Fibroblast growth factor 23

FGF23
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2P39
Identifiers
Aliases	FGF23, ADHR, FGFN, HPDR2, HYPF, PHPTC, fibroblast growth factor 23
External IDs	OMIM: 605380 MGI: 1891427 HomoloGene: 10771 GeneCards: FGF23
Gene ontology Molecular function • fibroblast growth factor receptor binding • type 1 fibroblast growth factor receptor binding • growth factor activity • receptor binding • protein tyrosine kinase activity • Ras guanyl-nucleotide exchange factor activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity • 1-phosphatidylinositol-3-kinase activity Cellular component • extracellular space • extracellular region • Golgi lumen Biological process • cell differentiation • negative regulation of bone mineralization • cellular response to interleukin-6 • vitamin D metabolic process • regulation of bone mineralization • phosphate ion homeostasis • cellular phosphate ion homeostasis • response to magnesium ion • regulation of phosphate transport • cellular response to vitamin D • negative regulation of osteoblast differentiation • cellular response to leptin stimulus • positive regulation of transcription, DNA-templated • fibroblast growth factor receptor signaling pathway • response to sodium phosphate • positive regulation of ERK1 and ERK2 cascade • positive regulation of vitamin D 24-hydroxylase activity • phosphate-containing compound metabolic process • vitamin D catabolic process • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway • cellular response to parathyroid hormone stimulus • negative regulation of hormone secretion • phosphatidylinositol-mediated signaling • positive regulation of GTPase activity • phosphatidylinositol phosphorylation • peptidyl-tyrosine phosphorylation • regulation of phosphatidylinositol 3-kinase signaling • phosphatidylinositol-3-phosphate biosynthetic process • MAPK cascade 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_065689.1	NP_073148.1
Location (UCSC)	Chr 12: 4.37 – 4.38 Mb	Chr 6: 127.07 – 127.08 Mb
PubMed search	[1]	[2]
Wikidata

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View/Edit Mouse

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene.^[3] FGF23 is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate and vitamin D metabolism.^[4][5]

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.^[6] 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.^[5]

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.^[7] 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.^[8] 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

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Yamashita T, Yoshioka M, Itoh N (October 2000). "Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain". Biochem. Biophys. Res. Commun. 277 (2): 494–8. doi:10.1006/bbrc.2000.3696. PMID 11032749.
4. Fukumoto S (2008). "Physiological regulation and disorders of phosphate metabolism--pivotal role of fibroblast growth factor 23". Intern. Med. 47 (5): 337–43. doi:10.2169/internalmedicine.47.0730. PMID 18310961.
5. Perwad F (2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro.". Am J Physiol Renal Physiol. 293: F1577–83. doi:10.1152/ajprenal.00463.2006. PMID 17699549.
6. Jüppner H (2011). "Phosphate and FGF-23". Kidney Int. Suppl. 79 (121): S24–7. doi:10.1038/ki.2011.27. PMC 3257051. PMID 21346724.
7. Zadik Y, Nitzan DW (October 2011). "Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?". Oral Oncol. 48 (2): e9–10. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764.
8. "Entrez Gene: FGF23 fibroblast growth factor 23".

Further reading

• Kiela PR, Ghishan FK (January 2009). "Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis". Lab. Invest. 89 (1): 7–14. doi:10.1038/labinvest.2008.114. PMID 19029978.
• Silve C, Beck L (2003). "Is FGF23 the long sought after phosphaturic factor phosphatonin?". Nephrol. Dial. Transplant. 17 (6): 958–61. doi:10.1093/ndt/17.6.958. PMID 12032180.
• Quarles LD (2003). "FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization". Am. J. Physiol. Endocrinol. Metab.. 285 (1): E1–9. doi:10.1152/ajpendo.00016.2003 (inactive 2015-01-13). PMID 12791601.
• Fukagawa M, Nii-Kono T, Kazama JJ (2005). "Role of fibroblast growth factor 23 in health and in chronic kidney disease". Curr. Opin. Nephrol. Hypertens. 14 (4): 325–9. doi:10.1097/01.mnh.0000172717.49476.80. PMID 15930999.
• Imel EA, Econs MJ (2006). "Fibroblast growth factor 23: roles in health and disease". J. Am. Soc. Nephrol. 16 (9): 2565–75. doi:10.1681/ASN.2005050573. PMID 16033853.
• Liu S, Quarles LD (2007). "How fibroblast growth factor 23 works". J. Am. Soc. Nephrol. 18 (6): 1637–47. doi:10.1681/ASN.2007010068. PMID 17494882.
• Econs MJ (2000). "Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23". Nat. Genet. 26 (3): 345–8. doi:10.1038/81664. PMID 11062477.
• White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, Lorenz-Depiereux B, Miyauchi A, Yang IM, Ljunggren O, Meitinger T, Strom TM, Jüppner H, Econs MJ (2001). "The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting". J. Clin. Endocrinol. Metab. 86 (2): 497–500. doi:10.1210/jc.86.2.497. PMID 11157998.
• Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2001). "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6500–5. Bibcode:2001PNAS...98.6500S. doi:10.1073/pnas.101545198. PMC 33497. PMID 11344269.
• Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC (2001). "FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate". Biochem. Biophys. Res. Commun. 284 (4): 977–81. doi:10.1006/bbrc.2001.5084. PMID 11409890.
• White KE, Carn G, Lorenz-Depiereux B, Benet-Pages A, Strom TM, Econs MJ (2002). "Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23". Kidney Int. 60 (6): 2079–86. doi:10.1046/j.1523-1755.2001.00064.x. PMID 11737582.
• Kruse K, Woelfel D, Strom TM, Storm TM (2002). "Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation". Horm. Res. 55 (6): 305–8. doi:10.1159/000050018. PMID 11805436.
• Yamashita T, Konishi M, Miyake A, Inui K, Itoh N (2002). "Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway". J. Biol. Chem. 277 (31): 28265–70. doi:10.1074/jbc.M202527200. PMID 12032146.
• Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N (2003). "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production". J. Biol. Chem. 278 (4): 2206–11. doi:10.1074/jbc.M207872200. PMID 12419819.
• Bai XY, Miao D, Goltzman D, Karaplis AC (2003). "The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency". J. Biol. Chem. 278 (11): 9843–9. doi:10.1074/jbc.M210490200. PMID 12519781.
• Larsson T, Zahradnik R, Lavigne J, Ljunggren O, Jüppner H, Jonsson KB (2003). "Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia". Eur. J. Endocrinol. 148 (2): 269–76. doi:10.1530/eje.0.1480269. PMID 12590648.
• Campos M, Couture C, Hirata IY, Juliano MA, Loisel TP, Crine P, Juliano L, Boileau G, Carmona AK (2003). "Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein". Biochem. J. 373 (Pt 1): 271–9. doi:10.1042/BJ20030287. PMC 1223479. PMID 12678920.

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