BRCA2 Gene

BRCA2 Gene

Introduction

Brca2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@caldecott2008]
title: BRCA2 Gene [@mckinnon2009]

--- [@kennedy2010]

<div class="infobox infobox-gene"> [@madabhushi2014]

| | |
|---|---|
| Gene Symbol | BRCA2 |
| Full Name | BRCA2 DNA Repair Associated |
| Chromosomal Location | 13q13.1 |
| NCBI Gene ID | [675](https://www.ncbi.nlm.nih.gov/gene/675) |
| Ensembl ID | [ENSG00000139618](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139618) |
| OMIM ID | 600185 |
| UniProt ID | [P51587](https://www.uniprot.org/uniprotkb/P51587/entry) |

</div>

Overview

BRCA2 Gene

Introduction

Brca2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@caldecott2008]
title: BRCA2 Gene [@mckinnon2009]

--- [@kennedy2010]

<div class="infobox infobox-gene"> [@madabhushi2014]

| | |
|---|---|
| Gene Symbol | BRCA2 |
| Full Name | BRCA2 DNA Repair Associated |
| Chromosomal Location | 13q13.1 |
| NCBI Gene ID | [675](https://www.ncbi.nlm.nih.gov/gene/675) |
| Ensembl ID | [ENSG00000139618](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139618) |
| OMIM ID | 600185 |
| UniProt ID | [P51587](https://www.uniprot.org/uniprotkb/P51587/entry) |

</div>

Overview

BRCA2 is a tumor suppressor protein essential for homologous recombination (HR) repair of DNA double-strand breaks. It interacts with RAD51 to promote strand invasion and exchange during HR. Beyond cancer, BRCA2 deficiency leads to increased genomic instability in [neurons](/entities/neurons) and has been implicated in neurodegenerative diseases.

Normal Function

The BRCA2 gene encodes BRCA2 DNA Repair Associated, involved in DNA repair and genomic stability:

• DNA repair: Critical for maintaining genomic integrity
• Cell cycle regulation: Coordinates DNA repair with cell cycle progression
• [Apoptosis](/entities/apoptosis): Modulates apoptotic response to DNA damage
• Neuronal survival: Essential for long-term neuronal survival

Expression Pattern

BRCA2 is expressed in:

• [Hippocampus](/brain-regions/hippocampus)
• Cerebral [cortex](/brain-regions/cortex)
• Testis
• Ovary
• Ubiquitous

Disease Associations

BRCA2 is implicated in:

| Disease | Association Type | Evidence |
|---------|------------------|----------|
| Alzheimer's Disease | Genetic/Expression | 6174delT |
| Parkinson's Disease | Genetic/Expression | 6174delT |
| Amyotrophic Lateral Sclerosis | Genetic/Expression | 6174delT |
| Breast/Ovarian Cancer | Genetic/Expression | 6174delT |

Key Mutations/Variants

• 6174delT: functional studies
• S2670L: functional studies
• K3326X: functional studies
• N372H: functional studies

Therapeutic Implications

BRCA2 is relevant for therapeutic development:

• Neurodegenerative diseases: DNA repair deficits contribute to neuronal dysfunction
• Cancer therapy: PARP inhibitors are synthetically lethal with BRCA2 deficiency
• Aging: DNA repair decline is a hallmark of aging and neurodegeneration
• Radiosensitivity: DNA repair capacity affects neuronal survival after injury

Therapeutic Strategies

| Strategy | Approach | Status |
|----------|----------|--------|
| Gene therapy | AAV-based delivery | Preclinical |
| Small molecules | DNA repair enhancers | Research |
| Combination therapy | PARP inhibitors + radiation | Clinical (cancer) |

Key Publications

See Also

• [DNA Damage Response Pathway](/mechanisms/dna-damage-response)
• [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Genomic Instability](/mechanisms/genomic-instability)

External Links

• [NCBI Gene: BRCA2](https://www.ncbi.nlm.nih.gov/gene/675)
• [UniProt: BRCA2](https://www.uniprot.org/uniprotkb/P51587/entry)
• [HGNC: BRCA2](https://www.genenames.org/data/hgnc_complete_set/)
• [GeneCards: BRCA2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA2)

Animal Models

BRCA2 knockout mice exhibit embryonic lethality, while conditional knockout models show increased genomic instability in neurons. BRCA2-deficient neural progenitor cells demonstrate impaired DNA repair and increased sensitivity to genotoxic stress. Transgenic models overexpressing wild-type BRCA2 show improved neuronal survival after DNA damage. These models have been used to study the role of BRCA2 in neurodegeneration and potential therapeutic interventions.

Research Directions

Current research focuses on understanding how BRCA2 mutations contribute to neurodegeneration, the relationship between cancer predisposition and neurodegenerative diseases, and developing gene therapy approaches to restore BRCA2 function in neurons. Additionally, studies are investigating the use of BRCA2 as a biomarker for DNA repair capacity in neurodegenerative diseases.

Background

The study of Brca2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

Pathway Diagram

The following diagram shows the key molecular relationships involving BRCA2 Gene discovered through SciDEX knowledge graph analysis: