Fibroblast growth factor 23

FGF23
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFGF23, ADHR, FGFN, HPDR2, HYPF, PHPTC, fibroblast growth factor 23, HFTC2
External IDsOMIM: 605380 MGI: 1891427 HomoloGene: 10771 GeneCards: FGF23
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12p13.32Start4,368,227 bp[1]
End4,379,728 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 6: 127.07 – 127.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene.[5] FGF23 is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate and vitamin D metabolism.[6][7]

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.[8] 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.[7][9]

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.[10]

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.[11]

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.[12] 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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000118972 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000000182 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ 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.
  6. ↑ 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.
  7. 1 2 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 (5): F1577–83. doi:10.1152/ajprenal.00463.2006. PMID 17699549.
  8. ↑ Jüppner H (2011). "Phosphate and FGF-23". Kidney Int. Suppl. 79 (121): S24–7. doi:10.1038/ki.2011.27. PMC 3257051. PMID 21346724.
  9. ↑ Rodríguez-Ortiz ME, Rodríguez M (2015). "FGF23 as a calciotropic hormone". F1000Research. 4: 1472. doi:10.12688/f1000research.7189.1. PMC 4815615. PMID 27081473.
  10. ↑ 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.
  11. ↑ "Entrez Gene: FGF23 fibroblast growth factor 23".
  12. ↑ Strewler, GJ (22 May 2001). "FGF23, hypophosphatemia, and rickets: has phosphatonin been found?". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 5945–6. doi:10.1073/pnas.11154898. PMC 33399. PMID 11371627.

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.
  • 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.

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