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Fibroblast growth factor 23

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(Redirected from FGF23 (gene))

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; OMA:FGF23 - orthologs
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: 127.05 – 127.06 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fibroblast growth factor 23 (FGF-23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the FGF23 gene. FGF-23 decreases reabsorption of phosphate in the kidney. Mutations in FGF23 can lead to its increased activity, resulting in autosomal dominant hypophosphatemic rickets.

Description

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Fibroblast growth factor 23 (FGF23) is a protein which 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]

Function

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FGF23´s main function is to regulate the phosphate concentration in plasma. It does this by decreasing reabsorption of phosphate in the kidney, which means phosphate is excreted in urine. FGF23 is secreted by osteocytes in response to increased calcitriol and phosphate.[8][9][10][11] FGF23 acts on the kidneys by decreasing the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule.[12]

FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.[7][13]

Genetics

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In humans FGF23 is encoded by the FGF23 gene, which is located on chromosome 12 and is composed of three exons. The gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets.[14]

Clinical significance

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Mutations in FGF23, which render the protein resistant to proteolytic cleavage, lead to its increased activity and to renal phosphate loss, in the human disease autosomal dominant hypophosphatemic rickets.

FGF23 can also be overproduced by some types of tumors, such as the benign mesenchymal neoplasm phosphaturic mesenchymal tumor causing tumor-induced osteomalacia, a paraneoplastic syndrome.[15][16]

Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis. Mice lacking either FGF23 or the klotho enzyme age prematurely due to hyperphosphatemia.[17]

Over-expression of FGF23 has been associated with cardiovascular disease in chronic kidney disease including cardiomyocyte hypertrophy, vascular calcification, stroke, and endothelial dysfunction.[18]

FGF23 expression and cleavage is promoted by iron deficiency and inflammation.[19]

FGF23 is associated with at least 7 non-nutritional diseases of hypophosphatemia: aside from autosomal dominant hypophosphatemic rickets, X-linked hypophosphatemia, autosomal recessive hypophosphatemic rickets type 1, 2, and 3, Tumor-induced osteomalacia and Hypophosphatemic rickets with hypercalciuria.[18]

History

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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.[20] 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

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  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): 494–498. 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): 337–343. 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–F1583. doi:10.1152/ajprenal.00463.2006. PMID 17699549. S2CID 20559055.
  8. ^ Dance A (23 February 2022). "Fun facts about bones: More than just scaffolding". Knowable Magazine. doi:10.1146/knowable-022222-1. S2CID 247095495. Retrieved 8 March 2022.
  9. ^ 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.
  10. ^ 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.
  11. ^ Brown RB, Razzaque MS (January 2018). "Chapter 31 - Endocrine Regulation of Phosphate Homeostasis". In Singh AK, Williams GH (eds.). Textbook of Nephro-Endocrinology (Second ed.). Academic Press. pp. 539–548. doi:10.1016/b978-0-12-803247-3.00032-5. hdl:10012/15679. ISBN 978-0-12-803247-3. S2CID 102827267.
  12. ^ 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.
  13. ^ Rodríguez-Ortiz ME, Rodríguez M (2015). "FGF23 as a calciotropic hormone". F1000Research. 4: 1472. doi:10.12688/f1000research.7189.1. PMC 4815615. PMID 27081473.
  14. ^ "Entrez Gene: FGF23 fibroblast growth factor 23".
  15. ^ 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.
  16. ^ 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.
  17. ^ Huang CL (May 2010). "Regulation of ion channels by secreted Klotho: mechanisms and implications". Kidney International. 77 (10): 855–860. doi:10.1038/ki.2010.73. PMID 20375979.
  18. ^ a b Beck-Nielsen SS, Mughal Z, Haffner D, Nilsson O, Levtchenko E, Ariceta G, et al. (February 2019). "FGF23 and its role in X-linked hypophosphatemia-related morbidity". Orphanet Journal of Rare Diseases. 14 (1): 58. doi:10.1186/s13023-019-1014-8. PMC 6390548. PMID 30808384.
  19. ^ David V, Martin A, Isakova T, Spaulding C, Qi L, Ramirez V, et al. (January 2016). "Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production". Kidney International. 89 (1): 135–146. doi:10.1038/ki.2015.290. PMC 4854810. PMID 26535997.
  20. ^ 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): 5945–5946. doi:10.1073/pnas.11154898. PMC 33399. PMID 11371627.

Further reading

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

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