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Genetics Home Reference: your guide to understanding genetic conditions
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FGF23

Reviewed August 2012

What is the official name of the FGF23 gene?

The official name of this gene is “fibroblast growth factor 23.”

FGF23 is the gene's official symbol. The FGF23 gene is also known by other names, listed below.

What is the normal function of the FGF23 gene?

The FGF23 gene provides instructions for making a protein called fibroblast growth factor 23, which is produced in bone cells. This protein is necessary in regulating the phosphate levels within the body (phosphate homeostasis). Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally rid the body of excess phosphate by excreting it in urine, and they reabsorb this mineral into the bloodstream when more is needed. Fibroblast growth factor 23 signals the kidneys to stop reabsorbing phosphate into the bloodstream.

In order to function, fibroblast growth factor 23 must be released (secreted) from the cell and it must attach (bind) to a receptor protein. To be secreted from the cell, sugar molecules are attached to fibroblast growth factor 23 by another protein called ppGalNacT3 in a process called glycosylation. Glycosylation allows fibroblast growth factor 23 to move out of the cell and protects the protein from being broken down. Once outside the bone cell, the protein must bind to a receptor protein called FGF receptor 1 that spans the membrane of kidney cells. Binding of fibroblast growth factor 23 to its receptor stimulates signaling that stops phosphate reabsorption into the bloodstream.

Studies suggest that fibroblast growth factor 23 has additional functions. It helps determine how much phosphate from the diet is absorbed by the intestines and plays a role in regulating vitamin D.

Fibroblast growth factor 23 is normally cut (cleaved) at a certain site, which turns off (inactivates) the protein. The cleavage site is located at positions 179 to 180 in the string of building blocks (amino acids) that make up the protein. This cleavage helps regulate the amount of active fibroblast growth factor 23 circulating in the bloodstream.

How are changes in the FGF23 gene related to health conditions?

hereditary hypophosphatemic rickets - caused by mutations in the FGF23 gene

At least three mutations in the FGF23 gene have been found to cause a rare form of hereditary hypophosphatemic rickets known as autosomal dominant hypophosphatemic rickets. These mutations change single protein building blocks (amino acids) in fibroblast growth factor 23, which prevents the protein from being cleaved. As a result, the protein is not inactivated, and an increased amount of the full-length, active protein circulates in the bloodstream. Overactivity of fibroblast growth factor 23 reduces phosphate reabsorption by the kidneys, leading to low levels of phosphate in the blood (hypophosphatemia) and related problems with bone growth in people with autosomal dominant hypophosphatemic rickets.

hyperphosphatemic familial tumoral calcinosis - caused by mutations in the FGF23 gene

At least seven mutations in the FGF23 gene have been found to cause hyperphosphatemic familial tumoral calcinosis (HFTC), a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. Mutations in the FGF23 gene lead to the production of a protein with decreased function. This nonfunctional protein is quickly broken down in cells, leading to a shortage of available fibroblast growth factor 23. This protein shortage decreases signaling and increases the amount of phosphate that is reabsorbed back into the bloodstream by the kidneys, leading to hyperphosphatemia. Calcinosis results when the excess phosphate combines with calcium to form deposits that build up in soft tissues.

Where is the FGF23 gene located?

Cytogenetic Location: 12p13.3

Molecular Location on chromosome 12: base pairs 4,368,226 to 4,379,727

The FGF23 gene is located on the short (p) arm of chromosome 12 at position 13.3.

The FGF23 gene is located on the short (p) arm of chromosome 12 at position 13.3.

More precisely, the FGF23 gene is located from base pair 4,368,226 to base pair 4,379,727 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about FGF23?

You and your healthcare professional may find the following resources about FGF23 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the FGF23 gene or gene products?

  • ADHR
  • FGF-23
  • FGF23_HUMAN
  • HPDR2
  • HYPF
  • phosphatonin
  • PHPTC
  • tumor-derived hypophosphatemia-inducing factor

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FGF23?

acids ; autosomal ; autosomal dominant ; calcinosis ; calcium ; cell ; familial ; fibroblast ; gene ; glycosylation ; growth factor ; hereditary ; homeostasis ; kidney ; mineral ; phosphate ; protein ; proximal ; receptor ; renal ; rickets ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. (http://www.ncbi.nlm.nih.gov/pubmed/11062477?dopt=Abstract)
  • Bergwitz C, Jüppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med. 2010;61:91-104. doi: 10.1146/annurev.med.051308.111339. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20059333?dopt=Abstract)
  • Farrow EG, Imel EA, White KE. Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and αKlotho). Best Pract Res Clin Rheumatol. 2011 Oct;25(5):735-47. doi: 10.1016/j.berh.2011.10.020. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22142751?dopt=Abstract)
  • Fukumoto S. Physiological regulation and disorders of phosphate metabolism--pivotal role of fibroblast growth factor 23. Intern Med. 2008;47(5):337-43. Epub 2008 Mar 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18310961?dopt=Abstract)
  • Garringer HJ, Malekpour M, Esteghamat F, Mortazavi SM, Davis SI, Farrow EG, Yu X, Arking DE, Dietz HC, White KE. Molecular genetic and biochemical analyses of FGF23 mutations in familial tumoral calcinosis. Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E929-37. doi: 10.1152/ajpendo.90456.2008. Epub 2008 Aug 5. (http://www.ncbi.nlm.nih.gov/pubmed/18682534?dopt=Abstract)
  • Imel EA, Econs MJ. Fibroblast growth factor 23: roles in health and disease. J Am Soc Nephrol. 2005 Sep;16(9):2565-75. Epub 2005 Jul 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16033853?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8074)
  • Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E1-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12791601?dopt=Abstract)
  • Ramon I, Kleynen P, Body JJ, Karmali R. Fibroblast growth factor 23 and its role in phosphate homeostasis. Eur J Endocrinol. 2010 Jan;162(1):1-10. doi: 10.1530/EJE-09-0597. Epub 2009 Sep 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19776202?dopt=Abstract)
  • Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol. 2009 Nov;5(11):611-9. doi: 10.1038/nrendo.2009.196. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19844248?dopt=Abstract)
  • Saito T, Fukumoto S. Fibroblast Growth Factor 23 (FGF23) and Disorders of Phosphate Metabolism. Int J Pediatr Endocrinol. 2009;2009:496514. doi: 10.1155/2009/496514. Epub 2009 Oct 7. (http://www.ncbi.nlm.nih.gov/pubmed/19956747?dopt=Abstract)
  • Sprecher E. Familial tumoral calcinosis: from characterization of a rare phenotype to the pathogenesis of ectopic calcification. J Invest Dermatol. 2010 Mar;130(3):652-60. doi: 10.1038/jid.2009.337. Epub 2009 Oct 29. (http://www.ncbi.nlm.nih.gov/pubmed/19865099?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2012
Published: December 16, 2014