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Genetics Home Reference: your guide to understanding genetic conditions
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PHEX

Reviewed September 2010

What is the official name of the PHEX gene?

The official name of this gene is “phosphate regulating endopeptidase homolog, X-linked.”

PHEX is the gene's official symbol. The PHEX gene is also known by other names, listed below.

What is the normal function of the PHEX gene?

The PHEX gene provides instructions for making an enzyme that is active primarily in bones and teeth. Studies suggest that it cuts (cleaves) other proteins into smaller pieces; however, the proteins cleaved by the PHEX enzyme have not been identified.

The PHEX enzyme could be involved in regulating the balance of phosphate in the body. Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally excrete excess phosphate in urine, and they reabsorb this mineral into the bloodstream when more is needed.

Studies suggest that the PHEX enzyme may be involved in the regulation of a protein called fibroblast growth factor 23 (which is produced from the FGF23 gene). This protein normally inhibits the kidneys' ability to reabsorb phosphate into the bloodstream. Although the PHEX enzyme is thought to have some effect on the activity of fibroblast growth factor 23, no direct link has been established. It remains unclear how the PHEX enzyme helps control phosphate reabsorption and what role it plays in the formation and growth of bones.

How are changes in the PHEX gene related to health conditions?

hereditary hypophosphatemic rickets - caused by mutations in the PHEX gene

More than 200 mutations in the PHEX gene have been found to cause the most common form of hereditary hypophosphatemic rickets, which is known as X-linked hypophosphatemic rickets. These mutations inactivate the PHEX enzyme, leaving it unable to cleave other proteins.

Researchers are uncertain how mutations in the PHEX gene lead to low levels of phosphate in the blood (hypophosphatemia) and related problems with bone growth in people with X-linked hypophosphatemic rickets. Because many affected individuals have increased levels of fibroblast growth factor 23, it is likely that PHEX gene mutations somehow alter the production of that protein. An increase in fibroblast growth factor 23 reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia. However, because some affected individuals have normal levels of fibroblast growth factor 23, researchers are also considering other pathways by which a mutated PHEX gene could result in X-linked hypophosphatemic rickets.

Where is the PHEX gene located?

Cytogenetic Location: Xp22.2-p22.1

Molecular Location on the X chromosome: base pairs 22,050,920 to 22,266,477

The PHEX gene is located on the short (p) arm of the X chromosome between positions 22.2 and 22.1.

The PHEX gene is located on the short (p) arm of the X chromosome between positions 22.2 and 22.1.

More precisely, the PHEX gene is located from base pair 22,050,920 to base pair 22,266,477 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PHEX?

You and your healthcare professional may find the following resources about PHEX helpful.

  • Educational resources - Information pages

    • Endocrinology: An Integrated Approach (2001): Vitamin D resistance and rickets (http://www.ncbi.nlm.nih.gov/books/NBK24/)
    • Merck Manual Home Edition for Patients and Caregivers: Phosphate (http://www.merckmanuals.com/home/hormonal_and_metabolic_disorders/electrolyte_balance/phosphate.html)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK83985/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for PHEX (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5251%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(PHEX%5BTIAB%5D)%20OR%20((PEX%5BTIAB%5D)%20AND%20(rickets%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/300550)

  • Research Resources - Tools for researchers

    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5251)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=5251)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=8918)
    • PHEXdb: PHEX Mutation Database (http://www.phexdb.mcgill.ca/)

What other names do people use for the PHEX gene or gene products?

  • HPDR
  • HPDR1
  • HYP
  • HYP1
  • metalloendopeptidase homolog PEX
  • PEX
  • PHEX_HUMAN
  • phosphate-regulating neutral endopeptidase
  • vitamin D-resistant hypophosphatemic rickets protein
  • XLH
  • X-linked hypophosphatemia protein

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PHEX?

enzyme ; excrete ; fibroblast ; gene ; growth factor ; mineral ; phosphate ; protein ; proximal ; renal ; rickets

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet. 1995 Oct;11(2):130-6. (http://www.ncbi.nlm.nih.gov/pubmed/7550339?dopt=Abstract)
  • Clausmeyer S, Hesse V, Clemens PC, Engelbach M, Kreuzer M, Becker-Rose P, Spital H, Schulze E, Raue F. Mutational analysis of the PHEX gene: novel point mutations and detection of large deletions by MLPA in patients with X-linked hypophosphatemic rickets. Calcif Tissue Int. 2009 Sep;85(3):211-20. doi: 10.1007/s00223-009-9260-8. Epub 2009 Jun 10. (http://www.ncbi.nlm.nih.gov/pubmed/19513579?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5251)
  • Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabédian M, Jehan F. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets. Hum Genet. 2009 May;125(4):401-11. doi: 10.1007/s00439-009-0631-z. Epub 2009 Feb 15. (http://www.ncbi.nlm.nih.gov/pubmed/19219621?dopt=Abstract)
  • Ichikawa S, Traxler EA, Estwick SA, Curry LR, Johnson ML, Sorenson AH, Imel EA, Econs MJ. Mutational survey of the PHEX gene in patients with X-linked hypophosphatemic rickets. Bone. 2008 Oct;43(4):663-6. doi: 10.1016/j.bone.2008.06.002. Epub 2008 Jun 18. (http://www.ncbi.nlm.nih.gov/pubmed/18625346?dopt=Abstract)
  • Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E1-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12791601?dopt=Abstract)
  • Rowe PS. The role of the PHEX gene (PEX) in families with X-linked hypophosphataemic rickets. Curr Opin Nephrol Hypertens. 1998 Jul;7(4):367-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9690034?dopt=Abstract)
  • Rowe PS. The wrickkened pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med. 2004 Sep 1;15(5):264-81. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15470265?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2010
Published: May 20, 2013