Fibroblast growth factor 23

Fibroblast growth factor 23 or FGF23 is gene which is a member of the fibroblast growth factor (FGF) family and encodes a protein which is responsible for phosphate metabolism.

FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The product of this gene inhibits renal tubular phosphate transport.

FGF23 is located on chromosome 12 and is composed of three exons. Mutations in FGF23 which cause failure of proper gene splicing leads to increased activity of FGF23 and the renal phosphate loss found in the human disease autosomal dominant hypophosphatemic rickets. FGF23 is also overproduced by some types of tumors, causing tumor-produced osteomalacia. Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis.

There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving fibroblastic growth factor 23 (FGF23), the X-linked phosphate regulating endopeptidase homolog (PHEX), and a matrix extracellular phosphoglycoprotein (MEPE) that regulates systemic phosphate homeostasis and mineralization. Short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum. The short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurs without any changes in circulating levels of parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, or fibroblast growth factor 23 (FGF23). MEPE may be involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.

This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets. Prior to discovery in 2000, it was hypothesized that a protein existed which performed the function of FGF23. This putative protein was known as phosphatonin.