Fibroblast growth factor 23

PDB rendering based on 2p39.

Available structures
PDB	2p39

Identifiers

Symbols

FGF23; ADHR; HPDR2; HYPF; PHPTC

External IDs

OMIM: 605380 MGI: 1891427 HomoloGene: 10771 GeneCards: FGF23 Gene

Gene Ontology
Molecular function	• type 1 fibroblast growth factor receptor binding • growth factor activity
Cellular component	• extracellular region • extracellular region • extracellular space • extracellular space
Biological process	• phosphate metabolic process • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • fibroblast growth factor receptor signaling pathway • regulation of phosphate transport • positive regulation of vitamin D 24-hydroxylase activity • cell differentiation • negative regulation of bone mineralization • cellular phosphate ion homeostasis • vitamin D catabolic process • negative regulation of osteoblast differentiation • negative regulation of hormone secretion • phosphate ion homeostasis • positive regulation of ERK1 and ERK2 cascade • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
4.48 – 4.49 Mb

Chr 6:
127.02 – 127.03 Mb

PubMed search

[1]

[2]

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene.^[1] FGF23 is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate metabolism.^[2]

1 Function
2 Clinical signficance
3 References
4 Further reading

Function

FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The product of this gene inhibits renal tubular phosphate transport. FGF23 is known as a phosphaturic hormone, in that it inhibits renal reabsorption of phosphate in the kidney, mostly in the proximal convoluted tubule. FGF23 is mostly expressed in bone and connective tissue and prior to 2000 was known in the scientific community as phosphatonin. The factor itself was hypothesized following case studies of hypophosphatemic diseases such as X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and (tumor induced) oncogenic osteomalacia. Also, FGF23 inhibits 1-hydroxylase. 1-hydroxylase is responsible for the conversion of calcifediol to calcitriol (the biologically active form of Vitamin D).

Clinical signficance

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.^[3] 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.^[4] Prior to discovery in 2000, it was hypothesized that a protein existed which performed the function of FGF23. This putative protein was known as phosphatonin.

References

^ 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.
^ 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.
^ Zadik Y, Nitzan DW (October 2011). "Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?". Oral Oncol. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764.
^ "Entrez Gene: FGF23 fibroblast growth factor 23". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8074.

Kiela PR, Ghishan FK (January 2009). "Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis". Lab. Invest. 89 (1): 7–14. doi:10.1038/labinvest.2008.114. PMID 19029978.
Silve C, Beck L (2003). "Is FGF23 the long sought after phosphaturic factor phosphatonin?". Nephrol. Dial. Transplant. 17 (6): 958–61. doi:10.1093/ndt/17.6.958. PMID 12032180.
Quarles LD (2003). "FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.". Am. J. Physiol. Endocrinol. Metab. 285 (1): E1–9. doi:10.1152/ajpendo.00016.2003. PMID 12791601.
Fukagawa M, Nii-Kono T, Kazama JJ (2005). "Role of fibroblast growth factor 23 in health and in chronic kidney disease.". Curr. Opin. Nephrol. Hypertens. 14 (4): 325–9. doi:10.1097/01.mnh.0000172717.49476.80. PMID 15930999.
Imel EA, Econs MJ (2006). "Fibroblast growth factor 23: roles in health and disease.". J. Am. Soc. Nephrol. 16 (9): 2565–75. doi:10.1681/ASN.2005050573. PMID 16033853.
Liu S, Quarles LD (2007). "How fibroblast growth factor 23 works.". J. Am. Soc. Nephrol. 18 (6): 1637–47. doi:10.1681/ASN.2007010068. PMID 17494882.
Econs, Michael J.; Strom, Tim M.; White, Kenneth E.; Evans, Wayne E.; O'Riordan, Jeffery L.H.; Speer, Marcy C.; Lorenz-Depiereux, Bettina; Grabowski, Monika et al. (2000). "Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.". Nat. Genet. 26 (3): 345–8. doi:10.1038/81664. PMID 11062477.
White KE, Jonsson KB, Carn G, et al. (2001). "The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting.". J. Clin. Endocrinol. Metab. 86 (2): 497–500. doi:10.1210/jc.86.2.497. PMID 11157998.
Shimada T, Mizutani S, Muto T, et al. (2001). "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6500–5. doi:10.1073/pnas.101545198. PMC 33497. PMID 11344269. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=33497.
Bowe AE, Finnegan R, Jan de Beur SM, et al. (2001). "FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate.". Biochem. Biophys. Res. Commun. 284 (4): 977–81. doi:10.1006/bbrc.2001.5084. PMID 11409890.
White KE, Carn G, Lorenz-Depiereux B, et al. (2002). "Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23.". Kidney Int. 60 (6): 2079–86. doi:10.1046/j.1523-1755.2001.00064.x. PMID 11737582.
Kruse K, Woelfel D, Strom TM, Storm TM (2002). "Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation.". Horm. Res. 55 (6): 305–8. doi:10.1159/000050018. PMID 11805436.
Yamashita T, Konishi M, Miyake A, et al. (2002). "Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway.". J. Biol. Chem. 277 (31): 28265–70. doi:10.1074/jbc.M202527200. PMID 12032146.
Saito H, Kusano K, Kinosaki M, et al. (2003). "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production.". J. Biol. Chem. 278 (4): 2206–11. doi:10.1074/jbc.M207872200. PMID 12419819.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Bai XY, Miao D, Goltzman D, Karaplis AC (2003). "The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency.". J. Biol. Chem. 278 (11): 9843–9. doi:10.1074/jbc.M210490200. PMID 12519781.
Larsson T, Zahradnik R, Lavigne J, et al. (2003). "Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia.". Eur. J. Endocrinol. 148 (2): 269–76. doi:10.1530/eje.0.1480269. PMID 12590648.
Campos M, Couture C, Hirata IY, et al. (2003). "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.". Biochem. J. 373 (Pt 1): 271–9. doi:10.1042/BJ20030287. PMC 1223479. PMID 12678920. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223479.

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

PDB gallery

2p39: Crystal structure of human FGF23

Growth factors

Fibroblast	FGF receptor ligands: FGF1/FGF2/FGF5 · FGF3/FGF4/FGF6 · KGF (FGF7/FGF10/FGF22) · FGF8/FGF17/FGF18 · FGF9/FGF16/FGF20 FGF homologous factors: FGF11 · FGF12 · FGF13 · FGF14 hormone-like: FGF19 · FGF21 · FGF23

EGF-like domain	TGF-α · EGF · HB-EGF

TGFβ pathway	TGF-β (TGF-β1, TGF-β2, TGF-β3)

Insulin-like	IGF-1 · IGF-2

Platelet-derived	PDGFA · PDGFB · PDGFC · PDGFD

Vascular endothelial	VEGF-A · VEGF-B · VEGF-C · VEGF-D · PGF

Other	Nerve · Hepatocyte

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Fibroblast growth factor 23

Contents

Function

Clinical signficance

References

Further reading