FPGS
Folylpolyglutamate Synthase
Gene Information Card
| Symbol | FPGS |
|---|---|
| Full Name | Folylpolyglutamate Synthase |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 2356 ncbi.nlm.nih.gov/gene/2356 |
| Ensembl ID | ENSG00000136872 |
| UniProt ID | Q05932 |
| OMIM ID | 136510 |
| HGNC ID | 3824 |
| Aliases | FPGS, FLJ10631, MGC102966 |
Description
The FPGS gene encodes folylpolyglutamate synthase, a mitochondrial and cytoplasmic enzyme that catalyzes the addition of glutamate residues to folate and antifolate polyglutamates. This polyglutamation is essential for intracellular folate retention and for the synthesis of cofactors required for nucleotide biosynthesis, amino acid metabolism, and methylation reactions. FPGS activity is critical for cellular proliferation and is a determinant of response to antifolate chemotherapeutics such as methotrexate.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methotrexate Resistance | Reduced FPGS expression or activity leads to decreased polyglutamation of methotrexate, impairing its intracellular retention and efficacy. | ClinVar, COSMIC |
| Folate Deficiency | Loss-of-function mutations in FPGS can cause impaired folate polyglutamation, leading to cellular folate deficiency and megaloblastic anemia. | OMIM |
| Colorectal Cancer | Altered FPGS expression is associated with prognosis and response to 5-fluorouracil-based chemotherapy. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Small Intestine | 8.9 | Medium |
| Bone Marrow | 6.3 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.4 | Cervical cancer cell line |
| MCF7 | 11.2 | Breast cancer cell line |
| HepG2 | 13.8 | Hepatocellular carcinoma cell line |
| K562 | 7.5 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.452C>T (p.Pro151Leu) | Missense | Rare | Reduced enzyme activity, associated with folate deficiency |
| c.1016G>A (p.Arg339Gln) | Missense | Rare | Impaired methotrexate polyglutamation, linked to drug resistance |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function, severe folate deficiency |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish polyglutamate synthase activity, leading to folate deficiency and methotrexate resistance.
Gain of Function (GOF)
No gain-of-function mutations are currently documented in ClinVar or COSMIC.
Dominant Negative (DN)
No dominant-negative mutations have been reported for FPGS.
View complete mutation data：
Gene Ontology (GO)
| • folylpolyglutamate synthase activity (GO:0004326) | • ATP binding (GO:0005524) |
| • mitochondrion (GO:0005739) | • cytosol (GO:0005829) |
| • one-carbon metabolic process (GO:0006730) | • folic acid-containing compound metabolic process (GO:0006760) |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• Methotrexate action (KEGG: hsa00230)
• One-carbon metabolism (KEGG: hsa00670)
Protein Summary
Folylpolyglutamate synthase (FPGS) is a 587-amino acid protein that catalyzes the ATP-dependent addition of glutamate residues to folate and antifolate substrates. The enzyme exists in two isoforms: a mitochondrial form (with a leader sequence) and a cytoplasmic form. FPGS is essential for maintaining intracellular folate pools and for the synthesis of polyglutamated cofactors required for purine and thymidylate biosynthesis. Its activity is a key determinant of cellular sensitivity to antifolate drugs like methotrexate.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FPGS Knockout HEK293 Cell Line | EDJ-KQ4622 | Human | 2356 | Details Get a Quote |
| FPGS Knockout A-549 Cell Line | EDJ-KQ27293 | Human | 2356 | Details Get a Quote |
| FPGS Knockout HCT 116 Cell Line | EDJ-KQ27294 | Human | 2356 | Details Get a Quote |
| FPGS Knockout HeLa Cell Line | EDJ-KQ27295 | Human | 2356 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
