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Gene Review

FGF23  -  fibroblast growth factor 23

Homo sapiens

Synonyms: ADHR, FGF-23, FGFN, Fibroblast growth factor 23, HPDR2, ...
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Disease relevance of FGF23


Psychiatry related information on FGF23


High impact information on FGF23


Chemical compound and disease context of FGF23


Biological context of FGF23

  • Sequencing revealed a homozygous missense mutation in the FGF23 gene (p.S71G) at an amino acid position which is conserved from fish to man [1].
  • The FTC phenotype is regarded as the metabolic mirror image of hypophosphatemic conditions, where causal mutations are known in genes FGF23 or PHEX [1].
  • Intergenic conserved region (IGCR) within the FGF6-FGF23 gene cluster was identified based on the evolutionary conservation [15].
  • The FGF23 has also been implicated in autosomal dominant hypophosphatemic rickets, in which a gene mutation results in production of abnormal FGF23 that resists hydrolysis [16].
  • To better define the precise role of FGF-23 in maintaining Pi balance and bone mineralization, we generated transgenic mice that express wild-type human FGF-23, under the control of the alpha1(I) collagen promoter, in cells of the osteoblastic lineage [17].

Anatomical context of FGF23

  • Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states [18].
  • Long-term bone marrow stromal cell cultures supplemented with 10 mu M ASARM-PO(4) peptide resulted in significant elevation of FGF23 transcripts and inhibition of mineralization [19].
  • Recent evidence that FGF-23 is expressed in mesenchymal tumors associated with OOM suggests that FGF-23 is responsible for the phosphaturic activity previously termed "phosphatonin." Here we show that both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells [20].
  • BACKGROUND: The gene for the renal phosphate wasting disorder autosomal-dominant hypophosphatemic rickets (ADHR) is FGF23, which encodes a secreted protein related to the fibroblast growth factors (FGFs) [21].
  • We also show that FGF23 induces tyrosine phosphorylation and inhibits sodium-phosphate cotransporter Npt2a mRNA expression using opossum kidney cells, a model kidney proximal tubule cell line [22].

Associations of FGF23 with chemical compounds


Enzymatic interactions of FGF23


Regulatory relationships of FGF23

  • FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate [20].
  • Silencing GALNT3 resulted in enhanced processing of FGF23 [27].
  • FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr-1 [28].

Other interactions of FGF23

  • Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively [29].
  • To clarify the signaling mechanisms of FGF23 that mediate the reduction of Pi reabsorption, we inhibited the function of the known FGFRs in opossum kidney (OK-E) cells by expressing a dominant-negative (DN) form of FGFR [30].
  • To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases [18].
  • The FGF23 concentrations were not elevated in patients with primary hyperparathyroidism compared with healthy controls [23].
  • Studies mostly performed in rodents and chicken have demonstrated that FGF18 is a pleiotropic growth factor involved in the development of various organs, while there are no data supporting a direct role of FGF23 in cell proliferation or differentiation either in physiology or pathology in any species [6].

Analytical, diagnostic and therapeutic context of FGF23

  • FGF23 circulates in the bloodstream, and animal models demonstrate that FGF23 controls phosphate and Vitamin D homeostasis through the regulation of specific renal proteins [2].
  • METHODS: Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD) [3].
  • Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects [3].
  • Sequence analyses of the PHEX and FGF23 genes were normal [31].
  • Expression of FGF23 mRNA in human osteoblast-like bone cells, quantitated by real-time RT-PCR, increased with increasing extracellular phosphate and was 2-fold higher in cells treated with 2 mM extracellular phosphate compared to 0 mM phosphate treatment [32].


