Affinage

PRPS1

Ribose-phosphate pyrophosphokinase 1 · UniProt P60891

Length
318 aa
Mass
34.8 kDa
Annotated
2026-04-28
69 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRPS1 encodes phosphoribosyl pyrophosphate synthetase 1, the rate-limiting enzyme that converts ribose-5-phosphate to PRPP, the universal precursor for de novo and salvage synthesis of purine, pyrimidine, and NAD+ nucleotides, thereby coupling nucleotide supply to cell proliferation, DNA replication, and tissue maintenance. The enzyme is allosterically inhibited by ADP and GDP at two distinct sites, and gain-of-function mutations that disrupt this feedback cause enzyme superactivity with uric acid overproduction and thiopurine resistance in relapsed ALL, while loss-of-function mutations cause Arts syndrome, CMTX5 neuropathy, and X-linked nonsyndromic deafness (DFN2) (PMID:8253776, PMID:25962120, PMID:17701896, PMID:17701900, PMID:20021999). PRPS1 assembles into filaments in both active and inhibited conformations; filament interfaces stabilize the phosphate-binding site to enhance catalytic activity, and disease-associated mutations alter filament assembly (PMID:36747094). Activity is further tuned by CDK1 phosphorylation at S103 during S phase to fuel DNA replication, by AMPK-mediated inhibitory phosphorylation linking energy status to nucleotide output, and by CLOCK-mediated K29 acetylation that protects PRPS1 from HSC70-dependent degradation (PMID:31253668, PMID:40404919, PMID:40682742).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 Medium

    Defining the transcriptional architecture of PRPS1 established how its housekeeping expression is controlled, revealing a TATA-like element, CCAAT box, and Sp1 sites as functional cis-regulatory elements.

    Evidence CAT reporter assay with 2.0 kb 5'-flanking region across four cell lines, with S1 nuclease/primer extension mapping

    PMID:1314091

    Open questions at the time
    • Identity of cell-type-specific trans-acting factors beyond Sp1 not resolved
    • Chromatin context not examined
  2. 1993 High

    Identification of N113S and D182H as feedback-resistance mutations established the molecular basis for allosteric inhibition of PRPS1 by purine nucleotides, answering how the enzyme is regulated at the product level.

    Evidence Recombinant mutant PRPS1 expressed in E. coli with in vitro enzymatic assay showing loss of ADP/GDP inhibition

    PMID:8253776

    Open questions at the time
    • Structural basis of allosteric sites not yet resolved at this time
    • Whether additional residues participate in feedback not tested
  3. 1999 High

    Discovery that some PRPS1 superactivity results from accelerated transcription rather than coding mutations revealed a second disease mechanism and demonstrated that transcriptional output is rate-limiting for PRPP production.

    Evidence Northern blot, nuclear run-on, and Southern blot in patient fibroblasts/lymphoblasts

    PMID:10066814

    Open questions at the time
    • Transcription factor(s) driving increased transcription not identified
    • Epigenetic contribution not examined
  4. 2007 High

    Loss-of-function mutations were shown to cause two distinct X-linked diseases—Arts syndrome (L152P, Q133P) and CMTX5 neuropathy (E43D, M115T)—establishing that reduced PRPS1 activity impairs purine supply in neurons and immune cells.

    Evidence Enzymatic activity assays in patient erythrocytes and fibroblasts, segregation analysis in families

    PMID:17701896 PMID:17701900

    Open questions at the time
    • Cell-type-specific vulnerability (why neurons and hair cells are selectively affected) not explained
    • No animal model validation at this stage
  5. 2010 High

    Linking additional loss-of-function PRPS1 mutations to X-linked nonsyndromic deafness (DFN2) and demonstrating cochlear expression established that auditory hair cells are critically dependent on PRPS1-mediated nucleotide synthesis.

    Evidence Enzymatic assays in patient cells plus in situ hybridization of Prps1 in mouse cochlea

    PMID:20021999

    Open questions at the time
    • Whether cochlear phenotype is purine-specific or involves pyrimidine/NAD+ depletion not resolved
    • No conditional knockout in inner ear
  6. 2015 High

    Relapse-specific gain-of-function PRPS1 mutations were identified as a major mechanism of thiopurine resistance in childhood ALL, showing that loss of feedback inhibition constitutively activates de novo purine synthesis and competitively blocks thiopurine activation.

