### NCOA3 Gene Overview

**Gene Symbol:** NCOA3  
**Location:** Human gene located on chromosome 20q12

### 1. Associated Genes
While the provided summaries mention several nuclear hormone receptors (e.g., GR, ER, RARs, RXRs, TRs, VDR, PPARs, and NFKB1), NCOA3 may also be associated with other genes involved in transcription regulation and coactivation, such as:

- **NCOA1 (Nuclear Receptor Coactivator 1)** — another coactivator that works with nuclear receptors.
- **NCOA2 (Nuclear Receptor Coactivator 2)** — closely related to NCOA3 and shares similar functions.
- **CBP (CREB-binding protein)** and **p300** — two well-characterized histone acetyltransferases that form complexes with NCOA3.
- **TERT (telomerase reverse transcriptase)** — studies have linked NCOA3 to cellular aging through telomerase regulation.
- **SIRT1** — as part of the aging research where NCOA3 is interacting and modulating signaling pathways pertinent to longevity.

### 2. Aging and Age-Related Diseases
NCOA3 has been implicated in several age-related processes and conditions:

- **Cancer:** NCOA3 overexpression has been associated with various cancers, particularly breast and prostate cancer. Its role as a coactivator for nuclear hormone receptors is critical in the transcriptional regulation of growth-promoting genes.
- **Obesity and Metabolic Disorders:** NCOA3 may affect metabolic signal transduction pathways. Alterations in its function may relate to obesity, insulin resistance, and other metabolic syndromes.
- **Neurodegenerative Diseases:** There is emerging evidence that suggests a potential link between NCOA3 and neurodegenerative diseases, as alterations in nuclear receptor signaling pathways can influence neuronal health and function.
- **Hormone-Dependent Aging:** Given its role in coactivation with steroid receptors, mutations or variations may influence aging processes connected to hormonal changes.

### 3. Drug Interactions
NCOA3 interacts with various drugs, particularly those targeting nuclear hormone receptors. Some notable examples include:

- **Selective Estrogen Receptor Modulators (SERMs)** such as Tamoxifen and Raloxifene, which may be impacted by the presence of NCOA3 in enhancing the estrogenic effects.
- **Corticosteroids** (e.g., Prednisone) that bind to the glucocorticoid receptor (GR).
- **Retinoids** used in oncology and dermatology which interact with retinoic acid receptors (RARs).
- **Glitazones** (e.g., Rosiglitazone) that act via peroxisome proliferator-activated receptors (PPARs).
- **Drugs targeting the NF-kappa-B pathway**, where NCOA3 may influence responsiveness to anti-inflammatory treatments.

### 4. Pathways and Biological Processes
NCOA3 is involved in several significant biological pathways:

- **Nuclear Receptor Signaling Pathway:** It plays a crucial role in enhancing transcriptional responses mediated by steroid hormones, retinoids, and other ligands.
- **Histone Acetylation:** NCOA3 exhibits histone acetyltransferase activity, influencing chromatin remodeling and facilitating gene transcription.
- **Signal Transduction Pathways:** It interacts with various signaling pathways, including the NF-kappa-B pathway, modulating immune responses and inflammation.
- **Cell Cycle Regulation:** As a coactivator of estrogen and androgen receptors, it may influence genes regulating proliferation and cell cycle progression.
- **Regulation of Lipid Metabolism:** NCOA3 plays a role in regulating lipid metabolism through interactions with PPARs.

### Conclusion
NCOA3 is a multifaceted gene with significant roles in transcriptional regulation, interactions with several nuclear receptors, and implications in aging and disease processes. Its involvement in critical pathways emphasizes its importance in both physiological and pathological conditions. Further research continues to elucidate its roles in health and disease, especially concerning cancer and metabolic disorders.