Details for: PRPS1

Gene ID: 5631

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRPS1

Ensembl ID: ENSG00000147224

Description: phosphoribosyl pyrophosphate synthetase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • rod bipolar cell CL0000751
    CSI 11.39
    rCSI 20.47%
    PRS 63.99
  • vascular associated smooth muscle cell CL0000359
    CSI 6.21
    rCSI 20.13%
    PRS 70.17
  • multi-ciliated epithelial cell CL0005012
    CSI 5.61
    rCSI 5.6%
    PRS 64.43
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 5.51
    rCSI 4.19%
    PRS 83.66
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.19
    rCSI 3.35%
    PRS 87.85
  • peripheral nervous system neuron CL2000032
    CSI 3.78
    rCSI 5.15%
    PRS 62.27
  • myeloid leukocyte CL0000766
    CSI 3.77
    rCSI 3.48%
    PRS 72.73
  • cardiac neuron CL0010022
    CSI 3.76
    rCSI 12.04%
    PRS 67.98
  • erythroid progenitor cell CL0000038
    CSI 3.51
    rCSI 20.15%
    PRS 78.54
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.47
    rCSI 2.34%
    PRS 84.05
  • double negative thymocyte CL0002489
    CSI 3.37
    rCSI 2.34%
    PRS 82.39
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.14
    rCSI 2.71%
    PRS 75.67
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 2.93
    rCSI 14.69%
    PRS 83.32
  • pro-B cell CL0000826
    CSI 2.88
    rCSI 2.38%
    PRS 73.36
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.88
    rCSI 2.06%
    PRS 84.34
  • granulocyte CL0000094
    CSI 2.86
    rCSI 4.37%
    PRS 79.81
  • naive T cell CL0000898
    CSI 2.83
    rCSI 1.97%
    PRS 85.45
  • CD4-positive helper T cell CL0000492
    CSI 2.69
    rCSI 2.03%
    PRS 84.1
  • hematopoietic stem cell CL0000037
    CSI 2.67
    rCSI 1.78%
    PRS 73.78
  • pancreatic A cell CL0000171
    CSI 2.64
    rCSI 2.77%
    PRS 74.37
  • common myeloid progenitor CL0000049
    CSI 2.62
    rCSI 2.12%
    PRS 72.88
  • perivascular cell CL4033054
    CSI 2.54
    rCSI 3.47%
    PRS 76.49
  • erythroid lineage cell CL0000764
    CSI 2.53
    rCSI 16.25%
    PRS 84.41
  • early lymphoid progenitor CL0000936
    CSI 2.52
    rCSI 2.22%
    PRS 76.35
  • plasmablast CL0000980
    CSI 2.52
    rCSI 1.99%
    PRS 77.45
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.41
    rCSI 2.37%
    PRS 85.46
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 2.41
    rCSI 1.42%
    PRS 87.07
  • ionocyte CL0005006
    CSI 2.34
    rCSI 2.5%
    PRS 71.42
  • precursor B cell CL0000817
    CSI 2.33
    rCSI 2.04%
    PRS 79.44
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.33
    rCSI 2.15%
    PRS 87.87
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.31
    rCSI 4.08%
    PRS 51.16
  • neural crest cell CL0011012
    CSI 2.26
    rCSI 1.78%
    PRS 58.18
  • T follicular helper cell CL0002038
    CSI 2.25
    rCSI 1.69%
    PRS 84.91
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.23
    rCSI 2.01%
    PRS 68.23
  • pancreatic D cell CL0000173
    CSI 2.22
    rCSI 2.19%
    PRS 73.52
  • group 3 innate lymphoid cell CL0001071