  1. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Benet-Pagès, A., Orlik, P., Strom, T.M., Lorenz-Depiereux, B. Hum. Mol. Genet. (2005) [Pubmed]
  2. FGF23 and disorders of phosphate homeostasis. Yu, X., White, K.E. Cytokine Growth Factor Rev. (2005) [Pubmed]
  3. Serum FGF23 levels in normal and disordered phosphorus homeostasis. Weber, T.J., Liu, S., Indridason, O.S., Quarles, L.D. J. Bone Miner. Res. (2003) [Pubmed]
  4. FGF23 concentrations vary with disease status in autosomal dominant hypophosphatemic rickets. Imel, E.A., Hui, S.L., Econs, M.J. J. Bone Miner. Res. (2007) [Pubmed]
  5. Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. Wesseling-Perry, K., Pereira, R.C., Wang, H., Elashoff, R.M., Sahney, S., Gales, B., Jüppner, H., Salusky, I.B. J. Clin. Endocrinol. Metab. (2009) [Pubmed]
  6. Expression of fibroblast growth factors 18 and 23 during human embryonic and fetal development. Cormier, S., Leroy, C., Delezoide, A.L., Silve, C. Gene Expr. Patterns (2005) [Pubmed]
  7. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Feng, J.Q., Ward, L.M., Liu, S., Lu, Y., Xie, Y., Yuan, B., Yu, X., Rauch, F., Davis, S.I., Zhang, S., Rios, H., Drezner, M.K., Quarles, L.D., Bonewald, L.F., White, K.E. Nat. Genet. (2006) [Pubmed]
  8. The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23. White, K.E., Larsson, T.E., Econs, M.J. Endocr. Rev. (2006) [Pubmed]
  9. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. Masuyama, R., Stockmans, I., Torrekens, S., Van Looveren, R., Maes, C., Carmeliet, P., Bouillon, R., Carmeliet, G. J. Clin. Invest. (2006) [Pubmed]
  10. Role of fibroblast growth factor 23 in health and in chronic kidney disease. Fukagawa, M., Nii-Kono, T., Kazama, J.J. Curr. Opin. Nephrol. Hypertens. (2005) [Pubmed]
  11. The phosphatonins and the regulation of phosphate transport and vitamin D metabolism. Sommer, S., Berndt, T., Craig, T., Kumar, R. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  12. A case of oncogenic osteomalacia with preoperative secondary hyperparathyroidism: Description of the biochemical response of FGF23 to octreotide therapy and surgery. Elston, M.S., Stewart, I.J., Clifton-Bligh, R., Conaglen, J.V. Bone (2007) [Pubmed]
  13. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. Gutierrez, O., Isakova, T., Rhee, E., Shah, A., Holmes, J., Collerone, G., Jüppner, H., Wolf, M. J. Am. Soc. Nephrol. (2005) [Pubmed]
  14. The Role of Mutant UDP-N-Acetyl-{alpha}-D-Galactosamine-Polypeptide N-Acetylgalactosaminyltransferase 3 in Regulating Serum Intact Fibroblast Growth Factor 23 and Matrix Extracellular Phosphoglycoprotein in Heritable Tumoral Calcinosis. Garringer, H.J., Fisher, C., Larsson, T.E., Davis, S.I., Koller, D.L., Cullen, M.J., Draman, M.S., Conlon, N., Jain, A., Fedarko, N.S., Dasgupta, B., White, K.E. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  15. Comparative genomics on mammalian Fgf6-Fgf23 locus. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2005) [Pubmed]
  16. Phosphate diabetes, tubular phosphate reabsorption and phosphatonins. Laroche, M., Boyer, J.F. Joint, bone, spine : revue du rhumatisme. (2005) [Pubmed]
  17. Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Larsson, T., Marsell, R., Schipani, E., Ohlsson, C., Ljunggren, O., Tenenhouse, H.S., Jüppner, H., Jonsson, K.B. Endocrinology (2004) [Pubmed]
  18. Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Bai, X., Miao, D., Li, J., Goltzman, D., Karaplis, A.C. Endocrinology (2004) [Pubmed]
  19. Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity. Liu, S., Rowe, P.S., Vierthaler, L., Zhou, J., Quarles, L.D. J. Endocrinol. (2007) [Pubmed]
  20. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Bowe, A.E., Finnegan, R., Jan de Beur, S.M., Cho, J., Levine, M.A., Kumar, R., Schiavi, S.C. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  21. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. White, K.E., Carn, G., Lorenz-Depiereux, B., Benet-Pages, A., Strom, T.M., Econs, M.J. Kidney Int. (2001) [Pubmed]
  22. Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23. Yu, X., Ibrahimi, O.A., Goetz, R., Zhang, F., Davis, S.I., Garringer, H.J., Linhardt, R.J., Ornitz, D.M., Mohammadi, M., White, K.E. Endocrinology (2005) [Pubmed]
  23. Fibroblast growth factor 23, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D in surgically treated primary hyperparathyroidism. Tebben, P.J., Singh, R.J., Clarke, B.L., Kumar, R. Mayo Clin. Proc. (2004) [Pubmed]
  24. Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Nagano, N., Miyata, S., Abe, M., Kobayashi, N., Wakita, S., Yamashita, T., Wada, M. Kidney Int. (2006) [Pubmed]
  25. Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are differentially processed. Larsson, T., Davis, S.I., Garringer, H.J., Mooney, S.D., Draman, M.S., Cullen, M.J., White, K.E. Endocrinology (2005) [Pubmed]
  26. 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. Campos, M., Couture, C., Hirata, I.Y., Juliano, M.A., Loisel, T.P., Crine, P., Juliano, L., Boileau, G., Carmona, A.K. Biochem. J. (2003) [Pubmed]
  27. Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of o-glycosylation associated with augmented processing of fibroblast growth factor 23. Frishberg, Y., Ito, N., Rinat, C., Yamazaki, Y., Feinstein, S., Urakawa, I., Navon-Elkan, P., Becker-Cohen, R., Yamashita, T., Araya, K., Igarashi, T., Fujita, T., Fukumoto, S. J. Bone Miner. Res. (2007) [Pubmed]
  28. FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr-1. Fukuda, T., Kanomata, K., Nojima, J., Urakawa, I., Suzawa, T., Imada, M., Kukita, A., Kamijo, R., Yamashita, T., Katagiri, T. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  29. Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait. Goji, K., Ozaki, K., Sadewa, A.H., Nishio, H., Matsuo, M. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  30. Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cells. Yan, X., Yokote, H., Jing, X., Yao, L., Sawada, T., Zhang, Y., Liang, S., Sakaguchi, K. Genes Cells (2005) [Pubmed]
  31. Resolution of severe, adolescent-onset hypophosphatemic rickets following resection of an FGF-23-producing tumour of the distal ulna. Ward, L.M., Rauch, F., White, K.E., Filler, G., Matzinger, M.A., Letts, M., Travers, R., Econs, M.J., Glorieux, F.H. Bone (2004) [Pubmed]
  32. Bone as a source of FGF23: regulation by phosphate? Mirams, M., Robinson, B.G., Mason, R.S., Nelson, A.E. Bone (2004) [Pubmed]
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