PRPS1

Chr XXLRX-linked

phosphoribosyl pyrophosphate synthetase 1

Also known as: ARTS, CMTX5, DFN2, DFNX1, PPRibP, PRS-I, PRSI

NCBI Gene: 5631 ENSG00000147224 UniProt: P60891 OMIM: 311850

The PRPS1 protein catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP), which is essential for nucleotide synthesis and purine metabolism. Mutations cause a spectrum of X-linked disorders including Arts syndrome (severe intellectual disability, sensorineural hearing loss, and ataxia), X-linked Charcot-Marie-Tooth disease type 5, X-linked deafness, and PRPS-related gout. This gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38) and follows X-linked inheritance patterns.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for purine metabolism and nucleotide biosynthesis. Defects in this gene are a cause of phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Arts syndromeMIM #301835

XLR

Charcot-Marie-Tooth disease, X-linked recessive, 5MIM #311070

XLR

Deafness, X-linked 1MIM #304500

X-linked

Gout, PRPS-relatedMIM #300661

XLR

Phosphoribosylpyrophosphate synthetase superactivityMIM #300661

XLR

Clinical highlights

Gene-disease validity (ClinGen)

phosphoribosylpyrophosphate synthetase superactivity · XLLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

Multiple*

Mechanism· G2P

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GeneReview available — PRPS1