Fibroblast growth factor 23
Encyclopedia
Fibroblast growth factor 23 or FGF23 is a protein
that in humans is encoded by the FGF23 gene
. FGF23 is a member of the fibroblast growth factor
(FGF) family which is responsible for phosphate
metabolism.
, morphogenesis
, tissue repair, tumor growth and invasion. The product of this gene inhibits renal tubular phosphate transport. FGF23 is known as a phosphaturic hormone, in that it inhibits renal reabsorption of phosphate in the kidney, mostly in the proximal convoluted tubule. FGF23 is mostly expressed in bone and connective tissue and prior to 2000 was known in the scientific community as phosphatonin. The factor itself was hypothesized following case studies of hypophosphatemic diseases such as X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and (tumor induced) oncogenic osteomalacia. Also, FGF23 inhibits 1-hydroxylase. 1-hydroxylase is responsible for the conversion of calcifediol to calcitriol (the biologically active form of Vitamin D).
s. Mutations in FGF23 that render the protein resistant to proteolytic cleavage 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 tumor
s, such as the benign
mesenchymal neoplasm Phosphaturic mesenchymal tumor
causing tumor-induced osteomalacia, a paraneoplastic syndrome
. Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis
.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FGF23 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. FGF23 is a member of the fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
(FGF) family which is responsible for phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
metabolism.
Function
FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growthCell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
, tissue repair, tumor growth and invasion. The product of this gene inhibits renal tubular phosphate transport. FGF23 is known as a phosphaturic hormone, in that it inhibits renal reabsorption of phosphate in the kidney, mostly in the proximal convoluted tubule. FGF23 is mostly expressed in bone and connective tissue and prior to 2000 was known in the scientific community as phosphatonin. The factor itself was hypothesized following case studies of hypophosphatemic diseases such as X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and (tumor induced) oncogenic osteomalacia. Also, FGF23 inhibits 1-hydroxylase. 1-hydroxylase is responsible for the conversion of calcifediol to calcitriol (the biologically active form of Vitamin D).
Clinical signficance
FGF23 is located on chromosome 12 and is composed of three exonExon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s. Mutations in FGF23 that render the protein resistant to proteolytic cleavage leads to increased activity of FGF23 and the renal
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
phosphate loss found in the human disease autosomal dominant hypophosphatemic rickets
Autosomal dominant hypophosphatemic rickets
Autosomal dominant hypophosphatemic rickets is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones , bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblast growth factor 23...
. FGF23 is also overproduced by some types of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s, such as the benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
mesenchymal neoplasm Phosphaturic mesenchymal tumor
Phosphaturic mesenchymal tumor
Phosphaturic mesenchymal tumor is a benign neoplasm of mesenchymal origin, that produces phosphatonin . This tumor may cause tumor-induced osteomalacia, a paraneoplastic syndrome, by the secretion of phosphatonin, which has phosphaturic activity Phosphaturic mesenchymal tumor is a benign neoplasm...
causing tumor-induced osteomalacia, a paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
. Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis
Calcinosis
-Dystrophic calcification:The most common type of calcinosis is dystrophic calcification. This type of calcification can occur as a response to any soft tissue damage, including that involved in implantation of medical devices.-Metastatic calcification:...
.
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.