    Evidence Whole-exome sequencing of relapsed ALL, in vitro feedback inhibition assays, cell line drug resistance assays, and xenograft models

    PMID:25962120

    Open questions at the time
    • Frequency and clonal dynamics of PRPS1 mutations across ALL subtypes not fully mapped
    • Structural mechanism of how mutations alter allosteric sites not yet visualized
  7. 2015 High

    Identification of miR-124 as a direct negative regulator of PRPS1 mRNA demonstrated a post-transcriptional control layer linking metabolic reprogramming to colorectal cancer proliferation.

    Evidence Luciferase reporter target validation, siRNA/overexpression rescue, xenograft tumor model

    PMID:26248089

    Open questions at the time
    • Extent to which miR-124 regulation operates in non-malignant tissues not assessed
    • Other miRNAs targeting PRPS1 not surveyed
  8. 2016 High

    Zebrafish PRPS1 knockdown phenocopied human deafness and Arts syndrome features—smaller otic vesicles, reduced hair cells, motor neuron defects, and immune cell loss—providing the first vertebrate genetic model and linking the phenotype to prolonged cell cycle from nucleotide insufficiency.

    Evidence CRISPR/morpholino knockdown in zebrafish with confocal imaging, hair cell counting, and cell cycle analysis

    PMID:27425195

    Open questions at the time
    • Mammalian conditional knockout not yet performed
    • Contribution of pyrimidine vs. purine depletion not separated
  9. 2017 Medium

    The crystal structure of PRPS1 with the L191F superactivity mutation revealed how a single residue change disrupts both allosteric inhibitory sites, providing the first atomic-resolution explanation for feedback-resistant enzyme superactivity.

    Evidence X-ray crystal structure of human PRPS1 with mutant modeling and enzymatic confirmation

    PMID:28742244

    Open questions at the time
    • Only one superactivity mutation structurally characterized
    • Structure of full inhibited state not captured
  10. 2019 High

    CDK1-mediated phosphorylation of PRPS1 at S103 during S phase established a direct cell-cycle-dependent mechanism for upregulating nucleotide production during DNA replication, linking PRPS1 to proliferative control in colorectal cancer.

    Evidence Cell-cycle synchronization, S103A mutagenesis, enzymatic activity assays, phospho-specific antibody staining in 184 colorectal cancer tissues

    PMID:31253668

    Open questions at the time
    • Whether other CDK substrates in the PRPS complex are co-regulated not examined
    • Phosphatase responsible for S103 dephosphorylation not identified
  11. 2021 Medium

    PRPS1 knockout in pluripotent stem cells caused DNA damage and apoptosis, demonstrating that PRPS1-dependent purine biosynthesis is essential for stem cell genome integrity and survival.

    Evidence PRPS1 knockout in PSCs with UHPLC-MS metabolite profiling, apoptosis, and DNA damage assays

    PMID:33493137

    Open questions at the time
    • Whether PRPS2 can compensate in other stem cell contexts not tested
    • Downstream nucleotide species responsible for DNA damage not pinpointed
  12. 2022 Medium

    NRF2 was identified as an upstream transcriptional activator of PRPS1 in melanoma, providing a mechanism by which oxidative stress signaling rewires nucleotide metabolism to support tumor growth.

    Evidence ChIP/transcription factor binding assay, knockdown/overexpression in melanoma lines, xenograft models

    PMID:36203561

    Open questions at the time
    • Direct NRF2 binding site in PRPS1 promoter not mapped at nucleotide resolution
    • Not confirmed in non-melanoma contexts
  13. 2022 High

    PRPS2 mutations in relapsed ALL were shown to destabilize the PRPS1/2 hexamer interface and reduce nucleotide feedback inhibition, demonstrating that the hetero-oligomeric context of PRPS1 is critical for proper allosteric regulation.

    Evidence Ultra-deep sequencing, in vitro enzyme assays, ADP/GDP feedback inhibition assays, UPLC-MS/MS metabolomics, xenograft models

    PMID:36742181

    Open questions at the time
    • Stoichiometry of PRPS1:PRPS2 in normal vs. leukemic cells not determined
    • Whether PRPSAP1/AP2 modulate this phenotype not addressed
  14. 2023 High

    Cryo-EM structures of PRPS1 filaments in active and inhibited states revealed that polymerization stabilizes the phosphate-binding site and couples catalysis with product release across adjacent active sites, establishing filament assembly as a fundamental regulatory mechanism.