    CSI 2.08
    rCSI 1.57%
    PRS 76.81
  • ciliated epithelial cell CL0000067
    CSI 2.06
    rCSI 1.81%
    PRS 59.02
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.05
    rCSI 2.09%
    PRS 82.18
  • class switched memory B cell CL0000972
    CSI 1.95
    rCSI 1.46%
    PRS 85.61
  • immature B cell CL0000816
    CSI 1.92
    rCSI 1.43%
    PRS 83.37
  • alternatively activated macrophage CL0000890
    CSI 1.91
    rCSI 2.4%
    PRS 82.02
  • choroid plexus epithelial cell CL0000706
    CSI 1.87
    rCSI 3.06%
    PRS 59.92
  • mature B cell CL0000785
    CSI 1.86
    rCSI 1.62%
    PRS 81.37
  • mesodermal cell CL0000222
    CSI 1.86
    rCSI 2.23%
    PRS 69.11
  • plasmacytoid dendritic cell, human CL0001058
    CSI 1.77
    rCSI 1.24%
    PRS 73.95
  • club cell CL0000158
    CSI 1.77
    rCSI 2.59%
    PRS 65.79
  • epithelial cell of lung CL0000082
    CSI 1.76
    rCSI 1.46%
    PRS 71.05
  • promyelocyte CL0000836
    CSI 1.75
    rCSI 2.53%
    PRS 78.78
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.68
    rCSI 2.01%
    PRS 88.03
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.68
    rCSI 1.94%
    PRS 63.27
  • inhibitory interneuron CL0000498
    CSI 1.67
    rCSI 3.85%
    PRS 58.98
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.66
    rCSI 3.78%
    PRS 66.02
  • retinal cone cell CL0000573
    CSI 1.63
    rCSI 2.62%
    PRS 60.25
  • T-helper 17 cell CL0000899
    CSI 1.6
    rCSI 1.27%
    PRS 89.77
  • radial glial cell CL0000681
    CSI 1.6
    rCSI 2.22%
    PRS 69.34
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.56
    rCSI 4.49%
    PRS 88.92
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.55
    rCSI 2.13%
    PRS 88.39
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.51
    rCSI 1.94%
    PRS 67.41
  • stem cell CL0000034
    CSI 1.5
    rCSI 1.45%
    PRS 62.67
  • mesenchymal cell CL0008019
    CSI 1.5
    rCSI 3.8%
    PRS 64.54
  • tendon cell CL0000388
    CSI 1.45
    rCSI 3.76%
    PRS 81.97
  • retina horizontal cell CL0000745
    CSI 1.37
    rCSI 2.08%
    PRS 67.31
  • keratinocyte CL0000312
    CSI 1.33
    rCSI 1.11%
    PRS 74.42
  • basal cell CL0000646
    CSI 1.3
    rCSI 1.74%
    PRS 70.66
  • type B pancreatic cell CL0000169
    CSI 1.18
    rCSI 2.6%
    PRS 69.55
  • glioblast CL0000030
    CSI 1.17
    rCSI 1.87%
    PRS 62.63
  • lung ciliated cell CL1000271
    CSI 1.05
    rCSI 1.22%
    PRS 61.97
  • erythrocyte CL0000232
    CSI 1.04
    rCSI 2.36%
    PRS 73.13
  • forebrain radial glial cell CL0013000
    CSI 1
    rCSI 3.21%
    PRS 74.43
  • germinal center B cell CL0000844
    CSI 0.82
    rCSI 2.45%
    PRS 84.28
  • large pre-B-II cell CL0000957
    CSI 0.77
    rCSI 2.21%
    PRS 79.72
  • podocyte CL0000653
    CSI 0.77
    rCSI 3.42%
    PRS 71.22
  • primitive red blood cell CL0002355
    CSI 0.68
    rCSI 3.67%
    PRS 80.27
  • cytotoxic T cell CL0000910
    CSI 0.19
    rCSI 1.09%
    PRS 77.92
  • pluripotent stem cell CL0002248
    CSI 0.16
    rCSI 4.75%
    PRS 86.26

