GABRA6 Protein

GABRA6 Protein

Introduction

Gabra6 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"> [@mohler2007]
<table> [@rudolph2010]
<tr><th colspan="2" style="background:#f0f0f0;">Protein Overview</th></tr> [@luscher2011]
<tr><td><strong>Protein Name</strong></td><td>GABA-A Receptor Alpha6 Subunit</td></tr> [@brickley2012]
<tr><td><strong>Gene</strong></td><td>GABRA6</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>P47870</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6HUP, 6D6U</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~56 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cell membrane (ion channel)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Cys-loop receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

The GABRA6 protein encodes the alpha-6 subunit of the GABA-A receptor. This subunit contributes to inhibitory synaptic transmission, particularly in cerebellar and hippocampal [neurons](/entities/neurons). GABRA6 variants have been associated with epilepsy, ataxia, and autism spectrum disorders.

Structure

GABRA6 protein is a ligand-gated chloride channel subunit. Key structural features:

GABRA6 Protein

Introduction

Gabra6 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"> [@mohler2007]
<table> [@rudolph2010]
<tr><th colspan="2" style="background:#f0f0f0;">Protein Overview</th></tr> [@luscher2011]
<tr><td><strong>Protein Name</strong></td><td>GABA-A Receptor Alpha6 Subunit</td></tr> [@brickley2012]
<tr><td><strong>Gene</strong></td><td>GABRA6</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>P47870</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6HUP, 6D6U</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~56 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cell membrane (ion channel)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Cys-loop receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

The GABRA6 protein encodes the alpha-6 subunit of the GABA-A receptor. This subunit contributes to inhibitory synaptic transmission, particularly in cerebellar and hippocampal [neurons](/entities/neurons). GABRA6 variants have been associated with epilepsy, ataxia, and autism spectrum disorders.

Structure

GABRA6 protein is a ligand-gated chloride channel subunit. Key structural features:

• N-terminal extracellular domain: Contains the GABA binding site
• Transmembrane domain: 4 alpha helices (M1-M4) forming the ion channel pore
• C-terminal intracellular domain: Contains phosphorylation sites
• Disulfide loop ("Cys-loop"): Signature motif of the receptor family

Normal Function

The alpha6 subunit-containing GABA-A receptors mediate:

Pharmacological properties:

• High affinity for GABA
• Modulated by neurosteroids
• Distinct benzodiazepine binding profile (alpha6-containing receptors are benzodiazepine-insensitive)

Role in Disease

Alzheimer's Disease

• Reduced GABRA6 expression in cerebellum
• Loss of inhibitory balance may contribute to network dysfunction
• Cerebellar involvement in AD progression

Parkinson's Disease

• Altered GABAergic signaling in basal ganglia output nuclei
• Potential for GABAergic therapeutic modulation
• Motor coordination effects

Epilepsy

• GABRA6 mutations can cause epilepsy phenotypes
• Altered inhibitory tone
• Anti-seizure drug targets

Cerebellar Ataxias

• Critical for cerebellar cortical function
• Spinocerebellar ataxia type 19 linked to GABRA6
• Motor coordination deficits

Autism

• Altered inhibitory/excitatory balance
• Sensory processing differences

Therapeutic Targeting

| Approach | Status | Notes |
|----------|--------|-------|
| GABA-A modulators | Clinical | Benzodiazepines not effective on alpha6 |
| Neurosteroid modulators | Research | Positive allosteric modulators |
| Gene therapy | Preclinical | AAV-GABRA6 delivery |
| Cell therapy | Preclinical | GABAergic neuron transplantation |

Expression Pattern

Disease Associations

Therapeutic Implications

Animal Models

Background

The study of Gabra6 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.

See Also

• [GABRA6 Gene](/genes/gabra6)
• GABA-A Receptor Pathway
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [UniProt: P47870](https://www.uniprot.org/uniprot/P47870)
• [PDB: 6HUP](https://www.rcsb.org/structure/6HUP)
• [NCBI Protein: NP_000800](https://www.ncbi.nlm.nih.gov/protein/NP_000800)

References