### Overview of FOLR3 Gene

**Gene Symbol**: FOLR3  
**Chromosomal Location**: Chromosome 11

The FOLR3 gene encodes a protein that belongs to the folate receptor family, which plays a critical role in the cellular uptake of folate and its derivatives, particularly 5-methyltetrahydrofolate. This receptor is particularly notable for its high affinity for folate, which is essential for nucleotide synthesis and overall cellular processes.

### 1. Associated Genes

FOLR3 is part of a gene cluster with other folate receptor genes, including:

- **FOLR1**: The most studied folate receptor, associated with intracellular folate transport and cellular uptake.
- **FOLR2**: Another member of the folate receptor family, involved in the uptake of folate and implicated in cancer biology.
- **FOLR4**: A less characterized folate receptor, but still part of the folate transport mechanism.

These genes collectively participate in folate transport and metabolism, particularly in tissues where rapid cell division occurs, such as in tumors.

### 2. Aging and Age-Related Diseases

- **Cancer**: Elevated expression of FOLR3 has been observed in cancers, especially in ovarian and primary peritoneal carcinoma. This suggests that FOLR3 could be linked to the pathogenesis of certain age-related cancers.
- **Neurological Health**: Reduced levels of folate in the body have been associated with cognitive decline and the development of age-related neurodegenerative diseases, such as Alzheimer's disease. While FOLR3 is not exclusively studied in this context, its role in folate transport raises the possibility of its involvement in these diseases.

### 3. Drug Interactions

FOLR3 has potential interactions with the following drugs and drug classes:

- **Methotrexate**: An antifolate drug that inhibits dihydrofolate reductase, used in cancer therapy; its mechanism may indirectly affect FOLR3's function due to competition with folate uptake.
- **Folic Acid Supplements**: Though not a direct interaction, high doses of folic acid could influence the expression and activity of folate receptors, including FOLR3, as the cells may attempt to increase uptake mechanisms in response to elevated folate levels.
- **General Anticancer Agents**: Due to the receptor's overexpression in tumors, therapies that target folate receptors (like folate-targeted chemotherapies) may affect FOLR3.

### 4. Pathways and Biological Processes

FOLR3 is implicated in several biological processes, including:

- **Folate Transport**: FOLR3 is crucial for the transport of folate across cell membranes, making it vital for maintaining folate homeostasis in tissues.
- **Cell Proliferation**: It plays a role in supporting cell growth and division, particularly important in rapidly dividing tissues such as tumors.
- **Cellular Response to Folate**: FOLR3 is involved in mediating cellular responses to folate status, influencing metabolic pathways associated with amino acid synthesis and DNA replication.

#### Pathways:

- **Folate Biochemistry**: FOLR3 is involved in pathways that manage the uptake and metabolism of folate in the context of nucleotide synthesis.
- **Cancer Progression Pathways**: Its expression in various cancers links it to regulatory pathways that control cancer cell proliferation and survival.

In summary, FOLR3 is a significant gene that encodes a key receptor in folate metabolism, with implications in cancer biology and potential associations with aging and age-related diseases. Its interplay with pharmacologic agents and involvement in critical cellular pathways underscores its importance in both health and disease.