### ORAI3 Gene Overview

**Gene Symbol:** ORAI3  
**Location:** Plasma membrane  
**Function:** Store-operated calcium channel activity, involved in store-operated calcium entry. Functions synergistically with the calcium sensor STIM1 to mediate Ca²⁺ influx and enhance Ca²⁺-selective current.

#### 1. Associated Genes
ORAI3 interacts with several other genes, including:
- **STIM1:** A critical calcium sensor that regulates the activity of ORAI3 and other ORAI family proteins.
- **ORAI1 and ORAI2:** Other members of the ORAI gene family that also contribute to Ca²⁺ influx and store-operated calcium entry.
- **TRPC (Transient Receptor Potential Canonical) channels:** They may have functional association with ORAI3 in calcium signaling pathways.
- **CALM (Calmodulin):** Plays a role in Ca²⁺ signaling and may interact with calcium channels including those formed by ORAI proteins.

#### 2. Aging and Age-Related Diseases
Research has indicated that dysregulation of calcium signaling, including the function of calcium channels like ORAI3, is associated with several age-related diseases:
- **Neurodegenerative diseases:** Alterations in calcium homeostasis are implicated in conditions like Alzheimer's disease and Parkinson's disease.
- **Cardiovascular diseases:** Abnormal calcium signaling can affect cardiac myocyte function, potentially leading to age-related cardiac dysfunction.
- **Osteoporosis:** Calcium channels are critical in bone remodeling, and changes in their function may contribute to the development of osteoporosis in aging populations.

#### 3. Drug Interactions
Several drugs and drug classes may interact with the ORAI3 gene:
- **Calcium channel blockers:** Although specific to voltage-gated calcium channels, some may indirectly influence ORAI3 activity due to alterations in intracellular calcium levels.
- **STIM1 activators/inhibitors:** Modulating STIM1 activity will affect ORAI3-mediated calcium influx.
- **Immunosuppressive drugs:** Certain drugs targeting calcium signaling pathways may influence immune responses by interacting with ORAI channels.

#### 4. Pathways and Biological Processes
ORAI3 participates in several critical biological pathways:
- **Store-operated calcium entry (SOCE):** A fundamental process allowing cells to replenish calcium stores after depletion.
- **Calcium signaling pathways:** Involvement in signaling cascades that regulate various cellular functions, including muscle contraction, neurotransmitter release, and gene expression.
- **Immune response:** Plays a role in the activation of immune cells through calcium influx, affecting T cell activation and function.
- **Cell proliferation and differentiation:** Alterations in calcium entry can influence these processes, impacting cellular responses to external signals.
- **Apoptosis and cell survival pathways:** Calcium dysregulation can affect the balance between cell survival and apoptosis, particularly in cancer biology.

### Summary
The ORAI3 gene is crucial for calcium signaling and plays significant roles in various physiological and pathological processes. Understanding its interactions and functions further informs its implications in health and disease, particularly concerning aging and age-related conditions.