FGFR1 gene

The FGFR1 gene provides instructions for a receptor protein that regulates cell growth, development, and signaling, and is implicated in various developmental disorders and cancers.

Normal Function

The FGFR1 gene provides instructions for making a protein called fibroblast growth factor receptor 1 (FGFR1). This protein is one of four fibroblast growth factor receptors, which are a family of proteins that are involved in 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, allowing it to interact with fibroblast growth factors (FGFs) outside the cell. When an FGF attaches to the FGFR1 protein, it triggers a series of chemical reactions inside the cell that signal the cell to undergo changes or learn new functions. This signaling is essential for the development of the brain, craniofacial bones, bones in the hands and feet, and long bones in the arms and legs.

FGFR1 also plays a critical role in the formation, survival, and movement of neurons, particularly those that produce gonadotropin-releasing hormone (GnRH), which controls sexual development. It is also involved in the processing of smells by olfactory neurons.

Health Conditions Related to Genetic Changes

8p11 myeloproliferative syndrome

This condition is a blood cancer characterized by an increase in white blood cells and the development of lymphoma. It is caused by a rearrangement (translocation) of genetic material between chromosome 8 and another chromosome, fusing part of the FGFR1 gene with another gene. This fusion protein triggers uncontrolled signaling, promoting continuous cell growth and division.

Encephalocraniocutaneous lipomatosis

Rare, non-inherited "gain-of-function" variants in the FGFR1 gene cause this condition, which is characterized by noncancerous tumors and abnormalities in the brain, eyes, and skin. These variants arise randomly in early development, resulting in mosaicism, where only some cells carry the mutation.

Hartsfield syndrome

Variants in the FGFR1 gene that reduce or eliminate protein function lead to Hartsfield syndrome. This condition is characterized by holoprosencephaly (a brain development abnormality) and split hand/foot malformations.

Kallmann syndrome

Loss-of-function variants in FGFR1 account for about 10 percent of Kallmann syndrome cases. This disorder involves hypogonadotropic hypogonadism (impaired sexual development) and an impaired sense of smell. The lack of functional FGFR1 disrupts the migration of olfactory and GnRH-producing neurons during brain development.

Osteoglophonic dysplasia

Gain-of-function variants in FGFR1 cause this rare condition, leading to abnormal bone growth, craniofacial abnormalities, craniosynostosis, and short stature. The overactive protein also increases the secretion of FGF23, which impairs bone health by affecting phosphate levels.

Pfeiffer syndrome

Gain-of-function variants in FGFR1 cause Pfeiffer syndrome, characterized by craniosynostosis (leading to a misshapen head) and hand and foot abnormalities due to prolonged signaling.

Other disorders

• Normosmic isolated hypogonadotropic hypogonadism (nIHH): Caused by variants that reduce FGFR1 function but do not affect the sense of smell.
• Other cancers: Somatic genetic changes, including gene amplification and amino acid changes, are associated with various cancers, including lung, breast, and brain tumors.
• Tumor-induced osteomalacia: Rearrangements involving FGFR1 can lead to the formation of phosphaturic mesenchymal tumors, causing bone softening and pain.

Other Names for This Gene

• BFGFR
• C-FGR
• CD331
• CEK
• 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