FGF23
Fibroblast Growth Factor 23: A Key Regulator of Phosphate and Vitamin D Metabolism
Gene Information Card
| Symbol | FGF23 |
|---|---|
| Full Name | Fibroblast Growth Factor 23 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.32 |
| NCBI Gene ID | 8074 ncbi.nlm.nih.gov/gene/8074 |
| Ensembl ID | ENSG00000118972 |
| UniProt ID | Q9GZV9 |
| OMIM ID | 605380 |
| HGNC ID | 3680 |
| Aliases | ADHR, FGFN, HPDR2, HYPF, PHPTC |
Description
FGF23 encodes a member of the fibroblast growth factor family that functions as a key endocrine regulator of phosphate homeostasis and vitamin D metabolism. The protein is secreted primarily by osteocytes and acts on the kidney to reduce phosphate reabsorption and suppress 1,25-dihydroxyvitamin D production. Mutations in FGF23 cause autosomal dominant hypophosphatemic rickets (ADHR) and are associated with tumor-induced osteomalacia (oncogenic osteomalacia).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant hypophosphatemic rickets (ADHR) | Gain-of-function mutations in FGF23 (e.g., R176Q, R179W) prevent proteolytic cleavage, leading to elevated intact FGF23 and renal phosphate wasting. | OMIM #193100; NCBI Gene; ClinVar |
| X-linked hypophosphatemia (XLH) | While primarily caused by PHEX mutations, secondary FGF23 elevation contributes to hypophosphatemia. | OMIM #307800; NCBI Gene |
| Tumor-induced osteomalacia (oncogenic osteomalacia) | Overexpression of FGF23 by mesenchymal tumors causes renal phosphate wasting and low vitamin D. | OMIM #605380; NCBI Gene |
| Familial tumoral calcinosis (hyperphosphatemia) | Loss-of-function mutations in FGF23 (e.g., S71G, M96T) lead to reduced FGF23 activity, causing hyperphosphatemia and ectopic calcification. | OMIM #211900; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone (osteocytes) | 0.2 | Low |
| Kidney | 0.1 | Low |
| Heart | 0.1 | Low |
| Liver | 0.1 | Low |
| Skeletal muscle | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteocyte cell lines (e.g., IDG-SW3) | 0.5 | Moderate expression under differentiation |
| HEK293 (transfected) | N/A | Used for recombinant FGF23 studies |
| Saos-2 (osteosarcoma) | 0.2 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.527G>A (p.R176Q) | Missense | Rare | Gain-of-function; prevents furin cleavage; causes ADHR |
| c.535C>T (p.R179W) | Missense | Rare | Gain-of-function; prevents furin cleavage; causes ADHR |
| c.211A>G (p.S71G) | Missense | Rare | Loss-of-function; causes familial tumoral calcinosis |
| c.287T>C (p.M96T) | Missense | Rare | Loss-of-function; causes familial tumoral calcinosis |
Mutation functional classification
Loss of Function (LOF)
Mutations such as S71G and M96T reduce FGF23 activity, leading to hyperphosphatemia and familial tumoral calcinosis.
Gain of Function (GOF)
Mutations such as R176Q and R179W stabilize intact FGF23 by blocking proteolytic cleavage, causing hypophosphatemia in ADHR.
Dominant Negative (DN)
No dominant-negative mutations have been reported for FGF23.
View complete mutation data：
Gene Ontology (GO)
| • growth factor activity (GO:0008083) | • signaling receptor binding (GO:0005102) |
| • protein binding (GO:0005515) | • bone mineralization (GO:0030282) |
| • cellular phosphate ion homeostasis (GO:0030643) | • regulation of bone remodeling (GO:0046850) |
| • branching involved in labyrinthine layer morphogenesis (GO:0060670) |
Pathways
• FGF23 signaling pathway (Reactome: R-HSA-190236)
• Vitamin D metabolism (Reactome: R-HSA-196791)
• Phosphate homeostasis (KEGG: hsa04978)
Protein Summary
FGF23 is a 251-amino acid secreted glycoprotein that undergoes proteolytic cleavage between residues 176 and 179 to generate inactive N- and C-terminal fragments. The intact, active form binds to FGFR-Klotho complexes in the kidney to inhibit phosphate reabsorption and reduce 1,25-dihydroxyvitamin D synthesis. It is primarily expressed in osteocytes and plays a central role in bone-kidney endocrine crosstalk.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGF23 Knockout HEK293 Cell Line | EDJ-KQ662 | Human | 8074 | Details Get a Quote |
| FGF23 Knockout HeLa Cell Line | EDJ-KQ18297 | Human | 8074 | Details Get a Quote |
| FGF23 Knockout A-549 Cell Line | EDJ-KQ63309 | Human | 8074 | Details Get a Quote |
| FGF23 Knockout HCT 116 Cell Line | EDJ-KQ71779 | Human | 8074 | Details Get a Quote |
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