### TGM3 Gene Overview

**Gene Symbol:** TGM3  
**Location:** Human Chromosome 20  
**Function:** The TGM3 gene encodes a member of the transglutaminase family of enzymes, which catalyze the formation of covalent bonds between proteins by cross-linking glutamine and lysine residues. This process is crucial for various structural aspects of the epidermis, particularly in forming the cornified envelope present in the outermost layer of skin cells.

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### 1. Associated Genes
While the summaries provide a concise overview of TGM3 functions, additional genes that are commonly associated with TGM3 in related pathways include:

- **TGM1:** Another transglutaminase involved in forming the cornified envelope in keratinocytes. TGM1 is closely related functionally to TGM3 since both play roles in skin barrier formation.
- **SPRR1 and SPRR2:** Small proline-rich proteins which are substrates for TGM3, involved in the structural integrity of the cornified envelope.
- **LOR (Loricrin):** A protein that is cross-linked by TGM3 and plays a critical role in skin barrier function.
- **KRT (Keratin) family members:** Various keratin genes that may interact with TGM3 during the development of the skin structure.

### 2. Aging or Age-related Disease Associations
While TGM3 has not been directly linked to specific age-related diseases, there are several pertinent points to consider:

- **Skin Aging:** The activity and expression levels of transglutaminases, including TGM3, may be altered with aging, which can affect skin elasticity and hydration. Reduced function might contribute to the deterioration of skin barrier properties, leading to age-associated skin conditions.
- **Psoriasis and Dermatitis:** Variations in TGM3 expression have been implicated in certain skin disorders, which can manifest more prominently with age. The skin’s ability to form a protective barrier may decline in these conditions.

### 3. Drug Interactions
Currently, specific pharmacological compounds solely targeting TGM3 are not well-documented. However, certain drug classes may influence its activity indirectly or alight pathways related to skin and epithelial integrity:

- **Retinoids:** Often used in dermatological formulations, may modulate skin turnover and potentially affect transglutaminase activities.
- **Topical Corticosteroids:** Commonly used for inflammatory skin diseases, they might alter the expression of TGM3 by affecting overall gene expression associated with the epidermal differentiation process.

### 4. Pathways and Biological Processes
TGM3 is involved in several biological processes and pathways:

- **Keratinization:** Plays a pivotal role in the differentiation of keratinocytes and the formation of the cornified envelope, which is vital for skin integrity.
- **Cell Adhesion:** Involved in cross-linking proteins that contribute to cell adhesion properties in epithelial tissues.
- **Pathways:** TGM3 is part of various signaling pathways that regulate keratinocyte differentiation, including:
  - The **Notch signaling pathway**, which regulates skin cell fate.
  - The **Wnt signaling pathway**, related to cell proliferation and differentiation in epithelial tissues.

### Summary
The TGM3 gene is essential for maintaining skin barrier function and structural integrity by cross-linking proteins in the epidermis and hair follicles. Its associations with other transglutaminase genes, potential roles in aging-related skin conditions, and involvement in several biological processes highlight its significance in skin biology. Current research is ongoing to better understand its implications in dermatology and possible therapeutic approaches.