1.A.9.5.4
The GABA receptor consisting of α1, β3, and γ2 subunits.  Heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as the histamine receptor and mediates cellular responses to histamine. Functions as a receptor for diazepines and various anesthetics, such as pentobarbital which bind to separate allosteric effector binding sites. Functions as ligand-gated chloride channel (Jayakar et al. 2015).  GABRA1 mutations are associated with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, idiopathic familial generalized epilepsy, infantile spasms and  Dravet syndrome. Thus, GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies including Ohtahara syndrome and West syndrome (Kodera et al. 2016). A variant of GABRA1 (A332V) causes increased sensitivity for GABA and alterred desensitization (Steudle et al. 2020). Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (Johannesen et al. 2021). The patho-mechanism and precision medicine approach in GABRA1-related disorders have been discussed (Musto et al. 2023). Receptor desensitization of gain-of-function GABRB3 variants correlates with clinical severity (Lin et al. 2023). GABRG2 mutations cause genetic epilepsy with febrile seizures: the structures. The roles, and molecular genetics have been described (Li et al. 2024).