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PRPS1 gene
URL of this page: https://medlineplus.gov/genetics/gene/prps1/

PRPS1 gene

phosphoribosyl pyrophosphate synthetase 1

Normal Function

The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce phosphoribosyl pyrophosphate (PRPP). PRPP is needed for the first step of making molecules called nucleotides. Nucleotides are the building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. Nucleotides are categorized into two groups: purines and pyrimidines.

Purines and pyrimidines can be made from smaller molecules, or they can be recycled from the breakdown of DNA and RNA in a series of reactions called the salvage pathway. Recycling purines and pyrimidines is much more energy-efficient than making new ones, so the salvage pathway ensures that cells have a plentiful supply of purines and pyrimidines.

PRPP synthetase 1 and PRPP are involved in making new purines and pyrimidines and are also essential for the purine salvage pathway.

Health Conditions Related to Genetic Changes

Arts syndrome

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the PRPS1 gene have been found to cause Arts syndrome, a disorder that causes serious neurological problems in boys and men. Girls and women can also be affected by this condition, but they typically have milder symptoms.

The pathogenic variants in the PRPS1 gene that cause Arts syndrome change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The variants likely cause cells to produce an unstable version of the enzyme with little or no activity. The lack of functional PRPP synthetase 1 enzyme disrupts the pathway that makes new purines, the pathway that makes new pyrimidines, and the purine salvage pathway. The pyrimidine salvage pathway is not affected by these variants.

The disruption of purine production, and to a lesser extent pyrimidine production, may impair energy storage and transport in cells. This may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems that are characteristic of Arts syndrome.

More About This Health Condition

Phosphoribosylpyrophosphate synthetase superactivity

Pathogenic variants in the PRPS1 gene cause phosphoribosylpyrophosphate synthetase (PRS) superactivity. PRS superactivity is characterized by a build up of uric acid, which is caused by the breakdown of purines. The excess uric acid can cause kidney stones; bladder stones; and gout, which is a form of arthritis resulting from uric acid crystals in the joints. Some affected individuals also experience neurological problems, such as developmental delays and hearing loss. These individuals have severe PRS superactivity. 

In people with severe PRS superactivity, the condition is caused by pathogenic variants in the PRPS1 gene that change single amino acids in the PRPP synthetase 1 enzyme. These variants are called “gain-of-function variants” because they result in an overactive enzyme that cannot be turned off.  

In the milder form of PRS superactivity, the PRPS1 gene is overactive for reasons that are not well understood. PRPS1 gene overactivity increases the production of normal PRPP synthetase 1 enzyme.  

In both forms of the disorder, the increased PRPP synthetase enzyme activity leads to increased PRPP production, which causes the cell to make too many purines. When these excess purines are broken down, uric acid is produced and builds up in the body, causing many of the signs and symptoms of PRS superactivity.  

It is unclear how pathogenic variants in the PRPS1 gene are related to the neurological problems that are associated with severe PRS superactivity. It could be that the abnormal version of the enzyme is more likely to get broken down in cells that are less tolerant of change, such as nerve cells, causing these cells to produce fewer nucleotides.

More About This Health Condition

Charcot-Marie-Tooth disease

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease

More About This Health Condition

Nonsyndromic hearing loss

MedlinePlus Genetics provides information about Nonsyndromic hearing loss

More About This Health Condition

Other Names for This Gene

  • CMTX5
  • DFN2
  • DFNX1
  • PPRibP
  • PRSI

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

  • Almoguera B, He S, Corton M, Fernandez-San Jose P, Blanco-Kelly F, Lopez-Molina MI, Garcia-Sandoval B, Del Val J, Guo Y, Tian L, Liu X, Guan L, Torres RJ, Puig JG, Hakonarson H, Xu X, Keating B, Ayuso C. Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. Orphanet J Rare Dis. 2014 Dec 10;9:190. doi: 10.1186/s13023-014-0190-9. Citation on PubMed
  • Braid T, Scholten S, Yoganathan S, Alsalamah AK, Deschenes D, Deslongchamps G, Goobie S, Heon E, Tein I, Deshwar AR. Broadening the phenotypic and molecular spectrum of PRS deficiency in females. HGG Adv. 2026 Jul 9;7(3):100601. doi: 10.1016/j.xhgg.2026.100601. Epub 2026 Apr 1. Citation on PubMed
  • Camici M, Garcia-Gil M, Allegrini S, Pesi R, Bernardini G, Micheli V, Tozzi MG. Inborn Errors of Purine Salvage and Catabolism. Metabolites. 2023 Jun 24;13(7):787. doi: 10.3390/metabo13070787. Citation on PubMed
  • de Brouwer AP, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J. PRPS1 mutations: four distinct syndromes and potential treatment. Am J Hum Genet. 2010 Apr 9;86(4):506-18. doi: 10.1016/j.ajhg.2010.02.024. Citation on PubMed or Free article on PubMed Central
  • de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Petersen M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet. 2007 Sep;81(3):507-18. doi: 10.1086/520706. Epub 2007 Aug 3. Citation on PubMed or Free article on PubMed Central
  • de Brouwer APM, Christodoulou J. Phosphoribosylpyrophosphate Synthetase Deficiency. 2008 Oct 21 [updated 2023 Jun 8]. 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/NBK2591/ Citation on PubMed
  • de Brouwer APM, Christodoulou J. Phosphoribosylpyrophosphate Synthetase Superactivity. 2008 Sep 23 [updated 2022 Feb 17]. 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/NBK1973/ Citation on PubMed
  • Kim HJ, Sohn KM, Shy ME, Krajewski KM, Hwang M, Park JH, Jang SY, Won HH, Choi BO, Hong SH, Kim BJ, Suh YL, Ki CS, Lee SY, Kim SH, Kim JW. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet. 2007 Sep;81(3):552-8. doi: 10.1086/519529. Epub 2007 Jun 29. Citation on PubMed or Free article on PubMed Central
  • Liu XZ, Xie D, Yuan HJ, de Brouwer AP, Christodoulou J, Yan D. Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. Int J Audiol. 2013 Jan;52(1):23-8. doi: 10.3109/14992027.2012.736032. Epub 2012 Nov 28. Citation on PubMed or Free article on PubMed Central
  • Mittal R, Patel K, Mittal J, Chan B, Yan D, Grati M, Liu XZ. Association of PRPS1 Mutations with Disease Phenotypes. Dis Markers. 2015;2015:127013. doi: 10.1155/2015/127013. Epub 2015 May 24. Citation on PubMed or Free article on PubMed Central
  • Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. doi: 10.1016/j.ymgme.2005.07.027. Citation on PubMed
  • Zheng M, Ma JW. Research progress in the genetics of hyperuricaemia and gout. Yi Chuan. 2016 Apr;38(4):300-13. doi: 10.16288/j.yczz.15-385. Citation on PubMed

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