FOLH1 (Folate Hydrolase 1)
Also known as Glutamate Carboxypeptidase II (GCPII) or Prostate-Specific Membrane Antigen (PSMA)
Gene Information Card
| Symbol | FOLH1 |
|---|---|
| Full Name | Folate Hydrolase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p11.12 |
| NCBI Gene ID | 2346 ncbi.nlm.nih.gov/gene/2346 |
| Ensembl ID | ENSG00000086205 |
| UniProt ID | Q04609 |
| OMIM ID | 600934 |
| HGNC ID | 3788 |
| Aliases | PSMA, GCPII, NAALAD1, FGCP, GCP2, mGCP |
Description
FOLH1 encodes a type II transmembrane glycoprotein with dual enzymatic activities: folate hydrolase (converting dietary folates to absorbable forms) and N-acetylated-alpha-linked acidic dipeptidase (NAALADase) activity, cleaving N-acetylaspartylglutamate (NAAG) to N-acetylaspartate (NAA) and glutamate. The protein is highly expressed in prostate epithelium and is a well-established biomarker and therapeutic target for prostate cancer (PSMA).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Overexpression of FOLH1 (PSMA) on malignant prostate cells; used for imaging (PET) and targeted therapy (e.g., 177Lu-PSMA-617). | Strong: multiple clinical trials and FDA-approved imaging agents. |
| Neuropsychiatric disorders (e.g., schizophrenia) | Altered NAALADase activity affects glutamate signaling via mGluR3 receptors. | Moderate: genetic association studies and animal models. |
| Folate malabsorption | Loss of folate hydrolase activity impairs dietary folate absorption. | Weak: rare case reports; functional studies in vitro. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | High (nTPM ~200) | High |
| Kidney | Moderate (nTPM ~30) | Medium |
| Small intestine | Moderate (nTPM ~25) | Medium |
| Brain | Low (nTPM ~5) | Low |
| Liver | Low (nTPM ~2) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | High | Androgen-sensitive; high PSMA expression |
| PC-3 (prostate cancer) | Low | Androgen-independent; low PSMA |
| 22Rv1 (prostate cancer) | Moderate | Androgen-responsive; intermediate PSMA |
| HEK293 (embryonic kidney) | Low | Minimal endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1561C>T (p.His521Tyr) | Missense | Rare (<0.01%) | Reduced NAALADase activity in vitro |
| c.1129G>A (p.Gly377Ser) | Missense | Rare (<0.01%) | Altered substrate specificity |
| c.1942C>T (p.Arg648Trp) | Missense | Rare (<0.01%) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.His521Tyr reduces NAALADase activity.
Gain of Function (GOF)
None reported.
Dominant Negative (DN)
None reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004175 - endopeptidase activity | • GO:0008233 - peptidase activity |
| • GO:0016787 - hydrolase activity | • GO:0005886 - plasma membrane |
| • GO:0042622 - photoreceptor outer segment membrane | • GO:0006508 - proteolysis |
| • GO:0006541 - glutamine metabolic process |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• NAAG metabolism (Reactome: R-HSA-8849932)
• PSMA-targeted therapy pathway (custom)
Protein Summary
FOLH1 (PSMA) is a 750-amino-acid type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain, a transmembrane helix, and a large extracellular domain containing the catalytic site. It exists as a homodimer and is heavily glycosylated. The protein has two enzymatic activities: folate hydrolase (cleaving polyglutamated folates) and NAALADase (hydrolyzing NAAG to NAA and glutamate). In prostate cancer, PSMA is upregulated and internalizes upon ligand binding, making it an ideal target for imaging and radioligand therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOLH1 Knockout HEK293 Cell Line | EDC90275 | Human | 2346 | Details Get a Quote |
| FOLH1 Knockout HeLa Cell Line | EDJ-KQ53259 | Human | 2346 | Details Get a Quote |
| FOLH1 Knockout A-549 Cell Line | EDJ-KQ61742 | Human | 2346 | Details Get a Quote |
| FOLH1 Knockout HCT 116 Cell Line | EDJ-KQ70228 | Human | 2346 | Details Get a Quote |
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