Phosphate-regulating neutral endopeptidase, X-linked also known as phosphate-regulating gene with homologies to endopeptidases on the X chromosome or metalloendopeptidase homolog PEX is an enzyme that in humans is encoded by the PHEXgene. This gene contains 18 exons and is located on the X chromosome.
The protein encoded by this gene is a transmembrane endopeptidase that belongs to the type II integral membrane zinc-dependent endopeptidase family. The protein is thought to be involved in bone and dentin mineralization and renal phosphate reabsorption. The bone and dentin protein osteopontin (OPN) which inhibits mineralization in the skeleton and in teeth is a substrate for PHEX. In the absence of functional PHEX in the mouse model (Hyp) of X-linked hypophosphatemia, in addition to renal phosphate wasting, osteopontin and osteopontin fragments accumulate in bone and may contribute to the osteomalacia characteristic of XLH/HYP. XLH patients have soft and deformed skeletons and soft teeth that easily become infected.
^ ab"A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets (XLH/HYP). The HYP Consortium". Nat. Genet. 11 (2): 130–6. October 1995. doi:10.1038/ng1095-130. PMID7550339.
^Grieff M, Mumm S, Waeltz P, Mazzarella R, Whyte MP, Thakker RV, Schlessinger D (February 1997). "Expression and cloning of the human X-linked hypophosphatemia gene cDNA". Biochem. Biophys. Res. Commun. 231 (3): 635–9. doi:10.1006/bbrc.1997.6153. PMID9070861.
^ abBarros, NMT; et al. (2013). "Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia". Journal of Bone and Mineral Research. 28 (3): 688–699. doi:10.1002/jbmr.1766. PMID22991293.