FOLR2 (Folate Receptor 2): A Key Player in Folate Metabolism and Immune Regulation
Explore the genomic, proteomic, and clinical significance of FOLR2, including its expression patterns, disease associations, and mutation landscape.
Gene Information Card
| Symbol | FOLR2 |
|---|---|
| Full Name | Folate receptor 2 (fetal) / Folate receptor beta |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 2350 ncbi.nlm.nih.gov/gene/2350 |
| Ensembl ID | ENSG00000165410 |
| UniProt ID | P14207 |
| OMIM ID | 136425 |
| HGNC ID | 3794 |
| Aliases | FR-B, FBP, FRbeta, folate receptor beta |
Description
FOLR2 encodes folate receptor beta, a glycosylphosphatidylinositol (GPI)-anchored protein that binds folate and reduced folic acid derivatives. It mediates cellular uptake of folate, which is essential for DNA synthesis and methylation. FOLR2 is primarily expressed on macrophages and placental trophoblasts, playing roles in immune regulation and fetal development. Its expression is also observed in certain cancers, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | FOLR2 is expressed on activated macrophages in inflamed synovium; folate-targeted therapies exploit this for drug delivery. | Expression data from synovial tissue; clinical trials with folate-conjugated drugs. |
| Cancer (e.g., ovarian, breast) | FOLR2 expression on tumor-associated macrophages may contribute to tumor immune evasion; potential for targeted therapy. | Immunohistochemistry and mRNA expression studies in tumor samples. |
| Neural Tube Defects | Folate deficiency is a risk factor; FOLR2 variants may affect folate transport, though direct evidence is limited. | Genetic association studies; functional studies on folate transport. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | High | Strong expression in trophoblasts |
| Spleen | Moderate | Expression in macrophages |
| Lung | Low | Alveolar macrophages |
| Liver | Low | Kupffer cells |
| Bone Marrow | Moderate | Myeloid lineage cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | Low | Differentiation to macrophages increases expression |
| U937 (monocyte) | Low | Similar to THP-1 |
| MCF7 (breast cancer) | Low | Expression may be induced under certain conditions |
| HeLa (cervical cancer) | Low | Not typically expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1540087 | SNP | ~5% (global) | May affect promoter activity; clinical significance unclear |
| rs651933 | SNP | ~10% (global) | Intronic variant; no known functional effect |
| c.448C>T (p.Arg150Cys) | Missense | Rare | Potential impact on folate binding; reported in ClinVar as uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FOLR2 are rare and not well characterized; they may impair folate uptake, but no definitive disease phenotype has been established.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FOLR2.
Dominant Negative (DN)
No dominant-negative effects have been described for FOLR2 mutations.
View complete mutation data：
Gene Ontology (GO)
| • folate binding | • folate transport |
| • receptor activity | • cell surface |
| • GPI-anchor | • immune response |
Pathways
• Folate metabolism
• One-carbon metabolism
• Macrophage-mediated immunity
Protein Summary
FOLR2 encodes a 255-amino acid protein with a signal peptide, a folate-binding domain, and a GPI-anchor signal. The mature protein is attached to the cell membrane via GPI, allowing folate capture and internalization. It shares homology with FOLR1 and FOLR3. FOLR2 is expressed on macrophages and placental cells, where it mediates folate uptake and may regulate immune responses. Its expression in tumor-associated macrophages suggests a role in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOLR2 Knockout HEK293 Cell Line | EDJ-KQ2977 | Human | 2350 | Details Get a Quote |
| FOLR2 Knockout HeLa Cell Line | EDJ-KQ53260 | Human | 2350 | Details Get a Quote |
| FOLR2 Knockout A-549 Cell Line | EDJ-KQ61744 | Human | 2350 | Details Get a Quote |
| FOLR2 Knockout HCT 116 Cell Line | EDJ-KQ70229 | Human | 2350 | Details Get a Quote |
| FOLR2 Overexpression HEK293 Stable Cell Line | EDC90822 | Human | 2350 | Details Get a Quote |
