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:
Related Diseases:
References:
1. |
Rothe H et al. (2017) Ecto-5' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients - Data from the German Calciphylaxis Registry.
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2. |
Brame LA et al. (2004) Renal phosphate wasting disorders: clinical features and pathogenesis.
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3. |
Yu X et al. (2005) FGF23 and disorders of phosphate homeostasis.
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4. |
NCBI article
NCBI 8074
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5. |
OMIM.ORG article
Omim 605380
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6. |
Orphanet article
Orphanet ID 121800
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7. |
Wikipedia article
Wikipedia EN (Fibroblast_growth_factor_23)
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Update: Aug. 14, 2020