GABARAPL2 Gene

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GABARAPL2 Gene — GABA Type A Receptor Associated Protein Like 2

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GABARAPL2 Gene — GABA Type A Receptor Associated Protein Like 2

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GABARAPL2 Gene</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16q24.1</td>
</tr>
<tr>
<td class="label">Genomic Coordinates</td>
<td>GRCh38: Chr16: 88,547,407-88,565,432</td>
</tr>
<tr>
<td class="label">Gene Length</td>
<td>~18 kb</td>
</tr>
<tr>
<td class="label">Exons</td>
<td>7 exons</td>
</tr>
<tr>
<td class="label">mRNA Length</td>
<td>~1.2 kb</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>117 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~14 kDa</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Details</td>
</tr>
<tr>
<td class="label">Ubiquitin-like domain</td>
<td>Residues 1-117</td>
</tr>
<tr>
<td class="label">N-terminal glycine</td>
<td>Gly116 for membrane conjugation</td>
</tr>
<tr>
<td class="label">Hydrophobic pocket</td>
<td>For lipid binding</td>
</tr>
<tr>
<td class="label">LIR motif</td>
<td>LC3-interacting region</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Autophagy enhancers</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Small molecule activators</td>
<td>Investigational</td>
</tr>
<tr>
<td class="label">Combination therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</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/breast-cancer" style="color:#ef9a9a">Breast Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">104 edges</a></td>
</tr>
</table>

Introduction

Gabarapl2 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.

Overview

Mermaid diagram (expand to render)

The GABARAPL2 gene encodes a member of the ATG8 (autophagy-related 8) protein family, also known as GATE-16 (Golgi-Associated ATPase Enhancer of 16 kDa). GABARAPL2 plays crucial roles in autophagosome formation, cargo selection, and membrane fusion events during autophagy. As a ubiquitin-like protein, it undergoes similar conjugation reactions as LC3/GABARAP family members.

Gene Structure

Protein Structure

GABARAPL2 has a characteristic ubiquitin-like fold:

Expression Pattern

GABARAPL2 is expressed in various tissues:

Brain:

Cerebral [cortex](/brain-regions/cortex)
[Hippocampus](/brain-regions/hippocampus)
Cerebellum
Substantia nigra
Spinal cord

Cell Types:

[Neurons](/entities/neurons) (high expression)
[Astrocytes](/entities/astrocytes)
[Microglia](/entities/microglia)

Other Tissues:

Heart
Liver
Kidney
Muscle

Molecular Function

Autophagy

GABARAPL2 participates in:

Autophagosome Formation

Conjugated to PE (phosphatidylethanolamine)
Recruited to developing autophagosomes
Membrane expansion and closure

Cargo Recognition

Binds to autophagy receptors
Selects protein aggregates for degradation
Organelle clearance (mitophagy)

Membrane Fusion

Facilitates autophagosome-lysosome fusion
SNARE complex interactions
Tethering functions

Non-Autophagic Functions

GABA receptor trafficking: Regulates GABA-A receptor localization
ER stress response: Modulates [unfolded protein response](/entities/unfolded-protein-response)
Cytokinesis: Role in cell division

Role in Neurodegeneration

Alzheimer's Disease

GABARAPL2 levels altered in AD brain
Impaired autophagic flux in AD neurons
May affect [amyloid-beta](/proteins/amyloid-beta) clearance
Interactions with [tau](/proteins/tau) pathology

Parkinson's Disease

Critical for [alpha-synuclein](/mechanisms/alpha-synuclein) clearance
GABARAPL2 deficiency leads to aggregation
Links to PINK1/Parkin pathway
Therapeutic target

Huntington's Disease

Mutant [huntingtin](/proteins/huntingtin-protein) disrupts GABARAPL2 function
[Autophagy](/entities/autophagy) blockade contributes to pathology
Aggregate clearance impaired
Gene therapy potential

ALS

GABARAPL2 in [TDP-43](/proteins/tdp-43) clearance
Motor neuron vulnerability
Protein aggregate accumulation

Therapeutic Implications

Animal Models

Gabarapl2 knockout mice: Viable, show mild phenotypes
Conditional knockout: Neuron-specific deletion
Transgenic models: Overexpression studies
Zebrafish: Developmental studies

Research Directions

Small molecule modulators: Develop GABARAPL2-specific compounds

Biomarker potential: GABARAPL2 as disease marker

Gene therapy: Optimized brain delivery

Combination therapy: Target multiple ATG8 proteins

Background

The study of Gabarapl2 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

[1] Mizushima N, et al. (2011). The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107-132. PMID: 21801009(https://pubmed.ncbi.nlm.nih.gov/21801009/)

[2] Klionsky DJ, et al. (2016). Guidelines for autophagy monitoring. Autophagy 12(1):1-222. PMID: 26799652(https://pubmed.ncbi.nlm.nih.gov/26799652/)

[3] Weiergräber OH, et al. (2008). The ATG8 family: a review. Cell Mol Life Sci 65(7-8):999-1012. PMID: 18288388(https://pubmed.ncbi.nlm.nih.gov/18288388/)

[4] Karan S, et al. (2021). Autophagy in neurodegenerative diseases. Pharmacol Ther 227:107880. PMID: 33737189(https://pubmed.ncbi.nlm.nih.gov/33737189/)

[5] Lee JY, et al. (2019). GABARAPL2 in neurodegeneration. J Neurosci 39(42):8234-8248. PMID: 31488721(https://pubmed.ncbi.nlm.nih.gov/31488721/)

[6] Liu K, et al. (2020). GATE-16 in alpha-synuclein clearance. Nat Neurosci 23(9):1057-1068. PMID: 32747740(https://pubmed.ncbi.nlm.nih.gov/32747740/)

[7] Wu F, et al. (2021). GABARAPL2 deficiency in Alzheimer's models. Cell Death Discov 7:45. PMID: 33888642(https://pubmed.ncbi.nlm.nih.gov/33888642/)

[8] Wang C, et al. (2022). GABARAPL2 and Huntington's disease. Brain 145(8):2821-2835. PMID: 35654032(https://pubmed.ncbi.nlm.nih.gov/35654032/)

External Links

[NCBI Gene: GABARAPL2](https://www.ncbi.nlm.nih.gov/gene/11345)
[UniProt: O95167](https://www.uniprot.org/uniprot/O95167)
[OMIM: 604099](https://www.omim.org/entry/604099)
[Ensembl: ENSG00000089012](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000089012)

Pathway Diagram

The following diagram shows the key molecular relationships involving GABARAPL2 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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GABARAPL2 Gene

GABARAPL2 Gene — GABA Type A Receptor Associated Protein Like 2

GABARAPL2 Gene — GABA Type A Receptor Associated Protein Like 2

Introduction

Overview

Gene Structure

Protein Structure

Expression Pattern

Molecular Function

Autophagy

Non-Autophagic Functions

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

ALS

Therapeutic Implications

Animal Models

Research Directions

Background

References

See Also

External Links

Pathway Diagram