Health Topics

Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( Lock Locked padlock icon ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

You Are Here:
Home →
Genetics →
Genes →
PHEX gene
URL of this page: https://medlineplus.gov/genetics/gene/phex/

PHEX gene

phosphate regulating endopeptidase X-linked

Normal Function

The PHEX gene provides instructions for making the PHEX enzyme, which appears to be important for the proper development of the bones and teeth.

Studies suggest that the PHEX enzyme affects the activity of fibroblast growth factor 23, which is a protein that helps regulate phosphate levels within the body. Phosphate is a mineral that plays a critical role in the formation and growth of bones during childhood and helps maintain bone strength in adults. Fibroblast growth factor 23 works within the intestines and the kidneys to keep the body’s phosphate levels in balance.

The PHEX enzyme may also be involved in the process that deposits minerals into developing bones and teeth (mineralization). Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding. The PHEX enzyme may interact with molecules that play a key role in regulating bone mineralization.

Researchers are working to learn more about the various functions of the PHEX enzyme and its interaction with fibroblast growth factor 23.

Health Conditions Related to Genetic Changes

X-linked hypophosphatemia

Hundreds of variants (also called mutations) in the PHEX gene have been found to cause X-linked hypophosphatemia.  This condition is characterized by low levels of phosphate in the blood (hypophosphatemia), which can lead to skeletal abnormalities. The signs and symptoms of  X-linked hypophosphatemia can include weakening or softening of the bones in growing children (rickets) or adults (osteomalacia).

Through a poorly understood mechanism, the variants in the PHEX gene that cause X-linked hypophosphatemia lead to an increase in the amount of fibroblast growth factor 23. The intestines normally absorb phosphate from food into the bloodstream, while the kidneys release excess phosphate in the urine. When more phosphate is needed, the kidneys can also reabsorb phosphate into the bloodstream.

When PHEX gene variants increase the amount of fibroblast growth factor 23, the absorption of phosphate by the intestines and the reabsorption of phosphate by the kidneys are impaired. As a result, less phosphate is available for normal bone development and maintenance, which contributes to the skeletal abnormalities seen in people with X-linked hypophosphatemia.

The PHEX gene variants that cause X-linked hypophosphatemia may also cause cells to produce an altered version of the enzyme that cannot properly interact with the molecules that are involved in bone mineralization. These changes likely also contribute to the skeletal abnormalities seen in people with X-linked hypophosphatemia.

More About This Health Condition

Other Names for This Gene

  • HPDR
  • HPDR1
  • HYP
  • HYP1
  • PEX
  • phosphate regulating endopeptidase homolog, X-linked

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Beck-Nielsen SS, Mughal Z, Haffner D, Nilsson O, Levtchenko E, Ariceta G, de Lucas Collantes C, Schnabel D, Jandhyala R, Makitie O. FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis. 2019 Feb 26;14(1):58. doi: 10.1186/s13023-019-1014-8. Citation on PubMed
  • Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabedian 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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • Kamenicky P, Briot K, Munns CF, Linglart A. X-linked hypophosphataemia. Lancet. 2024 Aug 31;404(10455):887-901. doi: 10.1016/S0140-6736(24)01305-9. Epub 2024 Aug 21. Citation on PubMed
  • Laurent MR, Harvengt P, Mortier GR, Bockenhauer D. X-Linked Hypophosphatemia. 2012 Feb 9 [updated 2023 Dec 14]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK83985/ Citation on PubMed
  • Sarafrazi S, Daugherty SC, Miller N, Boada P, Carpenter TO, Chunn L, Dill K, Econs MJ, Eisenbeis S, Imel EA, Johnson B, Kiel MJ, Krolczyk S, Ramesan P, Truty R, Sabbagh Y. Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH). Hum Mutat. 2022 Feb;43(2):143-157. doi: 10.1002/humu.24296. Epub 2021 Dec 5. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.