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Orphanet References OMIM Gene GeneReviews HGMD HGNC
last update : 03-09-2019
Symbol PRPS1
Location Xq22.3
Name gout, with/without neurodevelopmental abnormalities (PRPS overexpression)
Corresponding gene PRPS1
Main clinical features
  • neurologic symptoms, including sensorineural deafness, with increased enzyme activity associated to hyperuricemia and gout
  • early-adult onset of excessive purine production, gout, and uric acid urolithiasis associated with hyperuricemia and hyperuricosuria
  • Genetic determination sex linked
    Function/system disorder metabolism/purine or pyrimidine
    Type disease
    Gene product
    Name phosphoribosyl pyrophosphate synthetase 1 (PRPS1)
    Gene mutationChromosome rearrangementEffectComments
    various types   abnormal protein/gain of function  
  • mutation involving pretranslational dysregulation of PRPS1 expression and might be more appropriately termed overactivity of normal PRPS1
  • substitution of Ser for Asn114 leads to remarkable alterations of both the ATP-binding conformation and the aggregation-dependent allosteric inhibition , resulting in an increased concentration of the product PRPP in the patient, and may finally cause gout (Liu (2009)
  • effect of the p.Val142Leu change on protein activity is determined by the cell type, being a gain-of-function in proliferating cells and a loss-of-function in postmitotic cells (PMID: 22246954))
  • missense mutations in PRPS1 can cause a continuous spectrum of features ranging from progressive non-syndromic postlingual hearing impairment to uric acid overproduction, neuropathy, and recurrent infections depending on the functional sites that are affected (PMID: 22246954))