X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets and osteomalacia, hypophosphataemia, and aberrant renal Pi reabsorption and vitamin D metabolism (Tenenhouse, 1999). Of special interest is the identification of a gene (PEX) that is mutated in X-linked hypophosphatemic patients (Grieff 1997).
PEX encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. Several mutations of this gene in human are described by Dixon et al. (1998).
PEX mRNA was found in a restricted pattern, predominantly in adult ovary and fetal lung. A PEX cDNA of 2550 basepairs, which contains the full PEX coding region, was isolated from a human ovary cDNA library. The PEX cDNA shows high homology to other membrane-bound zinc metallopeptidases (Grieff et al., 1997)
General function
Metabolism, Hydrolase, Peptidase/Protease
Comment
Studies in murine Hyp and Gy homologues (X-linked Hypophosphatemia) have identified a specific defect in Na+-Pi cotransport at the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) synthesis and degradation, and an intrinsic defect in bone mineralization (Tenenhouse, 1999).
Recombinant PEX can function as an endopeptidase (Lipman et al, 1998). Based on its homology to endopeptidases, it is postulated that PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s) which plays a key role in the regulation of bone mineralization, renal Pi handling and vitamin D metabolism (Tenenhouse, 1999).