Fibroblast growth factor 23

Fibroblast growth factor 23
PDB rendering based on 2p39.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2P39​
Identifiers
Symbols	FGF23 ; ADHR; FGFN; HPDR2; HYPF; PHPTC
External IDs	OMIM: 605380 MGI: 1891427 HomoloGene: 10771 GeneCards: FGF23 Gene
Gene ontology Molecular function • type 1 fibroblast growth factor receptor binding • growth factor activity Cellular component • extracellular region • extracellular space • intracellular Biological process • phosphate-containing compound metabolic process • epidermal growth factor receptor signaling pathway • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • regulation of phosphate transport • positive regulation of vitamin D 24-hydroxylase activity • cell differentiation • negative regulation of bone mineralization • cellular phosphate ion homeostasis • Fc-epsilon receptor signaling pathway • vitamin D catabolic process • innate immune response • negative regulation of osteoblast differentiation • positive regulation of transcription, DNA-templated • negative regulation of hormone secretion • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • phosphate ion homeostasis • positive regulation of ERK1 and ERK2 cascade • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8074	64654
Ensembl	ENSG00000118972	ENSMUSG00000000182
UniProt	Q9GZV9	Q9EPC2
RefSeq (mRNA)	NM_020638	NM_022657
RefSeq (protein)	NP_065689	NP_073148
Location (UCSC)	Chr 12: 4.37 – 4.38 Mb	Chr 6: 127.07 – 127.08 Mb
PubMed search

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene.^[1] FGF23 is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate and vitamin D metabolism.^[2][3]

Function

The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by osteocytes in response to elevated Calcitriol. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule.^[4] Thus, FGF23 decreases the reabsorption and increases excretion of phosphate. FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.^[3]

Clinical significance

FGF23 is located on chromosome 12 and is composed of three exons. 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 tumors, such as the benign mesenchymal neoplasm Phosphaturic mesenchymal tumor causing tumor-induced osteomalacia, a paraneoplastic syndrome.^[5] 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.^[6] 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.Two major types of effects • Direct Effects: • 1. Impairs sodium dependent phosphate transport in both intestinal and renal brush border membrane vesicles • 2. Inhibits production of calcitriol and stimulates breakdown of calcitriol • 3. Inhibits production/secretion of parathyroid

References

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery 2p39: Crystal structure of human FGF23