PRPS1
Chr XXLRX-linkedphosphoribosyl pyrophosphate synthetase 1
Also known as: ARTS, CMTX5, DFN2, DFNX1, PPRibP, PRS-I, PRSI
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.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PRPS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools