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Genetics Home Reference: your guide to understanding genetic conditions
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PRPS1

Reviewed September 2009

What is the official name of the PRPS1 gene?

The official name of this gene is “phosphoribosyl pyrophosphate synthetase 1.”

PRPS1 is the gene's official symbol. The PRPS1 gene is also known by other names, listed below.

What is the normal function of the PRPS1 gene?

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.

How are changes in the PRPS1 gene related to health conditions?

Arts syndrome - caused by mutations in the PRPS1 gene

At least two PRPS1 gene mutations have been identified in people with Arts syndrome. These mutations 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 and the immune system, resulting in the neurological problems and immune dysfunction characteristic of Arts syndrome.

Charcot-Marie-Tooth disease - caused by mutations in the PRPS1 gene

At least two mutations in the PRPS1 gene cause a form of Charcot-Marie-Tooth disease called type X5, also known as Rosenberg-Chutorian syndrome. These mutations change single amino acids in the PRPP synthetase 1 enzyme. These genetic changes reduce enzyme activity, which disrupts the production of purines and, to a lesser extent, pyrimidines. A resulting impairment of energy storage and transport in cells of the nervous system may lead to the loss of sensation and weakness in the limbs (peripheral neuropathy), deafness, and vision loss associated with this disorder.

Some researchers believe that this condition is not actually a form of Charcot-Marie-Tooth disease. Instead, they classify it as a separate disorder characterized by peripheral neuropathy, deafness, and vision loss.

phosphoribosylpyrophosphate synthetase superactivity - caused by mutations in the PRPS1 gene

Approximately 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.

Where is the PRPS1 gene located?

Cytogenetic Location: Xq22.3

Molecular Location on the X chromosome: base pairs 107,628,423 to 107,651,025

The PRPS1 gene is located on the long (q) arm of the X chromosome at position 22.3.

The PRPS1 gene is located on the long (q) arm of the X chromosome at position 22.3.

More precisely, the PRPS1 gene is located from base pair 107,628,423 to base pair 107,651,025 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 PRPS1?

You and your healthcare professional may find the following resources about PRPS1 helpful.

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

What other names do people use for the PRPS1 gene or gene products?

  • ARTS
  • CMTX5
  • dJ1070B1.2 (phosphoribosyl pyrophosphate synthetase 1)
  • KIAA0967
  • PPRibP
  • PRPS1_HUMAN
  • PRSI

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 PRPS1?

acids ; arthritis ; ataxia ; ATP ; breakdown ; cell ; developmental delay ; DNA ; enzyme ; gene ; gout ; GTP ; hypotonia ; immune system ; kidney ; molecule ; muscle tone ; nervous system ; neurological ; neuropathy ; peripheral ; peripheral neuropathy ; protein ; purines ; pyrimidines ; RNA ; sensorineural ; sensorineural hearing loss ; syndrome ; uric acid

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

References

  • Ahmed M, Taylor W, Smith PR, Becker MA. Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1999 Mar 12;274(11):7482-8. (http://www.ncbi.nlm.nih.gov/pubmed/10066814?dopt=Abstract)
  • Becker MA, Smith PR, Taylor W, Mustafi R, Switzer RL. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest. 1995 Nov;96(5):2133-41. (http://www.ncbi.nlm.nih.gov/pubmed/7593598?dopt=Abstract)
  • Becker MA, Taylor W, Smith PR, Ahmed M. Overexpression of the normal phosphoribosylpyrophosphate synthetase 1 isoform underlies catalytic superactivity of human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1996 Aug 16;271(33):19894-9. (http://www.ncbi.nlm.nih.gov/pubmed/8702702?dopt=Abstract)
  • 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. Epub 2007 Aug 3. (http://www.ncbi.nlm.nih.gov/pubmed/17701896?dopt=Abstract)
  • García-Pavía P, Torres RJ, Rivero M, Ahmed M, García-Puig J, Becker MA. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis Rheum. 2003 Jul;48(7):2036-41. (http://www.ncbi.nlm.nih.gov/pubmed/12847698?dopt=Abstract)
  • Gene Review: Arts Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK2591/)
  • Gene Review: Charcot-Marie-Tooth Neuropathy X Type 5 (http://www.ncbi.nlm.nih.gov/books/NBK1876/)
  • Gene Review: Phosphoribosylpyrophosphate Synthetase Superactivity (http://www.ncbi.nlm.nih.gov/books/NBK1973/)
  • Kim HJ, Hong SH, Ki CS, Kim BJ, Shim JS, Cho SH, Park JH, Kim JW. A novel locus for X-linked recessive CMT with deafness and optic neuropathy maps to Xq21.32-q24. Neurology. 2005 Jun 14;64(11):1964-7. (http://www.ncbi.nlm.nih.gov/pubmed/15955956?dopt=Abstract)
  • 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. Epub 2007 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/17701900?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5631)
  • Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16176880?dopt=Abstract)
  • OMIM: PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE I (http://omim.org/entry/311850)

 

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 2009
Published: July 21, 2014