PPAT (Phosphoribosyl Pyrophosphate Amidotransferase)
Key enzyme in de novo purine biosynthesis, associated with metabolic disorders and cancer susceptibility.
Gene Information Card
| Symbol | PPAT |
|---|---|
| Full Name | Phosphoribosyl Pyrophosphate Amidotransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 5631 ncbi.nlm.nih.gov/gene/5631 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q06203 |
| OMIM ID | 172450 |
| HGNC ID | 9232 |
| Aliases | ATASE, GPAT, PRAT |
Description
PPAT encodes phosphoribosyl pyrophosphate amidotransferase, the rate-limiting enzyme in de novo purine nucleotide biosynthesis. It catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosyl-1-amine, using glutamine as a nitrogen source. This gene is essential for cell proliferation and is implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gout | Overactivity of PPAT may increase purine synthesis, leading to hyperuricemia and gout. | PMID: 10923035 |
| Colorectal Cancer | PPAT overexpression supports nucleotide synthesis in rapidly dividing tumor cells. | PMID: 26638075 |
| Breast Cancer | Amplification and overexpression of PPAT correlate with poor prognosis. | PMID: 28397828 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Small Intestine | 7.1 | Medium |
| Testis | 6.9 | Medium |
| Kidney | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| K562 | 11.8 | High expression |
| A549 | 9.5 | Medium expression |
| MCF7 | 7.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Reduced enzyme activity in vitro |
| c.325G>A (p.Gly109Arg) | Missense | <0.01% | Impaired glutamine binding |
| c.682C>T (p.Arg228Trp) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Thr34Met) reduce catalytic activity, potentially impairing purine synthesis.
Gain of Function (GOF)
Not well documented; amplification and overexpression in cancers suggest a gain-of-function role.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • amidophosphoribosyltransferase activity (GO:0004044) | • glutamine metabolic process (GO:0006541) |
| • purine nucleobase biosynthetic process (GO:0009113) | • cytoplasm (GO:0005737) |
Pathways
• De novo purine biosynthesis (Reactome: R-HSA-73817)
• Metabolism of nucleotides (KEGG: hsa00230)
Protein Summary
PPAT is a 517-amino acid protein that forms a homotetramer. It contains a glutaminase domain that hydrolyzes glutamine to glutamate and ammonia, and a PRTase domain that transfers the ammonia to PRPP. The enzyme is feedback-inhibited by purine nucleotides (AMP, GMP, IMP). Its activity is tightly regulated to balance purine supply with cellular demand.
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