    Evidence Cryo-EM structure determination of filaments in multiple states with disease-variant mutagenesis

    PMID:36747094

    Open questions at the time
    • In vivo evidence for filament formation not yet obtained
    • How filament assembly/disassembly is regulated by cellular signals is unknown
  15. 2025 Medium

    AMPK-mediated inhibitory phosphorylation of PRPS1 established a direct energy-sensing mechanism that suppresses nucleotide biosynthesis under metabolic stress, linking OXPHOS status to PRPS1 output in melanoma.

    Evidence NDUFS3 knockdown/overexpression, AMPK activity assays, PRPS1 phosphorylation detection, metabolic flux analysis in melanoma cells

    PMID:40404919

    Open questions at the time
    • Specific AMPK phosphorylation site(s) on PRPS1 not mapped
    • Not confirmed in non-melanoma cell types
  16. 2025 Medium

    CLOCK-mediated K29 acetylation of PRPS1 was shown to protect it from HSC70-dependent degradation, revealing a circadian/signaling-dependent post-translational stabilization mechanism relevant to glioblastoma proliferation.

    Evidence Site-directed mutagenesis, immunoprecipitation, immunofluorescence, subcellular fractionation, shRNA silencing in GBM cells

    PMID:40682742

    Open questions at the time
    • Deacetylase(s) that reverse K29 acetylation not identified
    • Circadian oscillation of PRPS1 protein levels not directly demonstrated
  17. 2025 Medium

    PRPS1 deficiency was linked to NAD+/SIRT3/SOD2 pathway downregulation and mitochondrial dysfunction in auditory cells, providing a mechanistic explanation for hair cell vulnerability in PRPS1-associated deafness and suggesting NAD+ precursor supplementation as a rescue strategy.

    Evidence siRNA knockdown in HEI-OC1 cells with ROS/mitochondrial assays and NMN rescue; zebrafish mutant PRPS1 overexpression model

    PMID:40677922

    Open questions at the time
    • Whether NAD+ depletion or purine depletion is the primary cause of hair cell death not fully dissected
    • NMN rescue only partial; in vivo mammalian validation lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how PRPS1 filament assembly and disassembly are regulated in vivo; what determines cell-type-specific vulnerability to PRPS1 deficiency (neurons, hair cells, immune cells); and the precise stoichiometry and regulatory roles of PRPSAP1/PRPSAP2 within the native PRPS complex.
  • No in vivo evidence for filament dynamics
  • Conditional tissue-specific knockout in mammals not performed
  • Native complex stoichiometry and its regulation remain poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2 R-HSA-69306 DNA Replication 1
Partners
AMPKCDK1CLOCKHSC70NRF2PRPS2PRPSAP1PRPSAP2
Complex memberships
PRPS hexamer (PRPS1/PRPS2/PRPSAP1/PRPSAP2)PRPS1 filament

