### EPAS1 Gene Overview:

**Gene Symbol:** EPAS1 (also known as HIF-2α)

**Function:** The EPAS1 gene encodes a transcription factor that is primarily involved in the hypoxic response, regulating gene expression in response to low oxygen levels. It forms heterodimers with the ARNT (Aryl hydrocarbon Receptor Nuclear Translocator) and binds to hypoxia response elements (HRE) on the promoters of target genes, facilitating the induction of a variety of genes that are crucial for adaptive responses to hypoxia, notably vascular endothelial growth factor (VEGF) and other angiogenic factors.

### 1. Associated Genes:
While the NCBI and UniProt summaries primarily mention ARNT and VEGF, EPAS1 is also associated with several other genes and pathways, including:

- **HIF-1α (HIF1A):** Another hypoxia-inducible factor that can also heterodimerize with ARNT.
- **EPAS1-regulated genes:** Genes involved in angiogenesis, metabolism (like glycolytic enzymes), and erythropoiesis (such as EPO, erythropoietin).
- **Members of the Tie receptor family:** Specifically, Tie-2, which is crucial for endothelial cell function.
- **Transcriptional coactivators:** Such as CREBBP and EP300 that interact with EPAS1 for enhanced transcriptional activation.

### 2. Aging and Age-Related Diseases:
EPAS1 has implications in various age-related conditions, including:

- **Age-related hypoxia:** As tissues age, their efficiency in accessing oxygen may decrease, leading to increased expression of hypoxia-responsive genes.
- **Vascular diseases:** Altered EPAS1 activity may contribute to an increased risk of cardiovascular diseases, which are exacerbated with aging due to chronic hypoxia (such as ischemic conditions and heart failure).
- **Neurodegenerative diseases:** The expression of EPAS1 and its interactions may play a role in the formation of the blood-brain barrier and its integrity during aging, potentially affecting diseases like Alzheimer's and other dementias.

### 3. Drug Interactions:
While there are no specific drugs directly targeting EPAS1, a few drug classes and compounds that indirectly interact or modulate the hypoxic response regulated by EPAS1 include:

- **Hypoxia-inducible factor (HIF) stabilizers:** Such as roxadustat (FG-4592) and vadadustat, which are being developed for anemia related to chronic kidney disease (CKD) and may modulate EPAS1 activity indirectly.
- **Anticancer agents:** Some chemotherapeutics that impact angiogenesis may also have interactions affecting EPAS1-mediated pathways (e.g., anti-VEGF therapies).
- **Anti-inflammatory drugs:** Agents that reduce hypoxia-induced inflammation may indirectly modulate the activity of EPAS1.

### 4. Pathways and Biological Processes:
EPAS1 is involved in several critical biological pathways and processes, including:

- **Hypoxia signaling pathway:** Modulates cellular responses to decreased oxygen levels.
- **Angiogenesis:** Involved in the regulation of blood vessel formation, particularly through the induction of VEGF.
- **Erythropoiesis:** Influences the production of red blood cells via erythropoietin signaling under hypoxic conditions.
- **Development of the vascular system:** Implicated in the formation of the endothelium and growth patterns of vascular networks.
- **Development of the blood-brain barrier:** Plays a role in endothelial cell differentiation and integrity.

Through these interactions and pathways, EPAS1 represents a critical factor in both normal physiological responses to hypoxia and various pathological conditions, making it a significant focus for further research into disease mechanisms and therapeutic strategies.