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRPS1](/details-gene/5631), or Phosphoribosyl Pyrophosphate Synthetase 1, is a protein-coding gene located on the X chromosome that encodes a critical enzyme in nucleotide metabolism. This enzyme catalyzes the synthesis of 5-phosphoribosyl-1-pyrophosphate (PRPP), a fundamental precursor for the de novo and salvage pathways of purine and pyrimidine biosynthesis. Reflecting its central role in cellular proliferation and metabolism, [PRPS1](/details-gene/5631) is broadly expressed but shows particularly high significance in metabolically active cells, including neuronal cell types like the [rod bipolar cell](/details-cell/CL0000751) and various hematopoietic progenitors and lymphocyte populations. Mutations in [PRPS1](/details-gene/5631) are associated with a spectrum of X-linked disorders, with gain-of-function mutations causing PRPS1 superactivity (e.g., Arts syndrome, [OMIM: 301835](https://omim.org/entry/301835)) and loss-of-function mutations leading to conditions such as Charcot-Marie-Tooth disease X-linked recessive type 5 ([OMIM: 311070](https://omim.org/entry/311070)) and nonsyndromic sensorineural deafness 2 ([OMIM: 304500](https://omim.org/entry/304500)). ## Cellular Roles and Expression Landscape The expression profile of [PRPS1](/details-gene/5631) highlights its essential function in cells with high metabolic or proliferative demands. **Overall**, the gene exhibits its highest cell significance index (CSI) in [rod bipolar cell](/details-cell/CL0000751) (CSI: 11.39), a specialized retinal neuron, which may explain the optic neuropathy observed in some [PRPS1](/details-gene/5631)-related disorders ([Link](https://doi.org/10.1086/519529)). Its significance is also pronounced in other structurally and functionally diverse cells requiring high energetic turnover, such as [vascular associated smooth muscle cell](/details-cell/CL0000359) (CSI: 6.21) and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 5.61). A major functional context for [PRPS1](/details-gene/5631) is within the hematopoietic and immune systems. The gene shows high significance in various stages of lymphocyte development and differentiation, including [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810), [double negative thymocyte](/details-cell/CL0002489), and [pro-B cell](/details-cell/CL0000826). Furthermore, it is a key gene in mature effector and memory T-cell populations, such as the [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 5.51) and [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907). This pattern is consistent with the high demand for nucleotide synthesis required for the rapid clonal expansion that characterizes an adaptive immune response. The gene's importance is further underscored by its significant expression in progenitor populations like the [erythroid progenitor cell](/details-cell/CL0000038) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557), indicating a foundational role in hematopoiesis. ## Pathways and Molecular Function [PRPS1](/details-gene/5631) encodes an enzyme with [ribose phosphate diphosphokinase activity](/details-go/GO:0004749) that performs the critical [5-phosphoribose 1-diphosphate biosynthetic process](/details-go/GO:0006015), a key step in the [pentose phosphate pathway](/reactome/R-HSA-71336). This function is central to overall cellular [metabolism](/reactome/R-HSA-1430728), as PRPP is the rate-limiting substrate for both the [purine nucleotide biosynthetic process](/details-go/GO:0006164) and the [pyrimidine nucleotide biosynthetic process](/details-go/GO:0006221). Its activity is dependent on [ATP binding](/details-go/GO:0005524) and [magnesium ion binding](/details-go/GO:0000287), and the protein is known to form functional homodimers ([GO:0042803](https://www.ebi.ac.uk/QuickGO/term/GO:0042803)). The functional annotations directly align with the clinical manifestations of its dysfunction; for instance, its involvement in [nervous system development](/details-go/GO:0007399) provides a molecular basis for the neuropathy, deafness, and optic atrophy seen in patients with pathogenic variants ([Link](https://doi.org/10.1086/520706); [Link](https://doi.org/10.1086/519529)). ## Research Directions The diverse clinical phenotypes arising from mutations in [PRPS1](/details-gene/5631), combined with its specific cellular expression patterns, suggest several avenues for future research. The data highlight a dichotomy between its ubiquitous, essential housekeeping function and the highly specific tissue damage seen in associated pathologies. Based on the available data, the following hypotheses can be proposed: 1. The exceptional vulnerability of specific neuronal populations, such as [rod bipolar cells](/details-cell/CL0000751) and peripheral neurons, to [PRPS1](/details-gene/5631) dysfunction stems from a unique and sustained reliance on de novo nucleotide synthesis to maintain their high metabolic rate and complex cytoarchitecture, making them unable to compensate for even partial loss of enzyme function. 2. The severity of immunodeficiency in some [PRPS1](/details-gene/5631)-related syndromes is primarily due to a failure of lymphocyte clonal expansion during immune responses, as T and B cells are acutely dependent on PRPS1-mediated synthesis for rapid proliferation and cannot be sustained by salvage pathways alone. To test the first hypothesis regarding neuronal vulnerability, a key experiment could be conducted. One could utilize induced pluripotent stem cells (iPSCs) from patients with loss-of-function [PRPS1](/details-gene/5631) mutations and corresponding isogenic controls to generate retinal organoids. By performing single-cell RNA sequencing and metabolic flux analysis at different stages of organoid development, one could specifically assess whether developing [rod bipolar cells](/details-cell/CL0000751) exhibit unique metabolic bottlenecks, signs of ER stress, or apoptotic markers that are absent in other retinal cell types within the same culture. From a therapeutic standpoint, [PRPS1](/details-gene/5631) represents a challenging target. Its fundamental role in nucleotide synthesis means that systemic inhibition would likely lead to severe toxicity, particularly in highly proliferative tissues like the gut and bone marrow. However, in the context of certain cancers that are heavily reliant on de novo purine synthesis, targeted delivery of a [PRPS1](/details-gene/5631) inhibitor could represent a viable anti-proliferative strategy. For the X-linked loss-of-function disorders, the therapeutic approach would be activation or replacement. Gene therapy, using AAV vectors to deliver a functional copy of [PRPS1](/details-gene/5631) to specific affected tissues like the inner ear or retina, presents a potential, albeit technically challenging, long-term therapeutic avenue.