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Human PRPS1 assembles into filaments in both active and inhibited states, with conserved assembly interfaces that stabilize the binding site for the essential activator phosphate, thereby increasing enzymatic activity. Structures also revealed coupling of catalysis in one active site with product release in an adjacent site, demonstrating an additional allosteric regulatory layer provided by filament formation. Some disease-associated mutations alter filament assembly, linking filament stability to activity. Cryo-EM structure determination of active and inhibited PRPS1 filaments, combined with mutagenesis of disease variants Nature structural & molecular biology High 36747094
1993 Point mutations in PRPS1 (N113S and D182H) confer purine nucleotide feedback resistance and enzyme superactivity. Recombinant mutant PRS1 proteins expressed in E. coli reproduced the feedback-resistant phenotype seen in patient cells, establishing these specific residues as critical for allosteric inhibition by ADP/GDP. PCR sequencing of patient cDNA, RNase mapping, and expression of recombinant wild-type and mutant PRPS1 in E. coli with enzymatic assay The Journal of biological chemistry High 8253776
2007 Loss-of-function missense mutations in PRPS1 (L152P and Q133P) cause Arts syndrome by abolishing phosphoribosyl pyrophosphate synthetase 1 enzymatic activity, leading to impaired purine biosynthesis as evidenced by undetectable hypoxanthine in urine and reduced uric acid in serum. Molecular modeling in silico plus enzymatic activity assays in erythrocytes and fibroblasts from patients American journal of human genetics High 17701896
2007 Missense mutations in PRPS1 (E43D and M115T) at conserved residues cause X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) with decreased PRPS1 enzymatic activity demonstrated in patients harboring the M115T mutation. Mutation identification by sequencing, enzymatic activity assay in patient samples American journal of human genetics High 17701900
2010 Loss-of-function missense mutations in PRPS1 cause DFN2 nonsyndromic X-linked sensorineural deafness by abolishing PRPP synthetase 1 activity, confirmed by structural analysis and enzymatic activity assays in erythrocytes and fibroblasts; Prps1 is expressed in murine cochlear and vestibular hair cells and spiral ganglion postnatally. Structural analysis in silico, enzymatic activity assays in patient erythrocytes and fibroblasts, in situ hybridization in mouse cochlea American journal of human genetics High 20021999
1999 PRS superactivity in certain patients results from accelerated PRPS1 transcription (3–4-fold increase) rather than gene amplification or mRNA stabilization, and increased PRPS1 transcription is a major determinant of PRPP and purine nucleotide synthesis rates. Northern blot, slot blotting of nuclear run-offs, Southern blot in patient fibroblasts and lymphoblasts The Journal of biological chemistry High 10066814
2015 Relapse-specific gain-of-function missense mutations in PRPS1 reduce feedback inhibition by ADP/GDP (negative feedback-defective), constitutively activating de novo purine biosynthesis and competitively inhibiting thiopurine activation, thereby causing thiopurine resistance in childhood ALL. The de novo purine synthesis inhibitor lometrexol abrogates this resistance. Whole-exome sequencing of relapsed ALL samples, functional expression of PRPS1 mutants, enzymatic feedback inhibition assays, drug resistance assays in cell lines and xenograft models Nature medicine High 25962120
2019 CDK1 phosphorylates PRPS1 at serine 103 during S phase, upregulating its enzymatic activity to fuel nucleotide synthesis for DNA replication. Loss of S103 phosphorylation delays cell cycle progression and decreases colorectal cancer cell proliferation. Cell-cycle synchronization assays, site-directed mutagenesis (S103A), enzymatic activity assays, phospho-specific antibody staining in 184 colorectal cancer tissue samples Cancer research High 31253668
2015 miR-124 directly targets PRPS1 mRNA (and RPIA mRNA), reducing PRPS1 protein levels and thereby decreasing glucose consumption, ATP levels, DNA synthesis, and proliferation in colorectal cancer cells. Overexpression of PRPS1 rescues glycometabolism in miR-124-expressing cells. cDNA microarray, luciferase reporter (target validation), siRNA knockdown, lentiviral overexpression, xenograft tumor model Gastroenterology High 26248089
2018 PRPS1 feedback-defective mutations increase intracellular PRPP levels, which promote conversion of 5-FU to FUMP and FUTP, enhancing 5-FU-induced DNA damage and apoptosis in ALL cells, providing a mechanism for selective 5-FU sensitivity of PRPS1 mutant cells. Drug sensitivity assays in PRPS1 mutant vs. control ALL cell lines, PRPP level measurement, metabolite analysis of 5-FU conversion, apoptosis/DNA damage assays Journal of cellular and molecular medicine Medium 30255549
