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The PHEX gene, named to signify Phosphate regulating gene with Homologies to Endopeptidases located on the X chromosome, was identified in 1995 as the gene disrupted in X-Linked Hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets (1). XLH is inherited in an X-Linked dominant pattern and shows complete penetrance in both males and females (2, 3). Patients experience lifelong symptoms resulting from chronic hypophosphatemia including impaired bone mineralization, rickets, skeletal deformities, growth retardation and diminished quality of life (4-6). For more information on XLH see: About XLH.
The PHEX gene has 22 exons spanning ~220kb and encodes a 749 amino acid protein with homology to M13 zinc metallopeptidases (1). In various in vitro assays, the PHEX protein has been shown to cleave putative target proteins at ASARM peptide motifs, but the physiological protein targets for PHEX cleavage are not known (7, 8).
PHEX is primarily expressed in bone and teeth where it is thought to promote mineralization by indirectly regulating the expression of the phosphate regulating hormone fibroblast growth factor 23 (FGF23) (9). PHEX is also proposed to play a role in bone and tooth mineralization that is independent of FGF23/phosphate regulation, possibly through the bone matrix protein Osteopontin (10).
More than 800 disease-causing variants in the PHEX gene have been identified in XLH patients and are represented in this Locus Specific Database (12). The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants. All of the variants are predicted to lead to a loss of PHEX protein function.
Largest locus specific database for PHEX gene mutation PHEX gene in charge of Phosphate regulation on the X chromosome X-Linked Hypophosphatemia Hypophosphatemia ricket XLH known to be related to PHEX mutation chronic hypophosphatemia impaired bone mineralization skeletal deformities growth retardation