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Updated: Jun 27, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
Published on: June 6, 2025
The human GABA A receptor α4 subunit variant Ile114Asn linked to epilepsy impairs membrane expression with β3 and δ
Draegan A Watson1, Cecilia M Borghese1, Kristina Jülich2
1Department of Neuroscience, The University of Texas at Austin, Austin, USA.
Abstract:
GABA A receptors mediate fast inhibitory neurotransmission in the brain, and variants in their subunits are linked to neurological disorders like epilepsy. For many identified variants, it remains to be determined whether the variant is pathogenic. Here, we functionally characterized the α4 subunit variant p.I114N (p.I79N in the mature protein), found in an individual with epilepsy, using patch-clamp electrophysiology in combination with β3 and δ subunits in HEK293T cells. Whereas the variant has little to no impact on basal activity or GABA-sensitivity, lower maximal GABA-elicited currents as compared to wild-type channels suggest that it impairs assembly or trafficking to reduce expression of channels in the plasma membrane.
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