PFAS Gene - Phosphoribosylformylglycinamidine Synthase
Essential enzyme in de novo purine biosynthesis and potential cancer target
Gene Information Card
| Symbol | PFAS |
|---|---|
| Full Name | phosphoribosylformylglycinamidine synthase |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 5198 ncbi.nlm.nih.gov/gene/5198 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | O15067 |
| OMIM ID | 172440 |
| HGNC ID | 8863 |
| Aliases | FGAMS, GART, PRFGS |
Description
The PFAS gene encodes phosphoribosylformylglycinamidine synthase (FGAM synthase), a key enzyme in the de novo purine biosynthesis pathway. This enzyme catalyzes the conversion of formylglycinamide ribonucleotide (FGAR) to formylglycinamidine ribonucleotide (FGAM) using glutamine as a nitrogen source. PFAS is essential for cell proliferation and is frequently upregulated in various cancers, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Overexpression of PFAS supports increased purine synthesis required for rapid cell division in tumors. | COSMIC, literature |
| Acute myeloid leukemia | PFAS is overexpressed and associated with poor prognosis; inhibition reduces leukemia cell viability. | COSMIC, literature |
| Colorectal cancer | PFAS upregulation correlates with tumor progression and metabolic reprogramming. | COSMIC, literature |
| Breast cancer | High PFAS expression linked to aggressive subtypes and worse survival outcomes. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Testis | 9.8 | Medium |
| Lung | 7.1 | Low |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HepG2 (liver) | 12.1 | High expression |
| A549 (lung) | 8.9 | Medium expression |
| MCF7 (breast) | 7.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.567G>A (p.Gly189Ser) | Missense | <0.01% | Unknown; rare variant |
| c.2345_2346insA | Frameshift | <0.01% | Predicted loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of function, but no confirmed pathogenic loss-of-function variants are reported in ClinVar.
Gain of Function (GOF)
No gain-of-function mutations have been described for PFAS.
Dominant Negative (DN)
No dominant-negative mutations have been reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• De novo purine biosynthesis (Reactome: R-HSA-73817)
• Metabolism of nucleotides (Reactome: R-HSA-15869)
Protein Summary
Phosphoribosylformylglycinamidine synthase (PFAS) is a 1338-amino acid protein that functions as a homotetramer. It contains an N-terminal glutaminase domain that hydrolyzes glutamine to provide ammonia for the amidotransferase reaction. The C-terminal domain catalyzes the ATP-dependent conversion of FGAR to FGAM. PFAS is essential for purine nucleotide synthesis and is a target for anticancer drug development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