2022 PRPS2 mutations in relapsed ALL destabilize the PRPS1/2 hexamer, reducing nucleotide feedback inhibition and enhancing thiopurine resistance. The 3-amino-acid insert (V103-G104-E105) in PRPS2 causes steric clash at the hexamer interface, explaining the low baseline activity of PRPS2 relative to PRPS1. Ultra-deep sequencing, in vitro PRPS enzyme activity assay, ADP/GDP feedback inhibition assay, UPLC-MS/MS metabolite analysis, xenograft models Blood science High 36742181
2017 A gain-of-function PRPS1 mutation (L191F) affects the architecture of both allosteric inhibitory sites in the crystal structure of human PRPP synthetase, preventing allosteric feedback inhibition and causing enzyme superactivity with uric acid overproduction. Crystal structure analysis of human PRPS1 with mutant modeling, enzyme activity confirmation American journal of medical genetics. Part A Medium 28742244
2021 PRPS1 knockout causes DNA damage and apoptosis in pluripotent stem cells (PSCs), establishing PRPS1-mediated purine biosynthesis as essential for PSC survival, while PRPS2 depletion attenuates stemness and promotes differentiation. PRPS1 knockout in PSCs, UHPLC-MS metabolite analysis, apoptosis and DNA damage assays Aging Medium 33493137
2016 Knockdown of PRPS1 in zebrafish (prps1a and prps1b) results in smaller otic vesicles, reduced inner ear hair cell numbers, abnormal primary motor neuron development, and reduced leukocytes, phenocopying human deafness and Arts syndrome features; double mutants show increasingly severe phenotypes associated with prolonged cell cycle from reduced nucleotide synthesis. Zebrafish CRISPR/morpholino knockdown, confocal imaging, hair cell counting, primary motor neuron analysis, cell cycle analysis Scientific reports High 27425195
2025 PRPS1 deficiency in HEI-OC1 cells causes downregulation of the NAD+/SIRT3/SOD2 pathway, increased reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis; these defects are partially rescued by nicotinamide mononucleotide (NMN) supplementation. In zebrafish, overexpression of mutant PRPS1 (p.Cys165Tyr) leads to hair cell death and disrupted swimming behavior. siRNA knockdown in HEI-OC1 cells, ROS measurement, mitochondrial function assays, NAD+/SIRT3/SOD2 pathway analysis, zebrafish transgenic overexpression model Human mutation Medium 40677922
2025 AMPK phosphorylates PRPS1, suppressing its activity; NDUFS3-mediated promotion of OXPHOS and PPP increases ATP, inhibiting AMPK, which in turn releases PRPS1 from inhibitory phosphorylation and enhances purine nucleotide biosynthesis to drive melanoma proliferation. NDUFS3 knockdown/overexpression, AMPK activity assays, PRPS1 phosphorylation detection, metabolic flux analysis in melanoma cells Cell death and differentiation Medium 40404919
2025 EGF-activated CK2 phosphorylates the circadian protein CLOCK at S106, causing its nuclear export; cytosolic CLOCK then acetylates PRPS1 (and PRPS2) at K29, protecting them from HSC70-mediated degradation and enhancing GBM cell proliferation and migration. Site-directed mutagenesis, immunoprecipitation, immunofluorescence, subcellular fractionation, shRNA silencing, IHC in GBM specimens Journal of neuro-oncology Medium 40682742
1992 The PRPS1 promoter contains a TATA-like sequence, CCAAT box, and three Sp1 binding sites, and a 2.0 kb 5'-flanking region drives reporter gene (CAT) expression with activity correlating with endogenous PRPS1 mRNA levels across cell lines, establishing these cis-elements as functional promoter elements. CAT/promoter fusion reporter assay in four cell lines, S1 nuclease and primer extension mapping of transcription start sites Biochimica et biophysica acta Medium 1314091
2022 NRF2 functions as an upstream transcription factor of PRPS1, driving its upregulation in melanoma; increased PRPS1 promotes melanoma cell proliferation, migration, invasion, and inhibits apoptosis both in vitro and in vivo. ChIP or transcription factor binding assay (NRF2-PRPS1), knockdown/overexpression in melanoma cell lines, xenograft tumor models Frontiers in immunology Medium 36203561
2021 SAM supplementation replenishes erythrocyte purine nucleotides (adenosine and guanosine) in an Arts syndrome (PRPS1 deficiency) patient; co-therapy with SAM and nicotinamide riboside further improved T-cell survival and function, supporting the role of PRPS1 in purine and NAD+ nucleotide supply in immune cells. Clinical supplementation trial with biochemical monitoring of erythrocyte nucleotide levels and T-cell functional assays Molecular genetics and metabolism reports Medium 33532242
2024 The mammalian PRPS enzyme complex comprises three isozymes (PRPS1, PRPS2, testis-restricted PRPS3) and two non-enzymatic associated proteins (PRPSAP1, PRPSAP2) that operate together as a large molecular weight complex with heterogeneous multimeric configurations; cells lacking PRPS2, PRPSAP1, and PRPSAP2 render PRPS1 into aberrant homo-oligomeric assemblies with diminished metabolic flux and impaired proliferative capacity. Isogenic fibroblast knockout clones in combinatorial assembly states, co-immunoprecipitation, metabolic flux analysis, proliferation assays bioRxivpreprint Medium bio_10.1101_2024.10.01.616059