Genular Protein ID: 2135148338

Symbol: PRPS1_HUMAN

Name: PPRibP

UniProtKB Accession Codes:

P60891 B1ALA8 B2R6T7 B4DNL6 D3DUX6 P09329

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 1 EMBL 10 EMDB 17 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 9 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 6 OrthoDB 1 PANTHER 2 PDB 25 PDBsum 25 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 2 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2155397

Title: Cloning of two distinct copies of human phosphoribosylpyrophosphate synthetase cDNA.

PubMed ID: 2155397

DOI: 10.1093/nar/18.1.193

PubMed ID: 1650777

Title: Complete nucleotide sequence of human phosphoribosyl pyrophosphate synthetase subunit I (PRS I) cDNA and a comparison with human and rat PRPS gene families.

PubMed ID: 1650777

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1314091

Title: Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II isoforms.

PubMed ID: 1314091

DOI: 10.1016/0167-4781(92)90521-z

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 16939420

Title: Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site.

PubMed ID: 16939420

DOI: 10.1042/bj20061066

PubMed ID: 7593598

Title: The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity.

PubMed ID: 7593598

DOI: 10.1172/jci118267

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 17701896

Title: Arts syndrome is caused by loss-of-function mutations in PRPS1.

PubMed ID: 17701896

DOI: 10.1086/520706

PubMed ID: 17701900

Title: 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).

PubMed ID: 17701900

DOI: 10.1086/519529

PubMed ID: 20021999

Title: Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.

PubMed ID: 20021999

DOI: 10.1016/j.ajhg.2009.11.015

PubMed ID: 22246954

Title: Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I.

PubMed ID: 22246954

DOI: 10.1002/ajmg.a.34428

PubMed ID: 25491489

Title: Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy.

PubMed ID: 25491489

DOI: 10.1186/s13023-014-0190-9

Sequence Information:

  • Length: 318
  • Mass: 34834
  • Checksum: 46D017E969908BA0
  • Sequence:
    • MPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC 
GEINDNLMEL LIMINACKIA SASRVTAVIP CFPYARQDKK DKSRAPISAK LVANMLSVAG 
ADHIITMDLH ASQIQGFFDI PVDNLYAEPA VLKWIRENIS EWRNCTIVSP DAGGAKRVTS 
IADRLNVDFA LIHKERKKAN EVDRMVLVGD VKDRVAILVD DMADTCGTIC HAADKLLSAG 
ATRVYAILTH GIFSGPAISR INNACFEAVV VTNTIPQEDK MKHCSKIQVI DISMILAEAI 
RRTHNGESVS YLFSHVPL

Genular Protein ID: 1687109405

Symbol: B7ZB02_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7ZB02

Database IDs:

ARBA 4 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 8 Gene3D 1 HOGENOM 1 InterPro 3 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

Sequence Information:

  • Length: 114
  • Mass: 12324
  • Checksum: A2BA69EDAB8EF6B9
  • Sequence:
    • MVLVGDVKDR VAILVDDMAD TCGTICHAAD KLLSAGATRV YAILTHGIFS GPAISRINNA 
CFEAVVVTNT IPQEDKMKHC SKIQVIDISM ILAEAIRRTH NGESVSYLFS HVPL