UNC13A Protein

UNC13A Protein

Introduction

Unc13A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@diekstra2014]
<table> [@rosen1993]
<tr><th colspan="2">UNC13A Protein</th></tr> [@sdhof2013]
<tr><td>Protein Name</td><td>Unc-13 Homolog A (Munc13-1)</td></tr> [@rizo2018]
<tr><td>Gene</td><td>[UNC13A](/genes/unc13a)</td></tr>
<tr><td>UniProt</td><td>[Q9UPN3](https://www.uniprot.org/uniprot/Q9UPN3)</td></tr>
<tr><td>Molecular Weight</td><td>220 kDa</td></tr>
<tr><td>Subcellular Localization</td><td>Synaptic vesicle presynaptic terminal</td></tr>
<tr><td>Protein Family</td><td>Munc13 homology domain protein family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">83 edges</a></td>
</tr>
</table>
</div>

Overview

UNC13A Protein

Introduction

Unc13A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@diekstra2014]
<table> [@rosen1993]
<tr><th colspan="2">UNC13A Protein</th></tr> [@sdhof2013]
<tr><td>Protein Name</td><td>Unc-13 Homolog A (Munc13-1)</td></tr> [@rizo2018]
<tr><td>Gene</td><td>[UNC13A](/genes/unc13a)</td></tr>
<tr><td>UniProt</td><td>[Q9UPN3](https://www.uniprot.org/uniprot/Q9UPN3)</td></tr>
<tr><td>Molecular Weight</td><td>220 kDa</td></tr>
<tr><td>Subcellular Localization</td><td>Synaptic vesicle presynaptic terminal</td></tr>
<tr><td>Protein Family</td><td>Munc13 homology domain protein family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">83 edges</a></td>
</tr>
</table>
</div>

Overview

UNC13A (also known as Munc13-1) is a large presynaptic protein essential for synaptic vesicle priming and neurotransmitter release. It plays a critical role in the molecular cascade leading to synaptic vesicle fusion with the presynaptic membrane. UNC13A is encoded by the UNC13A gene, and polymorphisms in this gene are associated with increased risk for amyotrophic lateral sclerosis (ALS), linking synaptic dysfunction to motor neuron degeneration^[1].

Structure

UNC13A contains multiple distinct domains:

Normal Function

UNC13A is essential for synaptic transmission:

Molecular Mechanism

UNC13A functions through several mechanisms:

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

UNC13A is a major ALS risk gene:

• Risk Variants: Intronic polymorphisms increase ALS risk by 1.3-1.5 fold^[2]
• Mechanism: Risk variants alter UNC13A expression and splicing
• Motor [Neuron](/entities/neurons) Vulnerability: Disrupted synaptic vesicle priming contributes to excitotoxicity
• Frontotemporal Dementia: Shared genetic risk between ALS and FTD

Other Neurological Disorders

• Autism Spectrum Disorder: Rare variants in UNC13A
• Epilepsy: Altered vesicle priming in some forms
• Schizophrenia: Genetic associations in some populations

Therapeutic Approaches

Targeting UNC13A-related pathways:

Research Directions

Key areas of investigation:

• Understanding how ALS risk variants affect UNC13A function
• Developing therapies to restore synaptic vesicle priming
• Biomarkers for synaptic dysfunction in ALS
• Links between UNC13A and other ALS genes ([C9orf72](/entities/c9orf72), TDP-43)

Background

The study of Unc13A Protein 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

[^

See Also

• UNC1- Synaptic Dysfunction Pathway
• Synaptic Vesicle Proteins
• [Motor Neurons](/cell-types/motor-neurons)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)

External Link

• [UniProt: UNC13A](https://www.uniprot.org/uniprot/Q9UPN3)
• [GeneCards: UNC13A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=UNC13A)
• [OMIM: UNC13A](https://www.omim.org/entry/614715)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving UNC13A Protein discovered through SciDEX knowledge graph analysis: