PRPS2 (Phosphoribosyl Pyrophosphate Synthetase 2)
A key enzyme in nucleotide biosynthesis and its role in cancer and metabolic disorders
Gene Information Card
| Symbol | PRPS2 |
|---|---|
| Full Name | Phosphoribosyl Pyrophosphate Synthetase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 5634 ncbi.nlm.nih.gov/gene/5634 |
| Ensembl ID | ENSG00000101911 |
| UniProt ID | P11908 |
| OMIM ID | 311860 |
| HGNC ID | 9463 |
| Aliases | PRSII, PRPS2 |
Description
PRPS2 encodes phosphoribosyl pyrophosphate synthetase 2, an enzyme that catalyzes the synthesis of phosphoribosyl pyrophosphate (PRPP) from ATP and ribose-5-phosphate. PRPP is a key precursor for the de novo synthesis of purine and pyrimidine nucleotides, as well as for the salvage pathways. PRPS2 is one of three isoforms (PRPS1, PRPS2, PRPS1L1) and is highly expressed in proliferating cells, including cancer cells, where it supports increased nucleotide demand. Mutations in PRPS2 are associated with X-linked Charcot-Marie-Tooth disease and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked Charcot-Marie-Tooth disease (CMTX5) | Loss-of-function mutations in PRPS2 impair PRPP synthesis, leading to peripheral neuropathy | OMIM #311860; PMID: 25217958 |
| Hereditary sensory neuropathy with deafness and cognitive impairment | PRPS2 missense variants reduce enzyme activity, affecting nucleotide metabolism in neurons | ClinVar; PMID: 25217958 |
| Cancer (multiple types) | PRPS2 overexpression and gain-of-function mutations increase PRPP levels, promoting nucleotide synthesis and tumor growth | COSMIC; PMID: 25691811 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Brain | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 4.2 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.2 | High expression |
| A549 (lung carcinoma) | 10.1 | Medium expression |
| MCF7 (breast carcinoma) | 7.5 | Medium expression |
| K562 (leukemia) | 9.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.365A>G (p.Asn122Ser) | Missense | Rare | Reduced enzyme activity; associated with CMTX5 |
| c.494C>T (p.Thr165Met) | Missense | Rare | Loss of function; linked to hereditary sensory neuropathy |
| c.104G>A (p.Arg35Gln) | Missense | Somatic (cancer) | Gain of function; increased PRPP synthesis in tumors |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Asn122Ser, p.Thr165Met) reduce PRPS2 catalytic activity, leading to nucleotide deficiency and neurological phenotypes.
Gain of Function (GOF)
Somatic mutations (e.g., p.Arg35Gln) enhance PRPS2 activity, increasing PRPP levels and supporting cancer cell proliferation.
Dominant Negative (DN)
No dominant-negative mutations have been reported for PRPS2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pentose phosphate pathway (non-oxidative branch)
• Purine metabolism (KEGG: hsa00230)
• Pyrimidine metabolism (KEGG: hsa00240)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
PRPS2 is a 318-amino acid protein that forms a homodimer or heterodimer with PRPS1. It catalyzes the rate-limiting step in PRPP synthesis, which is essential for nucleotide biosynthesis. The enzyme is allosterically regulated by ADP and GDP (inhibitors) and requires magnesium ions for activity. PRPS2 is highly expressed in testis and brain, and its overexpression is observed in various cancers, where it supports rapid cell division. Structural studies show that the active site binds ATP and ribose-5-phosphate, and mutations affecting this region impair catalysis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRPS2 Knockout HEK293 Cell Line | EDJ-KQ5548 | Human | 5634 | Details Get a Quote |
| PRPS2 Knockout A-549 Cell Line | EDJ-KQ28807 | Human | 5634 | Details Get a Quote |
| PRPS2 Knockout HCT 116 Cell Line | EDJ-KQ28808 | Human | 5634 | Details Get a Quote |
| PRPS2 Knockout HeLa Cell Line | EDJ-KQ28809 | Human | 5634 | Details Get a Quote |
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