PHEX

Chr XXLD

phosphate regulating endopeptidase X-linked

Also known as: HPDR, HPDR1, HYP, HYP1, LXHR, PEX, XLH

This transmembrane endopeptidase cleaves ASARM peptides derived from bone matrix proteins, thereby regulating bone and dentin mineralization as well as renal phosphate reabsorption. Mutations cause X-linked hypophosphatemic rickets, which typically presents in early childhood with skeletal deformities, short stature, and dental abnormalities. The gene is highly constrained against loss-of-function variants, indicating mutations are likely to have significant clinical consequences.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismXLDLOEUF 0.141 OMIM phenotype
Clinical SummaryPHEX
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Gene-Disease Validity (ClinGen)
X-linked dominant hypophosphatemic rickets · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — PHEX
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 5.18
OE 0.03 (0.010.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.71Z-score
OE missense 0.72 (0.640.81)
211 obs / 293.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.14)
00.351.4
Missense OE0.72 (0.640.81)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 33.2Missense obs/exp: 211 / 293.4Syn Z: -0.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PHEX · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