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 molecu
...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 proteinsBackground
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
<sup>[1]</sup> 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/)
<sup>[2]</sup> Klionsky DJ, et al. (2016). Guidelines for autophagy monitoring. Autophagy 12(1):1-222. PMID: 26799652(https://pubmed.ncbi.nlm.nih.gov/26799652/)
<sup>[3]</sup> 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/)
<sup>[4]</sup> Karan S, et al. (2021). Autophagy in neurodegenerative diseases. Pharmacol Ther 227:107880. PMID: 33737189(https://pubmed.ncbi.nlm.nih.gov/33737189/)
<sup>[5]</sup> Lee JY, et al. (2019). GABARAPL2 in neurodegeneration. J Neurosci 39(42):8234-8248. PMID: 31488721(https://pubmed.ncbi.nlm.nih.gov/31488721/)
<sup>[6]</sup> 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/)
<sup>[7]</sup> 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/)
<sup>[8]</sup> Wang C, et al. (2022). GABARAPL2 and Huntington's disease. Brain 145(8):2821-2835. PMID: 35654032(https://pubmed.ncbi.nlm.nih.gov/35654032/)
See Also
- [GABARAPL2 Protein](/proteins/gabarapl2-protein)
- [GABARAP Protein](/proteins/gabarap-protein)
- [LC3 Protein](/proteins/lc3-protein)
- [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosome-neurodegeneration)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Huntington's Disease](/diseases/huntingtons-disease)
- [Genes Index](/genes)
- [Proteins Index](/proteins)
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)