FGFR2

The FGFR2 gene encodes a protein called fibroblast growth factor receptor 2. The protein is involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development (R). 

Mutations can lead to a higher risk of cancer and other immune diseases (R). 

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.

     Apert syndrome 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 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. breast cancer Genetics Home Reference provides information about breast cancer. cholangiocarcinoma Genetics Home Reference provides information about cholangiocarcinoma. Crouzon syndrome 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. epidermal nevus Genetics Home Reference provides information about epidermal nevus. Jackson-Weiss syndrome 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 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 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. prostate cancer Genetics Home Reference provides information about prostate cancer. cancers 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, breast, cervical, pancreatic, and head and neck cancers.

     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.