PRPS1 Gene: Phosphoribosyl Pyrophosphate Synthetase 1
Key enzyme in nucleotide biosynthesis and purine metabolism; associated with X-linked disorders and cancer
Gene Information Card
| Symbol | PRPS1 |
|---|---|
| Full Name | phosphoribosyl pyrophosphate synthetase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq22.3 |
| NCBI Gene ID | 5631 ncbi.nlm.nih.gov/gene/5631 |
| Ensembl ID | ENSG00000147224 |
| UniProt ID | P60891 |
| OMIM ID | 311850 |
| HGNC ID | 9462 |
| Aliases | PRS-I, PRS1, CMTX5, DFN2, PRPS, PRPSA |
Description
The PRPS1 gene encodes phosphoribosyl pyrophosphate synthetase 1, an enzyme that catalyzes the synthesis of phosphoribosyl pyrophosphate (PRPP) from ATP and ribose-5-phosphate. PRPP is a key substrate for de novo purine and pyrimidine nucleotide biosynthesis, as well as for salvage pathways. Mutations in PRPS1 are associated with X-linked disorders including Arts syndrome, Charcot-Marie-Tooth disease type X5, and nonsyndromic sensorineural deafness. Gain-of-function mutations cause PRPS1 superactivity, leading to gout and uric acid overproduction. PRPS1 is also implicated in cancer cell proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arts syndrome | Loss-of-function mutations impair PRPP synthesis, leading to neurological and immune deficits | OMIM #301835 |
| Charcot-Marie-Tooth disease X-linked type 5 (CMTX5) | Missense mutations reduce enzyme activity, causing peripheral neuropathy and hearing loss | OMIM #311070 |
| Nonsyndromic sensorineural deafness (DFN2) | Specific PRPS1 mutations cause progressive hearing loss without other symptoms | OMIM #304500 |
| PRPS1 superactivity (gout susceptibility) | Gain-of-function mutations increase PRPP production, leading to uric acid overproduction and gout | OMIM #300661 |
| Leukemia and solid tumors | Overexpression or activating mutations promote nucleotide synthesis and cell proliferation | COSMIC; PMID: 25691885 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | High |
| Heart | 12.8 | High |
| Liver | 10.5 | Medium |
| Kidney | 9.1 | Medium |
| Lung | 7.3 | Medium |
| Testis | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney cells; high expression |
| K562 | 14.2 | Leukemia cell line |
| HeLa | 12.1 | Cervical cancer cells |
| HepG2 | 10.8 | Hepatocellular carcinoma |
| A549 | 9.5 | Lung adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.455A>G (p.Asn152Ser) | Missense | Rare | Reduced enzyme activity; associated with CMTX5 |
| c.640C>T (p.Arg214Cys) | Missense | Rare | Loss-of-function; Arts syndrome |
| c.115G>A (p.Gly39Arg) | Missense | Rare | Gain-of-function; PRPS1 superactivity |
| c.338G>A (p.Arg113His) | Missense | Rare | Hearing loss (DFN2) |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of function; severe Arts syndrome |
Mutation functional classification
Loss of Function (LOF)
Missense or nonsense mutations that reduce or abolish PRPS1 enzymatic activity, leading to Arts syndrome, CMTX5, or DFN2. Examples: p.Asn152Ser, p.Arg214Cys.
Gain of Function (GOF)
Missense mutations that increase PRPS1 activity, causing PRPS1 superactivity with hyperuricemia and gout. Example: p.Gly39Arg.
Dominant Negative (DN)
Not well documented for PRPS1; most pathogenic mutations are X-linked recessive or hemizygous in males.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Purine metabolism (KEGG: hsa00230)
• Pyrimidine metabolism (KEGG: hsa00240)
• Pentose phosphate pathway (KEGG: hsa00030)
• Metabolic pathways (KEGG: hsa01100)
• PRPP biosynthesis (Reactome: R-HSA-73843)
Protein Summary
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is a 318-amino acid enzyme that forms a homodimer or heterodimer with PRPS2. It catalyzes the rate-limiting step in PRPP synthesis, essential for nucleotide biosynthesis. The protein is ubiquitously expressed with highest levels in brain and heart. Structural studies show a Rossmann-like fold with a flexible loop regulating substrate binding. Post-translational modifications include phosphorylation at Ser103, which modulates activity. PRPS1 is inhibited by ADP and GDP via allosteric feedback.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRPS1 Knockout HEK293 Cell Line | EDJ-KQ2295 | Human | 5631 | Details Get a Quote |
| PRPS1L1 Knockout HEK293 Cell Line | EDJ-KQ8127 | Human | 221823 | Details Get a Quote |
| PRPS1 Knockout HCT 116 Cell Line | EDJ-KQ21331 | Human | 5631 | Details Get a Quote |
| PRPS1 Knockout A-549 Cell Line | EDJ-KQ22659 | Human | 5631 | Details Get a Quote |
| PRPS1 Knockout HeLa Cell Line | EDJ-KQ22661 | Human | 5631 | Details Get a Quote |
| PRPS1L1 Knockout HeLa Cell Line | EDJ-KQ59177 | Human | 221823 | Details Get a Quote |
| PRPS1L1 Knockout A-549 Cell Line | EDJ-KQ67648 | Human | 221823 | Details Get a Quote |
| PRPS1L1 Knockout HCT 116 Cell Line | EDJ-KQ76034 | Human | 221823 | Details Get a Quote |
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