PRPS1 Gene: History
Please note this is an old version of this entry, which may differ significantly from the current revision.

phosphoribosyl pyrophosphate synthetase 1

  • genes

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 a molecule called phosphoribosyl pyrophosphate (PRPP). PRPP is involved in making purine and pyrimidine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.

Purines and pyrimidines may be manufactured from smaller molecules, or they can be recycled from the breakdown of DNA and RNA in a series of reactions called the salvage pathway. Manufacturing purines and pyrimidines uses much more energy and takes more time than recycling them, which makes recycling these molecules more efficient. The salvage pathway ensures that cells have a plentiful supply of purines and pyrimidines.

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

2. Health Conditions Related to Genetic Changes

2.1. Arts syndrome

At least three PRPS1 gene mutations have been identified in people with Arts syndrome, a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.

The PRPS1 gene mutations that cause Arts syndrome change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The mutations are believed to result in the production of an unstable enzyme with little or no activity. The lack of functional PRPP synthetase 1 enzyme disrupts both the manufacture and recycling of purines. The manufacture of pyrimidines is also affected, but not the pyrimidine salvage pathway. The disruption of purine production, and to a lesser extent pyrimidine production, may impair energy storage and transport in cells. Impairment of these processes 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 characteristic of Arts syndrome.

2.2. Phosphoribosylpyrophosphate synthetase superactivity

At least seven mutations in the PRPS1 gene that cause a severe form of phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) have been identified. These mutations change single amino acids in the PRPP synthetase 1 enzyme, resulting in a poorly regulated, overactive enzyme. In a 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, which increases the availability of PRPP. In both forms of the disorder, excessive amounts of purines are generated.

Under these conditions, uric acid, a waste product of purine breakdown, accumulates in the body. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. Affected individuals may also develop kidney or bladder stones formed from uric acid crystals.

People with the severe form of PRS superactivity have additional symptoms including loss of hearing caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay. It is unclear how the PRPS1 gene mutations that cause the severe form of PRS superactivity are related to these neurological problems.

3. Other Names for This Gene

  • ARTS

  • CMTX5

  • dJ1070B1.2 (phosphoribosyl pyrophosphate synthetase 1)

  • KIAA0967

  • PPRibP


  • PRSI

This entry is adapted from the peer-reviewed paper


  1. Ahmed M, Taylor W, Smith PR, Becker MA. Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. JBiol Chem. 1999 Mar 12;274(11):7482-8.
  2. Becker MA, Smith PR, Taylor W, Mustafi R, Switzer RL. The genetic andfunctional basis of purine nucleotide feedback-resistantphosphoribosylpyrophosphate synthetase superactivity. J Clin Invest. 1995Nov;96(5):2133-41.
  3. Becker MA, Taylor W, Smith PR, Ahmed M. Overexpression of the normalphosphoribosylpyrophosphate synthetase 1 isoform underlies catalyticsuperactivity of human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1996 Aug 16;271(33):19894-9.
  4. 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. Review.
  5. 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.
  6. de Brouwer APM, Christodoulou J. Arts Syndrome. 2008 Oct 21 [updated 2018 Mar 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available from
  7. de Brouwer APM, Duley JA, Christodoulou J. PhosphoribosylpyrophosphateSynthetase Superactivity. 2008 Sep 23 [updated 2015 Dec 17]. In: Adam MP,Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors.GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle;1993-2020. Available from
  8. Kim HJ, Sohn KM, Shy ME, Krajewski KM, Hwang M, Park JH, Jang SY, Won HH, ChoiBO, 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 fornucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing lossand optic neuropathy (cmtx5). Am J Hum Genet. 2007 Sep;81(3):552-8.
  9. Kim JW, Kim HJ. Charcot-Marie-Tooth Neuropathy X Type 5. 2008 Aug 26 [updated 2013 Jun 6]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, StephensK, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available from
  10. Liu XZ, Xie D, Yuan HJ, de Brouwer AP, Christodoulou J, Yan D. Hearing lossand PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. Int JAudiol. 2013 Jan;52(1):23-8. doi: 10.3109/14992027.2012.736032.Review.
  11. Mittal R, Patel K, Mittal J, Chan B, Yan D, Grati M, Liu XZ. Association ofPRPS1 Mutations with Disease Phenotypes. Dis Markers. 2015;2015:127013. doi:10.1155/2015/127013.
  12. Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005Sep-Oct;86(1-2):25-33. Review.
  13. 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. Review.
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