3):361-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15915098?dopt=Abstract)
  • 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)
  • Cornejo-Roldan LR, Roessler E, Muenke M. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. Hum Genet. 1999 May;104(5):425-31. (http://www.ncbi.nlm.nih.gov/pubmed/10394936?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)
  • Ibrahimi OA, Chiu ES, McCarthy JG, Mohammadi M. Understanding the molecular basis of Apert syndrome. Plast Reconstr Surg. 2005 Jan;115(1):264-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15622262?dopt=Abstract)
  • Ibrahimi OA, Zhang F, Eliseenkova AV, Linhardt RJ, Mohammadi M. Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity. Hum Mol Genet. 2004 Jan 1;13(1):69-78. Epub 2003 Nov 12. (http://www.ncbi.nlm.nih.gov/pubmed/14613973?dopt=Abstract)
  • Lajeunie E, Heuertz S, El Ghouzzi V, Martinovic J, Renier D, Le Merrer M, Bonaventure J. Mutation screening in patients with syndromic craniosynostoses indicates that a limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer syndrome. Eur J Hum Genet. 2006 Mar;14(3):289-98. (http://www.ncbi.nlm.nih.gov/pubmed/16418739?dopt=Abstract)
  • Lew ED, Bae JH, Rohmann E, Wollnik B, Schlessinger J. Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19802-7. Epub 2007 Dec 3. (http://www.ncbi.nlm.nih.gov/pubmed/18056630?dopt=Abstract)
  • Naimi B, Latil A, Fournier G, Mangin P, Cussenot O, Berthon P. Down-regulation of (IIIb) and (IIIc) isoforms of fibroblast growth factor receptor 2 (FGFR2) is associated with malignant progression in human prostate. Prostate. 2002 Aug 1;52(3):245-52. (http://www.ncbi.nlm.nih.gov/pubmed/12111699?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2263)
  • Rohmann E, Brunner HG, Kayserili H, Uyguner O, Nürnberg G, Lew ED, Dobbie A, Eswarakumar VP, Uzumcu A, Ulubil-Emeroglu M, Leroy JG, Li Y, Becker C, Lehnerdt K, Cremers CW, Yüksel-Apak M, Nürnberg P, Kubisch C, Schlessinger J, van Bokhoven H, Wollnik B. Mutations in different components of FGF signaling in LADD syndrome. Nat Genet. 2006 Apr;38(4):414-7. Epub 2006 Feb 26. Erratum in: Nat Genet. 2006 Apr;38(4):495. Kubisch, Chriütian [corrected to Kubisch, Christian]. (http://www.ncbi.nlm.nih.gov/pubmed/16501574?dopt=Abstract)
  • Shams I, Rohmann E, Eswarakumar VP, Lew ED, Yuzawa S, Wollnik B, Schlessinger J, Lax I. Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway. Mol Cell Biol. 2007 Oct;27(19):6903-12. Epub 2007 Aug 6. (http://www.ncbi.nlm.nih.gov/pubmed/17682060?dopt=Abstract)
  • Shams I, Rohmann E, Eswarakumar VP, Lew ED, Yuzawa S, Wollnik B, Schlessinger J, Lax I. Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway. Mol Cell Biol. 2007 Oct;27(19):6903-12. Epub 2007 Aug 6. (http://www.ncbi.nlm.nih.gov/pubmed/17682060?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)
  • Wilkie AO, Patey SJ, Kan SH, van den Ouweland AM, Hamel BC. FGFs, their receptors, and human limb malformations: clinical and molecular correlations. Am J Med Genet. 2002 Oct 15;112(3):266-78. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12357470?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: June 2013
Published: November 24, 2014