Fibroblast growth factor 23 (FGF23) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

and member of the

fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in the ...

(FGF) family which participates in the regulation of

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

in plasma and

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

metabolism. In humans it is encoded by the

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. FGF23 decreases reabsorption of phosphate in the kidney. Mutations in ''FGF23'' can lead to its increased activity, resulting in

autosomal dominant hypophosphatemic rickets Autosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones (rickets), bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblas ...

Description

Fibroblast growth factor 23 (FGF23) is a

which in humans is encoded by the

. FGF23 is a member of the

(FGF) family which participates in

and

metabolism and regulation.

Function

FGF23´s main function is to regulate the phosphate concentration in plasma. It does this by decreasing reabsorption of phosphate in the kidney, which means phosphate is excreted in urine. FGF23 is secreted by

osteocyte An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and ...

s in response to increased

calcitriol Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...

. FGF23 acts on the kidneys by decreasing the expression of NPT2, a sodium-phosphate cotransporter in the

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...

. FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate

and subsequently impairing calcium absorption.

Genetics

In humans FGF23 is encoded by the

, which is located on

chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...

and is composed of three

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s. The gene was identified by its mutations associated with

Clinical significance

Mutations in ''FGF23'', which render the protein resistant to proteolytic cleavage, lead to its increased activity and to

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

phosphate loss, in the human disease

. FGF23 can also be overproduced by some types of

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s, such as the

benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...

mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

neoplasm phosphaturic mesenchymal tumor causing

tumor-induced osteomalacia Oncogenic osteomalacia, also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor. Signs ...

, a

paraneoplastic syndrome A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...

. Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor

calcinosis Calcinosis is the formation of calcium deposits in any soft tissue. It is a rare condition that has many different causes. These range from infection and injury to systemic diseases like kidney failure. Types Dystrophic calcification The most c ...

. Mice lacking either FGF23 or the klotho enzyme age prematurely due to

hyperphosphatemia Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. Often there is also low calcium levels which can r ...

. Over-expression of FGF23 has been associated with cardiovascular disease in chronic kidney disease including cardiomyocyte hypertrophy, vascular calcification, stroke, and endothelial dysfunction. FGF23 expression and cleavage is promoted by

iron deficiency Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key ...

and inflammation. FGF23 is associated with at least 7 non-nutritional diseases of hypophosphatemia: aside from autosomal dominant hypophosphatemic rickets,

X-linked hypophosphatemia X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short st ...

, autosomal recessive hypophosphatemic rickets type 1, 2, and 3,

Tumor-induced osteomalacia Oncogenic osteomalacia, also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor. Signs ...

and Hypophosphatemic rickets with hypercalciuria.

History

Prior to its discovery in 2000, it was hypothesized that a protein existed which performed the functions subsequently shown for FGF23. This putative protein was known as phosphatonin. Several types of effects were described including impairment of sodium dependent phosphate transport in both intestinal and renal brush border membrane vesicles, inhibition of production of calcitriol, stimulation of breakdown of calcitriol, and inhibition of production/secretion of parathyroid hormone.

Description

Function

Genetics

Clinical significance

History

References

Further reading