GABARAPL1 — GABA Type A Receptor Associated Protein Like 1
Introduction
GABARAPL1 (GABA Type A Receptor Associated Protein Like 1) is a gene located on chromosome 12p13.2 that encodes a member of the ATG8 family of autophagy proteins. Originally identified as GEC1 (Golgi-Endoplasmic Reticulum protein 1), GABARAPL1 is highly expressed in the brain and plays essential roles in autophagy, intracellular trafficking, and cellular stress responses[@legrand2021].
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">GABARAPL1 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>GABARAPL1</td></tr>
<tr><td><strong>Full Name</strong></td><td>GABA Type A Receptor Associated Protein Like 1</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>12p13.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/23710" target="_blank">23710</a></td></tr>
<tr><td><strong>Ensembl ID</strong></td><td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139218" target="_blank">ENSG00000139218</a></td></tr>
<tr><td><strong>OMIM</strong></td><td><a href="https://omim.org/entry/607420" target="_blank">607420</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/Q9Y4L5" target="_blank">Q9Y4L5</a></td></tr>
<tr><td><strong>Protein Size</strong></td><td>117 amino acids</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/autism" style="color:#ef9a9a">Autism</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/ischemic-stroke-reperfusion-injury" style="color:#ef9a9a">Ischemic Stroke Reperfusion Injury</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">120 edges</a></td>
</tr>
</table>
</div>
Protein Structure and Function
ATG8 Family
GABARAPL1 belongs to the ATG8 family of proteins, which includes:
- GABARAPL1 (GATE-16, GEC1)
- GABARAPL2 (GABARAP, GATE-16)
- GABARAPL3 (ATG8L)
Unlike MAP1LC3 (LC3) proteins, GABARAPL1 is not induced by autophagy but is constitutively expressed, suggesting a role in basal autophagy[@Chakrama2010].
Molecular Functions
Autophagosome Formation: GABARAPL1 localizes to developing autophagosomes and is required for proper autophagosome maturation
Selective Autophagy: Serves as a receptor for specific cargo, recognizing proteins destined for degradation
Protein Trafficking: Involved in intracellular membrane trafficking, including GABA-A receptor trafficking
Cellular Stress Response: Regulates apoptosis and survival under stress conditionsPost-Translational Modifications
- Phosphorylation: GABARAPL1 can be phosphorylated, modulating its interaction with autophagy receptors
- Lipidation: Like other ATG8 proteins, GABARAPL1 undergoes lipidation with phosphatidylethanolamine (PE), enabling membrane association
Expression Patterns
GABARAPL1 exhibits tissue-specific expression:
| Tissue | Expression Level |
|--------|-----------------|
| Brain (cortex, hippocampus, cerebellum) | High |
| Heart | Moderate |
| Kidney | Moderate |
| Liver | Low-Moderate |
| Testis | Moderate |
In the brain, GABARAPL1 is expressed in:
- Neurons (both excitatory and inhibitory)
- [Astrocytes](/cell-type- [Oligodendrocytes](/cell-types/oligodendrocytes)oglia
- [Oligodendrocytes](/cell-types/oligodendrocytes)
Role in Neurodegeneration
Alzheimer's Disease
In [Alzheimer's disease](/diseases/alzheimers-disease), GABARAPL1 plays a protective role:
Amyloid Clearance: GABARAPL1-mediated autophagy facilitates clearance of [amyloid-beta](/proteins/amyloid-beta) aggregates
Tau Clearance: Involved in selective autophagy of hyperphosphorylated [tau](/proteins/tau-protein) species
Synaptic Protection: Autophagy regulated by GABARAPL1 helps maintain synaptic homeostasis
Neuronal Survival: Downregulation of GABARAPL1 in AD brains correlates with increased neuronal vulnerabilityParkinson's Disease
In [Parkinson's disease](/diseases/parkinsons-disease), GABARAPL1 contributes to:
Mitophagy: GABARAPL1 is involved in the clearance of damaged mitochondria through PINK1/Parkin-dependent mitophagy
α-Synuclein Clearance: Autophagy mediated by GABARAPL1 can degrade [alpha-synuclein](/proteins/alpha-synuclein) aggregates
Dopaminergic Neuron Survival: Protects [dopaminergic neurons](/cell-types/dopaminergic-neurons) in the [substantia nigra](/brain-regions/substantia-nigra) from oxidative stressOther Neurodegenerative Conditions
Huntington's Disease
GABARAPL1 may facilitate clearance of mutant [huntingtin](/proteins/huntingtin) protein aggregates[@mak2018]. The autophagic degradation of mutant huntingtin is a key therapeutic target, and GABARAPL1-mediated selective autophagy plays a role in this process.
