Fibroblast growth factor 23

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FGF23
Protein FGF23 PDB 2p39.png
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)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for FGF23
Genomic location for FGF23
Band12p13.32Start4,368,227 bp[1]
End4,379,728 bp[1]
RNA expression pattern
PBB GE FGF23 221166 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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[edit]

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[edit]

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[edit]

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[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118972 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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[edit]

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