PHEX
Phosphate Regulating Endopeptidase Homolog X-Linked
Gene Information Card
| Symbol | PHEX |
|---|---|
| Full Name | Phosphate Regulating Endopeptidase Homolog X-Linked |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.11 |
| NCBI Gene ID | 5251 ncbi.nlm.nih.gov/gene/5251 |
| Ensembl ID | ENSG00000102174 |
| UniProt ID | P78562 |
| OMIM ID | 300550 |
| HGNC ID | 8918 |
| Aliases | HPDR, HPDR1, XLH, PEX |
Description
The PHEX gene encodes a transmembrane endopeptidase belonging to the M13 family of zinc metallopeptidases. It is primarily expressed in bone and teeth, where it regulates phosphate homeostasis by inactivating fibroblast growth factor 23 (FGF23). Loss-of-function mutations lead to elevated FGF23 levels, causing renal phosphate wasting, hypophosphatemia, and defective bone mineralization.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked hypophosphatemia (XLH) | Loss-of-function mutations in PHEX impair FGF23 degradation, leading to increased FGF23 levels, renal phosphate wasting, and hypophosphatemic rickets/osteomalacia. | ClinVar, OMIM |
| Hypophosphatemic bone disease | Rare PHEX variants cause milder phosphate wasting and bone deformities without classic rickets. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 0.0 | Not detected (nTPM based on GTEx; PHEX is not expressed in bulk RNA-seq of adult tissues, but is active in osteoblasts and odontoblasts) |
| Lung | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblast (primary) | N/A | High expression; key site of PHEX activity |
| Odontoblast (primary) | N/A | High expression; involved in dentin mineralization |
| HEK293 | N/A | Low/absent; used for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.223C>T (p.Arg75*) | Nonsense | ~10% of XLH families | Premature stop; loss of function |
| c.1601C>T (p.Pro534Leu) | Missense | ~5% of XLH families | Impaired catalytic activity; loss of function |
| c.871_872del (p.Leu291Glufs*2) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most PHEX mutations are loss-of-function, leading to reduced FGF23 cleavage and elevated FGF23 levels.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not applicable; X-linked recessive inheritance with skewed X-inactivation in females.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity (GO:0004222) | • plasma membrane (GO:0005886) |
| • proteolysis (GO:0006508) | • bone mineralization (GO:0030282) |
| • cellular phosphate ion homeostasis (GO:0030643) |
Pathways
• FGF23 signaling pathway (Reactome: R-HSA-8853659)
• Vitamin D metabolism (Reactome: R-HSA-196791)
Protein Summary
PHEX is a 749-amino acid type II transmembrane glycoprotein with a short N-terminal cytoplasmic tail, a transmembrane domain, and a large extracellular domain containing the zinc-binding motif HExxH. It is expressed on the surface of osteoblasts and odontoblasts, where it cleaves and inactivates FGF23, a key phosphaturic hormone. Loss of PHEX activity results in FGF23 accumulation, leading to renal phosphate wasting and hypophosphatemic rickets.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHEX Knockout HEK293 Cell Line | EDJ-KQ2951 | Human | 5251 | Details Get a Quote |
| PHEX Knockout HeLa Cell Line | EDJ-KQ24086 | Human | 5251 | Details Get a Quote |
| PHEX Knockout A-549 Cell Line | EDJ-KQ62624 | Human | 5251 | Details Get a Quote |
| PHEX Knockout HCT 116 Cell Line | EDJ-KQ71095 | Human | 5251 | Details Get a Quote |
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