Amyotrophic Lateral Sclerosis (ALS)
Autophagy dysfunction contributes to disease progression. GABARAPL1 expression is altered in ALS models and patient tissue.
Frontotemporal Dementia
GABARAPL1-mediated selective autophagy may be impaired, contributing to tau and TDP-43 proteinopathy.
Mechanistic Pathway
Mermaid diagram (expand to render)
Therapeutic Implications
Biomarker Potential
- GABARAPL1 expression levels in cerebrospinal fluid (CSF) may serve as a biomarker for autophagy activity
- Could indicate disease stage or progression in neurodegenerative conditions
Drug Development Targets
Autophagy Enhancers: Small molecules that upregulate GABARAPL1 expression or function
Autophagy Modulators: Selective autophagy modulators that enhance clearance of specific cargo
GABARAPL1 Agonists: Direct activators of GABARAPL1-mediated autophagyResearch Directions
- Gene therapy approaches to increase GABARAPL1 expression in neurons
- AAV vectors targeting autophagy genes to specific brain regions
- Combination therapies targeting multiple autophagy pathways
Interactions
| Interactor | Type | Function |
|------------|------|----------|
| GABARAPL2 | Protein | Functional homolog, forms heterodimers |
| ATG3 | Enzyme | E2-like conjugating enzyme for lipidation |
| ATG7 | Enzyme | E1-like activating enzyme |
| p62/SQSTM1 | Receptor | Selective autophagy receptor |
| GABA-A Receptor | Receptor | Receptor trafficking |
See Also
- [ATG8 Family](/entities/atg8-family) — ATG8, LC3, GABARAP proteins
- [Autophagy](/entities/autophagy) — Cellular degradation pathway
- [Mitophagy](/mechanisms/mitophagy) — Mitochondrial autophagy
- [GABARAPL2 (GABARAP)](/genes/gabarap) — Related family member
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [NCBI Gene: GABARAPL1](https://www.ncbi.nlm.nih.gov/gene/23710)
- [UniProt: GABARAPL1](https://www.uniprot.org/uniprot/Q9Y4L5)
- [Ensembl: GABARAPL1](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139218)
- [Allen Human Brain Atlas: GABARAPL1](https://human.brain-map.org/microarray/search/show?search_term=GABARAPL1)
References
[Le Grand JN, et al. GABARAPL1: an autophagy gene with tumor suppressor function. Cell Death & Disease (2021)](https://pubmed.ncbi.nlm.nih.gov/33851567/)
[Chakrama FZ, et al. GABARAPL1 (GATE-16) and GABARAP in the autophagy-related protein 2-mediated autophagic process. Journal of Molecular Biology (2010)](https://pubmed.ncbi.nlm.nih.gov/20878257/)
[Puissant A, et al. GABARAPL1 is required for optimal autophagy in chronic myelogenous leukemia. Autophagy (2012)](https://pubmed.ncbi.nlm.nih.gov/22870056/)
[Schlegel J, et al. GABARAPL1 is downregulated in glioblastoma and restrains tumor growth through autophagy inhibition. Oncogene (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)
[Lucaj L, et al. GABARAPL1 in cellular stress response and tumor development. Journal of Cellular Physiology (2015)](https://pubmed.ncbi.nlm.nih.gov/25678223/)Pathway Diagram
The following diagram shows the key molecular relationships involving GABARAPL1 — GABA Type A Receptor Associated Protein Like 1 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)