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PHEX gene

The PHEX gene, named to signify Phosphate regulating gene with Homologies to Endopeptidases located on the X chromosome, was identified in 1995 as the gene disrupted in X-Linked Hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets (1).
XLH is inherited in an X-Linked dominant pattern and shows complete penetrance in both males and females (2, 3). Patients experience lifelong symptoms resulting from chronic hypophosphatemia including impaired bone mineralization, rickets, skeletal deformities, growth retardation and diminished quality of life (4-6).

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PHEX gene on chromosome X (11). Click to see more details.


The PHEX gene has 22 exons spanning ~220kb and encodes a 749 amino acid protein with homology to M13 zinc metallopeptidases (1). Inv arious in vitro assays, the PHEX protein has been shown to cleave putative target proteins at ASARM peptide motifs, but the physiological protein targets for PHEX cleavage are not known (7, 8).

PHEX is primarily expressed in bone and teeth where it is thought to promote mineralization by indirectly regulating the expression of the phosphate regulating hormone fibroblast growth factor 23 (FGF23) (9). PHEX is also proposed to play a role in bone and tooth mineralization that is independent of FGF23/phosphate regulation, possibly through the bone matrix protein Osteopontin (10).
More than 800 disease-causing variants in the PHEX gene have been identified in XLH patients and are represented in this Locus Specific Database (12). The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants. All of the variants are predicted to lead to a loss of PHEX protein function.

Largest locus specific database for PHEX gene mutation PHEX gene in charge of Phosphate regulation on the X chromosome X-Linked Hypophosphatemia Hypophosphatemia ricket XLH known to be related to PHEX mutation chronic hypophosphatemia impaired bone mineralization skeletal deformities growth retardation


  1. The HYP Consortium, A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets. Nat Genet 11, 130–136 (1995).
  2. Thakker, R. V., Bridging markers defining the map position of X linked hypophosphataemic rickets. J Med Genet 24(12), 756-60 (1987).
  3. Ruppe M. D., X-Linked Hypophosphatemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; (1993-2017).
  4. Liu, S. et al., How Fibroblast Growth Factor 23 Works. J Am Soc Nephrol 18, 1637-1647 (2007).
  5. Carpenter, T. O. et al., A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res 26, 1381-1388 (2011).
  6. Pavone, V. et al., Hypophosphatemic rickets: etiology, clinical features and treatment. European J Orthop Surg Traumatology Orthopédie Traumatologie 25, 221-6 (2014).
  7. Rowe, P. S. N. et al., The wrickkened-pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med 15:264 -281 4 (2004)
  8. Rowe, P. S. N. et al., Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway Crit Rev Eukaryot Gene Expr. 22(1):61-86. (2012)
  9. Beck-Nielsen, S. S. et al., FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis 14, 58 (2019).
  10. Barros, N. M. et al., Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. J Bone Miner Res 28, 688-699 (2013).
  12. Sarafrazi, S. et al., Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH). Hum Mutat. 43(2):143-157 (2022).


The information on this website is provided by Ultragenyx Pharmaceutical Inc. for educational purposes only. The PHEX gene database is not intended to replace advice from a healthcare professional and should not be used for diagnosing or treating a health problem or disease. The PHEX gene database is an open-source database that aims to provide high quality and timely data. While Ultragenyx attempts to confirm that the data submitted is accurate, Ultragenyx does not take responsibility for the quality or accuracy of the data in the PHEX gene database.

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