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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)
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
General
fibroblast growth factor
glycoprotein
Properties
SIZE: entity length = 251 aa
MW = 28 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-24}
cysteine residue {C95}
MODIFICATION: cysteine residue {C113}
cysteine residue {C113}
MODIFICATION: cysteine residue {C95}
Thr glycosylation site {T178}
proteolytic site {179-180}
SECRETED-BY: endothelial cell
Database Correlations
OMIM correlations
MORBIDMAP 605380
UniProt Q9GZV9
Pfam PF00167
Entrez Gene 8074
Kegg hsa:8074
References
- UniProt :accession Q9GZV9
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/FGF23
- NIEHS-SNPs
http://egp.gs.washington.edu/data/fgf23/
- 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: 29516098
https://jamanetwork.com/journals/jamacardiology/fullarticle/2673604
- Medical Knowledge Self Assessment Program (MKSAP) 17, 19
American College of Physicians, Philadelphia 2015, 2021