PHEX

Phosphate regulating endopeptidase homolog, X-linked
Identifiers
Symbols	PHEX ; HPDR; HPDR1; HYP; HYP1; LXHR; PEX; XLH
External IDs	OMIM: 300550 MGI: 107489 HomoloGene: 37310 GeneCards: PHEX Gene
EC number	3.4.24.-
Gene ontology Molecular function • aminopeptidase activity • metalloendopeptidase activity • zinc ion binding Cellular component • endoplasmic reticulum • Golgi apparatus • plasma membrane • integral component of plasma membrane • perinuclear region of cytoplasm Biological process • skeletal system development • cellular protein modification process • proteolysis • cell-cell signaling • organophosphate metabolic process • bone mineralization Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5251	18675
Ensembl	ENSG00000102174	ENSMUSG00000057457
UniProt	P78562	P70669
RefSeq (mRNA)	NM_000444	NM_011077
RefSeq (protein)	NP_000435	NP_035207
Location (UCSC)	Chr X: 22.03 – 22.25 Mb	Chr X: 157.16 – 157.42 Mb
PubMed search

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 PHEX gene.^[1][2] This gene contains 18 exons and is located on the X chromosome.

Function

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.^[3] The bone and dentin protein osteopontin (OPN) which inhibits mineralization in the skeleton and in teeth is a substrate for PHEX.^[4] 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.^[5] XLH patients have soft and deformed skeletons and soft teeth that easily become infected.

Clinical significance

Mutation of PHEX leads to X-linked hypophosphatemia.^[1]

References

1. "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. PMID 7550339.
2. 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. PMID 9070861.
3. "Entrez Gene: phosphate regulating endopeptidase homolog".
4. Barros, 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. PMID 22991293.
5. Barros, 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. PMID 22991293.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.