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nature medicine 135 25962120
2010 PRPS1 mutations: four distinct syndromes and potential treatment. American journal of human genetics 97 20380929
2007 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). American journal of human genetics 95 17701900
2010 Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. American journal of human genetics 80 20021999
2015 MicroRNA-124 reduces the pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells. Gastroenterology 76 26248089
2007 Arts syndrome is caused by loss-of-function mutations in PRPS1. American journal of human genetics 74 17701896
2015 Association of PRPS1 Mutations with Disease Phenotypes. Disease markers 51 26089585
2017 A profound computational study to prioritize the disease-causing mutations in PRPS1 gene. Metabolic brain disease 50 29047041
1989 Localization of human phosphoribosylpyrophosphate synthetase subunit I and II genes (PRPS1 and PRPS2) to different regions of the X chromosome and assignment of two PRPS1-related genes to autosomes. Somatic cell and molecular genetics 48 2536962
2014 X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation. Orphanet journal of rare diseases 47 24528855
1990 Cloning of cDNAs for human phosphoribosylpyrophosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes. Genomics 47 1962753
1999 Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. The Journal of biological chemistry 41 10066814
1993 Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. The Journal of biological chemistry 40 8253776
2014 Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders. European journal of human genetics : EJHG 36 24961627
2019 Cell-Cycle-Dependent Phosphorylation of PRPS1 Fuels Nucleotide Synthesis and Promotes Tumorigenesis. Cancer research 35 31253668
2014 Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. Orphanet journal of rare diseases 34 25491489
2016 Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases. Scientific reports 30 27425195
1996 Mapping of DFN2 to Xq22. Human molecular genetics 30 8968763
2012 Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. International journal of audiology 27 23190330
2017 Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Human mutation 26 28967191
2014 The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. European journal of human genetics : EJHG 26 25182139
2023 Human PRPS1 filaments stabilize allosteric sites to regulate activity. Nature structural & molecular biology 24 36747094
2013 Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy. Journal of clinical neurology (Seoul, Korea) 24 24285972
2012 Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I. American journal of medical genetics. Part A 23 22246954
2016 PRPS1 silencing reverses cisplatin resistance in human breast cancer cells. Biochemistry and cell biology = Biochimie et biologie cellulaire 20 28177767
1991 Complete nucleotide sequence of human phosphoribosyl pyrophosphate synthetase subunit I (PRS I) cDNA and a comparison with human and rat PRPS gene families. Journal of biochemistry 18 1650777
2020 PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review. European journal of medical genetics 17 32781272
2019 Zebrafish Model for Nonsyndromic X-Linked Sensorineural Deafness, DFNX1. Anatomical record (Hoboken, N.J. : 2007) 17 30874365
1992 Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II isoforms. Biochimica et biophysica acta 17 1314091
2021 Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency). Molecular genetics and metabolism reports 16 33532242
2018 Increase of PRPP enhances chemosensitivity of PRPS1 mutant acute lymphoblastic leukemia cells to 5-Fluorouracil. Journal of cellular and molecular medicine 14 30255549
2015 Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling. Pediatric research 14 25785835
2017 Novel PRPS1 gain-of-function mutation in a patient with congenital hyperuricemia and facial anomalies. American journal of medical genetics. Part A 13 28742244
2016 Functional characterization of a novel loss-of-function mutation of PRPS1 related to early-onset progressive nonsyndromic hearing loss in Koreans (DFNX1): Potential implications on future therapeutic intervention. The journal of gene medicine 13 27886419
2021 LncRNA DLEU1 Contributes to the Growth and Invasion of Colorectal Cancer via Targeting miR-320b/PRPS1. Frontiers in oncology 12 34113562
2020 Atypical presentation of Arts syndrome due to a novel hemizygous loss-of-function variant in the PRPS1 gene. Molecular genetics and metabolism reports 11 33294372
