|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
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.
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.
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.
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.
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.
Cytogenetic Location: Xq21.32-q24
Molecular Location on the X chromosome: base pairs 106,871,653 to 106,894,255
The PRPS1 gene is located on the long (q) arm of the X chromosome between positions 21.32 and 24.
More precisely, the PRPS1 gene is located from base pair 106,871,653 to base pair 106,894,255 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.
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.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; arthritis ; ataxia ; ATP ; 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).
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.