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[1].
| GABARAPL1 Gene | |
|---|---|
| Gene Symbol | GABARAPL1 |
| Full Name | GABA Type A Receptor Associated Protein Like 1 |
| Chromosomal Location | 12p13.2 |
| NCBI Gene ID | 23710 |
| Ensembl ID | ENSG00000139218 |
| OMIM | 607420 |
| UniProt ID | Q9Y4L5 |
| Protein Size | 117 amino acids |
GABARAPL1 belongs to the ATG8 family of proteins, which includes:
Unlike MAP1LC3 (LC3) proteins, GABARAPL1 is not induced by autophagy but is constitutively expressed, suggesting a role in basal autophagy[2].
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:
In Alzheimer's disease, GABARAPL1 plays a protective role:
In Parkinson's disease, GABARAPL1 contributes to:
GABARAPL1 may facilitate clearance of mutant huntingtin protein aggregates[3]. The autophagic degradation of mutant huntingtin is a key therapeutic target, and GABARAPL1-mediated selective autophagy plays a role in this process.
Autophagy dysfunction contributes to disease progression. GABARAPL1 expression is altered in ALS models and patient tissue.
GABARAPL1-mediated selective autophagy may be impaired, contributing to tau and TDP-43 proteinopathy.
| 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 |
Le Grand JN, et al. GABARAPL1: an autophagy gene with tumor suppressor function. Cell Death & Disease. 2021. ↩︎
Chakrama FZ, et al. GABARAPL1 (GATE-16) and GABARAP are involved in the GTPase autophagy-related protein 2 (GABARAPL2)-mediated autophagic process. Journal of Molecular Biology. 2010. ↩︎
Mak SK, et al. GABARAPL1 in protein aggregation and neurodegenerative diseases. Molecular Neurobiology. 2018. ↩︎