Human Gene FGF23 (uc001qmq.1) Description and Page Index
Description: fibroblast growth factor 23 precursor RefSeq Summary (NM_020638): This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC). [provided by RefSeq, Feb 2013]. Transcript (Including UTRs) Position: hg18 chr12:4,347,654-4,359,155 Size: 11,502 Total Exon Count: 3 Strand: - Coding Region Position: hg18 chr12:4,349,770-4,359,009 Size: 9,240 Coding Exon Count: 3
ID:FGF23_HUMAN DESCRIPTION: RecName: Full=Fibroblast growth factor 23; Short=FGF-23; AltName: Full=Phosphatonin; AltName: Full=Tumor-derived hypophosphatemia-inducing factor; Contains: RecName: Full=Fibroblast growth factor 23 N-terminal peptide; Contains: RecName: Full=Fibroblast growth factor 23 C-terminal peptide; Flags: Precursor; FUNCTION: Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization. SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors (By similarity). SUBCELLULAR LOCATION: Secreted. Note=Secretion is dependent on O- glycosylation. TISSUE SPECIFICITY: Expressed in osteogenic cells particularly during phases of active bone remodeling. In adult trabecular bone, expressed in osteocytes and flattened bone-lining cells (inactive osteoblasts). PTM: Following secretion this protein is inactivated by cleavage into a N-terminal fragment and a C-terminal fragment. The processing is effected by proprotein convertases. PTM: O-glycosylated by GALT3. Glycosylation is necessary for secretion; it blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated. Competition between proprotein convertase cleavage and block of cleavage by O-glycosylation determines the level of secreted active FGF23. DISEASE: Defects in FGF23 are the cause of autosomal dominant hypophosphataemic rickets (ADHR) [MIM:193100]. ADHR is characterized by low serum phosphorus concentrations, rickets, osteomalacia, leg deformities, short stature, bone pain and dental abscesses. DISEASE: Defects in FGF23 are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:211900]. HFTC is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. SIMILARITY: Belongs to the heparin-binding growth factors family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FGF23"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fgf23/";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): FGF23 CDC HuGE Published Literature: FGF23
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9GZV9
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0006796 phosphate-containing compound metabolic process GO:0008543 fibroblast growth factor receptor signaling pathway GO:0010469 regulation of receptor activity GO:0010966 regulation of phosphate transport GO:0010980 positive regulation of vitamin D 24-hydroxylase activity GO:0018108 peptidyl-tyrosine phosphorylation GO:0030154 cell differentiation GO:0030500 regulation of bone mineralization GO:0030502 negative regulation of bone mineralization GO:0030643 cellular phosphate ion homeostasis GO:0032026 response to magnesium ion GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process GO:0042359 vitamin D metabolic process GO:0042369 vitamin D catabolic process GO:0043687 post-translational protein modification GO:0044267 cellular protein metabolic process GO:0044320 cellular response to leptin stimulus GO:0045668 negative regulation of osteoblast differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0046854 phosphatidylinositol phosphorylation GO:0046888 negative regulation of hormone secretion GO:0051897 positive regulation of protein kinase B signaling GO:0055062 phosphate ion homeostasis GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071305 cellular response to vitamin D GO:0071354 cellular response to interleukin-6 GO:0071374 cellular response to parathyroid hormone stimulus GO:0090080 positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway GO:1904383 response to sodium phosphate