### KIR2DL3 Gene Overview

**Gene Symbol**: KIR2DL3  
**Gene Location**: Chromosome 19q13.4 (Leukocyte Receptor Complex - LRC)

The KIR2DL3 gene encodes a member of the Killer Immunoglobulin-like Receptor (KIR) family, specifically one that contains two extracellular immunoglobulin-like domains and possesses a long cytoplasmic tail, which is critical for its role as an inhibitory receptor on natural killer (NK) cells.

#### 1. Associated Genes
KIR2DL3 is part of the KIR gene cluster, which includes, but is not limited to, the following genes:
- **KIR2DL1**: Another inhibitory receptor with a similar function to KIR2DL3, recognizing distinct HLA-C alleles.
- **KIR2DS1**: An activating receptor that recognizes HLA-C molecules.
- **KIR3DL1**: Inhibitory receptor that has a longer domain and recognizes HLA-B molecules.
- **KIR3DS1**: Activating receptor associated with HLA-B molecules.
- **KIR3DL2**: Inhibitory receptor that recognizes HLA-A and HLA-B.

Additionally, KIR2DL3 is known to interact indirectly with other immune-modulating genes, particularly within the broader context of the human leukocyte antigen (HLA) system, affecting various immune responses.

#### 2. Aging and Age-related Diseases
- **Immune Evasion**: The KIR family, including KIR2DL3, is implicated in the immune response's alteration with aging. As individuals age, the balance of activating and inhibitory signals from KIRs can affect NK cell functionality, potentially leading to decreased immune surveillance and increased susceptibility to infections and malignancies.
- **Cancer Prognosis**: Variations in KIR genes, including KIR2DL3, have been associated with cancer prognosis and outcomes due to their role in regulating NK cell activity against tumor cells. Studies suggest that KIR2DL3 expression may correlate with the immune landscape of tumors and patient outcomes in several malignancies.

#### 3. Drug Interactions
While specific drugs that directly target KIR2DL3 are not extensively characterized, the following classes may have indirect implications for KIR signaling:
- **Immune Checkpoint Inhibitors**: Drugs that enhance NK cell activity may affect KIR signaling, including those targeting PD-1/PD-L1 pathways.
- **Monoclonal Antibodies**: Some therapies targeting HLA molecules or designed to modulate NK cell activity might indirectly interact with the KIR system.
- **Cytokines**: Treatments involving cytokines such as IL-15 have stimulatory effects on NK cell differentiation and might promote altered KIR expression.

#### 4. Pathways and Biological Processes
KIR2DL3 participates in several key biological pathways and processes, including:
- **Natural Killer Cell Activation**: KIR2DL3 plays a crucial role in the inhibition of NK cell activity when binding to HLA-C alleles. This is important in preventing autoimmunity and regulating immune responses to pathogens.
- **Immune System Regulation**: The interaction of KIR2DL3 with HLA-C molecules contributes to immune tolerance and homeostasis, crucial in maintaining a balance between activation and inhibition within the immune system.
- **Cell-Cell Signaling**: KIR2DL3 is involved in the transduction of inhibitory signals within immune synapses formed between NK cells and target cells, ultimately affecting cell lysis and immune response outcomes.

Understanding the function and interactions of KIR2DL3 contributes to insights into its role in health, immune responses, and its potential implications in various diseases, particularly in the context of cancer immunology and aging.