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Target intelligence / Profile preview
Gamma-aminobutyric acid type A receptor alpha 6 subunit (GABRA6) (GABRA6)
- Target
- GABRA6
- Molecular classification
- Ion channel, Ligand-gated ion channel, Cys-loop receptor family, GABA receptor
01
Overview
The Gamma-aminobutyric acid type A receptor alpha 6 subunit (GABRA6) is a critical component of pentameric ligand-gated chloride channels that mediate fast inhibitory neurotransmission in the central nervous system. Unlike other alpha subunits, the alpha 6 isoform is highly localized, primarily expressed in the cerebellar granule cells and the cochlear nucleus, where it contributes significantly to tonic inhibition rather than just phasic synaptic transmission. This unique distribution makes it an attractive target for treating specific neurological conditions like tinnitus and essential tremor without the widespread sedative or amnestic side effects associated with non-selective GABAergic drugs. Research indicates that alpha 6-containing receptors are insensitive to classical benzodiazepines but can be modulated by specific compounds like DK-I-56-1, offering a pathway for precision pharmacology in sensory and motor disorders.
- Other names
- GABA(A) receptor subunit alpha-6GABA_A receptor alpha 6GABRA6Gamma-aminobutyric acid receptor subunit alpha-6
02
Mechanism of action
Positive allosteric modulation, Negative allosteric modulation, Antagonism
03
Biological functions
Inhibitory neurotransmissionTonic inhibitionChloride transportSynaptic transmissionRegulation of neuronal excitability
04
Disease associations
TinnitusEssential tremorMigraineTrigeminal neuralgiaNeuropsychiatric disordersAlcohol use disorder
05
Safety considerations
Motor coordination impairmentPotential for off-target effects on other GABA_A subunits (alpha 1-5)Limited expression profile (primarily cerebellar) may restrict systemic utility
06
Interacting drugs
DK-I-56-1
4 more in the full profile.
07
Biomarkers
GABRA6 mRNA expression in cerebellar granule cellsGABRA6 genetic polymorphisms (e.g., rs3219151)PET imaging using alpha-6 selective radioligands
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