Fibroblast growth factor 23

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Protein FGF23 PDB 2p39.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesFGF23, ADHR, FGFN, HPDR2, HYPF, PHPTC, fibroblast growth factor 23, HFTC2
External IDsOMIM: 605380 MGI: 1891427 HomoloGene: 10771 GeneCards: FGF23
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 12: 4.37 – 4.38 MbChr 6: 127.05 – 127.06 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Fibroblast growth factor 23 (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 participates in phosphate and vitamin D metabolism and regulation.[6][7]


The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by osteocytes in response to increased 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 of calcium and increases excretion of phosphate.[9][10][11]

FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.[7][12]

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.[13][14]

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.[15] Mice lacking either FGF23 or the klotho enzyme display premature aging due to hyperphosphatemia.[16]


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.[17] 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.


  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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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". Biochemical and Biophysical Research Communications. 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". Internal Medicine. 47 (5): 337–43. doi:10.2169/internalmedicine.47.0730. PMID 18310961.
  7. ^ a b Perwad F, Zhang MY, Tenenhouse HS, Portale AA (November 2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro". American Journal of Physiology. Renal Physiology. 293 (5): F1577-83. doi:10.1152/ajprenal.00463.2006. PMID 17699549.
  8. ^ Jüppner H (April 2011). "Phosphate and FGF-23". Kidney International. Supplement. 79 (121): S24–S27. doi:10.1038/ki.2011.27. PMC 3257051. PMID 21346724.
  9. ^ Dance A (23 February 2022). "Fun facts about bones: More than just scaffolding". Knowable Magazine. doi:10.1146/knowable-022222-1. Retrieved 8 March 2022.
  10. ^ Robling AG, Bonewald LF (February 2020). "The Osteocyte: New Insights". Annual Review of Physiology. 82 (1): 485–506. doi:10.1146/annurev-physiol-021119-034332. PMC 8274561. PMID 32040934.
  11. ^ Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL (July 2008). "Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1". Proceedings of the National Academy of Sciences of the United States of America. 105 (28): 9805–9810. Bibcode:2008PNAS..105.9805C. doi:10.1073/pnas.0803223105. PMC 2474477. PMID 18606998.
  12. ^ Rodríguez-Ortiz ME, Rodríguez M (2015). "FGF23 as a calciotropic hormone". F1000Research. 4: 1472. doi:10.12688/f1000research.7189.1. PMC 4815615. PMID 27081473.
  13. ^ Zadik Y, Nitzan DW (February 2012). "Tumor induced osteomalacia: a forgotten paraneoplastic syndrome?". Oral Oncology. 48 (2): e9–10. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764.
  14. ^ Green D, Mohorianu I, Piec I, Turner J, Beadsmoore C, Toms A, et al. (December 2017). "MicroRNA expression in a phosphaturic mesenchymal tumour". Bone Reports. 7: 63–69. doi:10.1016/j.bonr.2017.09.001. PMC 5596358. PMID 28932769.
  15. ^ "Entrez Gene: FGF23 fibroblast growth factor 23".
  16. ^ Huang CL (May 2010). "Regulation of ion channels by secreted Klotho: mechanisms and implications". Kidney International. 77 (10): 855–60. doi:10.1038/ki.2010.73. PMID 20375979.
  17. ^ Strewler GJ (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.