fibroblast growth factor 23; FGF-23; phosphatonin; tumor-derived hypophosphatemia-inducing factor; contains: fibroblast growth factor 23 N-terminal peptide; fibroblast growth factor 23 C-terminal peptide (FGF23, HYPF, UNQ3027/PRO9828)
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Function
- regulator of phosphate homeostasis
- elevated plasma FGF-23 enhances phosphate secretion[5]
- inhibits renal tubular phosphate transport by reducing SLC34A1 levels
- uregulates EGR1 expression in the presence of KL (putative)
- acts directly on the parathyroid to decrease PTH secretion
- reduces vitamin-D activation to 1,25-dihydroxyvitamin D by the renal tubules
- negatively regulates osteoblast differentiation & matrix mineralization
- following secretion, FGF23 is inactivated by cleavage into a N-terminal fragment & a C-terminal fragment
- processing is effected by proprotein convertases
- O-glycosylated by GALT3
- glycosylation is necessary for secretion
- glycosylation blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated
- competition between proprotein convertase cleavage & block of cleavage by O-glycosylation determines the level of secreted active FGF23
- interacts with FGFR1, FGFR2, FGFR3 & FGFR4
- affinity between fibroblast growth factors (FGFs) & their receptors is increased by KL & heparan sulfate glycosaminoglycans that function as coreceptors (putative)
Structure
- belongs to the heparin-binding growth factors family
Compartment
- secreted
- secretion is dependent on O-glycosylation
Expression
- expressed in osteogenic cells particularly during phases of active bone remodeling
- in adult trabecular bone, expressed in osteocytes & flattened bone-lining cells (inactive osteoblasts)
Pathology
- defects in FGF23 are the cause of autosomal dominant hypophosphataemic rickets
- defects in FGF23 are a cause of hyperphosphatemic familial tumoral calcinosis
- higher plasma FGF-23 associated with increased risk for coronary artery disease[4]
- overexpression of FGF-23 by benign mesenchymal tumors of vascular or skeletal origin results in impaired resorption of phosphate in renal tubules & decreased synthesis of calcitriol leading to hypophosphatemia & oncogenic osteomalacia[5]
- role in renal osteodystrophy
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9GZV9.html
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/FGF23
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/fgf23/
- ↑ 4.0 4.1 Panwar B, Judd SE, Wadley VG et al Association of Fibroblast Growth Factor 23 With Risk of Incident Coronary Heart Disease in Community-Living Adults. JAMA Cardiol. Published online March 7, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29516098 https://jamanetwork.com/journals/jamacardiology/fullarticle/2673604
- ↑ 5.0 5.1 5.2 Medical Knowledge Self Assessment Program (MKSAP) 17, 19 American College of Physicians, Philadelphia 2015, 2021
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8074
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8074
- OMIM: https://mirror.omim.org/entry/193100
- OMIM: https://mirror.omim.org/entry/211900
- OMIM: https://mirror.omim.org/entry/605380
- UniProt: http://www.uniprot.org/uniprot/Q9GZV9.html