PHEX : phosphate regulating endopeptidase X-linked
Description
The PHEX (phosphate regulating endopeptidase X-linked) is a protein-coding gene located on chromosome X.
The PHEX gene provides instructions for making an enzyme primarily active in bones and teeth. This enzyme likely cleaves other proteins into smaller pieces, though the specific proteins it targets remain unidentified. The PHEX enzyme may regulate phosphate balance in the body, a mineral crucial for bone formation and growth during childhood and maintaining bone strength in adulthood. Phosphate levels are largely controlled by the kidneys, which excrete excess phosphate in urine and reabsorb it when needed. Studies suggest the PHEX enzyme could be involved in regulating fibroblast growth factor 23 (FGF23) activity, a protein that inhibits phosphate reabsorption by the kidneys. While the exact mechanism is unknown, the PHEX enzyme seems to influence FGF23, though a direct link is yet to be established. The exact role of PHEX in phosphate reabsorption and bone formation remains unclear.
PHEX is an enzyme that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, regulating their biological activity. It cleaves ASARM peptides between Ser and Glu or Asp residues. PHEX regulates osteogenic cell differentiation and bone mineralization by cleaving the MEPE-derived ASARM peptide. It promotes dentin mineralization and renal phosphate reabsorption by cleaving DMP1- and MEPE-derived ASARM peptides. Additionally, PHEX inhibits the cleavage of MEPE by CTSB/cathepsin B, preventing MEPE degradation. PHEX interacts with MEPE in a zinc-dependent manner via the ASARM motif.
PHEX is also known as HPDR, HPDR1, HYP, HYP1, LXHR, PEX, XLH.
Associated Diseases
- Hypophosphatemic rickets, X-linked dominant
- X-linked hypophosphatemia
- Hereditary hypophosphatemic rickets
