Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Fibroblast growth factor 23

The FGF23 gene encodes an important hormone of phosphate and vitamin D metabolism. Hight serum levels of FGF23 cause hyperphosphaturia while low levels lead to hyperphosphatemia. Mutations of this gene are associated with either autosomal dominant hypophosphatemic rickets (gain-of-function) or recessive hypophosphatemic familial tumoral calcinosis (loss-of-function).

Protein Structure

The FGF23 protein consists of 251 amino acids and its molecular weight is about 32kD. The N-terminal portion binds to the FGF receptors (FGFR1-4) and the C-terminal domain binds to klotho.

Gene Regulation

FGF23 is produced by osteoblasts in the bone. Synthesis and secretion is stimulated by parathyroid hormone, calcitriol, hight dietary phosphate intake, and hyperphosphatemia. The production is inhibited by proteins encoded by the genes DMP1 and PHEX.

The proximal tubular cell is the main target of FGF23. Its receptor is a complex of FGF receptor and klotho located in the basolateral membrane. If bound FGF23 elicits a signal cascade the finally has the following physiological results:

  • Reduction of the number of phosphate tranporters in the luminal membrane causing reduced phosphate reabsorption.
  • Reduction of 1 alpha hydroxylase (CYP27B1) activity causing reduced production of calcitriol.
  • Activation of 24 hydroxylase (CYP24A1) causing enhanced inactivation of calcitriol to calcitroic acid.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 10 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 10 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Autosomal dominant hypophosphatemic rickets
FGF23
Hyperphosphatemic familial tumoral calcinosis
FGF23
GALNT3
KL

References:

1.

Brame LA et al. (2004) Renal phosphate wasting disorders: clinical features and pathogenesis.

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2.

Yu X et al. (2005) FGF23 and disorders of phosphate homeostasis.

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Update: Sept. 26, 2018