2021 PRPS1-mediated purine biosynthesis is critical for pluripotent stem cell survival and stemness. Aging 10 33493137
2016 Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report. Brain & development 10 27256512
2021 NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells. Journal of cellular and molecular medicine 9 34636169
2020 Molecular mechanism of c-Myc and PRPS1/2 against thiopurine resistance in Burkitt's lymphoma. Journal of cellular and molecular medicine 9 32391636
2020 SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis. Neuroreport 9 33105440
1990 Structure of the rat PRPS1 gene encoding phosphoribosylpyrophosphate synthetase subunit I. The Journal of biological chemistry 9 2154494
2022 Circular RNA circKIF2A Contributes to the Progression of Neuroblastoma Through Regulating PRPS1 Expression by Sponging miR-377-3p. Biochemical genetics 8 35039981
2022 Towards Understanding PRPS1 as a Molecular Player in Immune Response in Yellow Drum (Nibea albiflora). International journal of molecular sciences 8 35742917
2019 New PRPS1 variant p.(Met68Leu) located in the dimerization area identified in a French CMTX5 patient. Molecular genetics & genomic medicine 8 31338985
2019 A novel mutation in PRPS1 causes X-linked Charcot-Marie-Tooth disease-5. Neuropathology : official journal of the Japanese Society of Neuropathology 8 31434166
2022 NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma. Frontiers in immunology 7 36203561
2022 PRPS2 mutations drive acute lymphoblastic leukemia relapse through influencing PRPS1/2 hexamer stability. Blood science (Baltimore, Md.) 7 36742181
2020 KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 7 32928708
2019 A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature. Clinical rheumatology 7 31773495
2012 Ribose-phosphate pyrophosphokinase 1 (PRPS1) associated with deltamethrin resistance in Culex pipiens pallens. Parasitology research 6 23250545
2025 NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma. Cell death and differentiation 5 40404919
2021 A Novel PRPS1 Mutation in a Japanese Patient with CMTX5. Internal medicine (Tokyo, Japan) 4 34803094
2010 Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism. Nucleosides, nucleotides & nucleic acids 4 20544509
1994 Linkage of phosphoribosylpyrophosphate synthetases 1 and 2, Prps1 and Prps2, on the mouse X chromosome. Mammalian genome : official journal of the International Mammalian Genome Society 4 7849396
2024 PRPS1-associated retinopathy: a diagnostic odyssey. Ophthalmic genetics 3 38619019
2023 CRISPR/Cas9-Mediated Induction of Relapse-Specific NT5C2 and PRPS1 Mutations Confers Thiopurine Resistance as a Relapsed Lymphoid Leukemia Model. Molecular pharmacology 3 36669880
2011 Molecular analysis of X-linked inborn errors of purine metabolism: HPRT1 and PRPS1 mutations. Nucleosides, nucleotides & nucleic acids 3 22132986
2025 Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) associated retinal degeneration: an international study. Ophthalmic genetics 2 39763288
2025 SHMT, SHMTML and PRPS1 synergize to regulate blood digestion and nutrient metabolism in Aedes aegypti mosquitoes. International journal of biological macromolecules 1 40245636
2025 Generation and Auditory Phenotypic Characterization of Prps1 p.Ala87Thr Mouse Knock-In Model for Human DFNX1 Deafness. Clinical genetics 1 40494824
2025 CLOCK promotes proliferation of glioblastoma cells through acetylating PRPS1/2. Journal of neuro-oncology 1 40682742
2024 Case report on a de novo variant in the X-linked PRPS1 gene presenting with retinal dystrophy, severe tremors, and ataxia in a female patient. Ophthalmic genetics 1 39148443
2022 Experimental Clarification of PRPS-1 Structural Essentials. Cell biochemistry and biophysics 1 36201097
2015 Thiopurine Resistance in Childhood ALL Is Mediated by PRPS1 Mutations. Cancer discovery 1 25998402
2026 In silico identification of deleterious NT5C2 and PRPS1 mutations driving thiopurine resistance in relapsed acute lymphoblastic leukemia. Cancer genetics 0 41518974
2026 PRPS1 (p.V42L) Mutation in Arts Syndrome Induces Aberrant Neural Stem Cell Development and Neuronal Senescence-Like Phenotype: Rescue by Nicotinamide Mononucleotide Supplementation. International journal of stem cells 0 41787648
2025 Identification and Functional Characterization of a Novel PRPS1 Variant in X-Linked Nonsyndromic Hearing Loss: Insights From Zebrafish and Cellular Models. Human mutation 0 40677922
2017 [PRPS1 Expression in Children with Acute Leukemia and Its Clinical Significance]. Zhongguo shi yan xue ye xue za zhi 0 28446267