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, HFTC2
External IDs	OMIM: 605380; MGI: 1891427; HomoloGene: 10771; GeneCards: FGF23; OMA:FGF23 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12p13.32 Start 4,368,227 bp End 4,379,712 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 F3 Start 127,049,865 bp End 127,058,371 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve gonad testicle right auricle liver right lobe of liver muscle of thigh muscle tissue primary visual cortex blood Top expressed in embryo lumbar spinal ganglion zygote lumbar subsegment of spinal cord tibiofemoral joint superior frontal gyrus extraocular muscle vastus lateralis muscle carotid body major salivary gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function fibroblast growth factor receptor binding type 1 fibroblast growth factor receptor binding growth factor activity protein tyrosine kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity 1-phosphatidylinositol-3-kinase activity protein binding Cellular component extracellular region Golgi lumen endoplasmic reticulum lumen extracellular space 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 phosphate biosynthetic process peptidyl-tyrosine phosphorylation phosphatidylinositol-3-phosphate biosynthetic process MAPK cascade post-translational protein modification regulation of signaling receptor activity positive regulation of protein kinase B signaling Sources:Amigo / QuickGO
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: 127.05 – 127.06 Mb PubMed search
Wikidata
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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 and vitamin D metabolism.

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. 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.

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.

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.

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.

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. PMC 4292907. 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. 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.