A two-dimensional representation (top) of a GABAA receptor β3 subunit depicting binding loops (blue), coupling loops (pink) and four transmembrane regions (orange) is shown. Bar graph summarizing the fold-shift in GABA sensitivity (mean ΔlogEC50 ± s.d.) and maximum current (mean Imax ± s.d.) for each variant according to their amino acid residue. At GABA sensitivity, blue bars indicate variants that have significantly increased the GABA sensitivity with the direction of the bars upwards, red bars indicate variants that have significantly decreased the GABA sensitivity with the direction of the bars downwards and grey bars indicate no significant change. Significance was determined by one-way ANOVA (F (53, 725) = 355.5) and multiple comparisons with corrected Dunnett’s post-hoc test (p < 0.0001, n = 135 independent cells (wild-type); 10 (G32R, M80T, R142L, A305T, A305V, I306T); 11 (E77K, M80K, D120N, T157M, Y182F, Y184H, Q249K, S254F, L256Q, T281I, L284M, T287I, T288N, L293H, P301L); 12 (S76C, V78F, L124F, L170R, E180G, F225C, Y230H, Y245H, P253L, I280F, L284R, L284P, Y302C, F318S, N328D, E357K, S420I, R429Q, S433L); 13 (E178G, T185I); 14 (K127R, L165Q, Q210H, R232Q, T281A); 15 (V37G, N110D, ins138_139H, R166S, I300T); 17 (L310I). At maximum current, grey bars indicate no significant change and red bars indicate significantly reduced maximum currents. Significance was determined by one-way Kruskal–Willis ANOVA (H(55, 1653) = 674.4) and multiple comparisons with corrected Dunn’s post-hoc test (p < 0.0001, n = 256 independent cells (wild-type); 22 (R232P, L284R, I300T, Y302); 23 (D120N, L124F, L284, P301L, A305T); 24 (E77K, V78F, M80K, K127R, L165Q, Q210H, R232Q, Y245H, P253L, S254F, L256Q, I280F, T281A, T281I, L284M, T287I, T288N, L293H, A305V, I306T); 26 (M80T, Y184H, Q249K); 27 (G32R, S76C, R142L, L170R, E180G, Y182F); 28 (L310I); 29 (F318S, E357K, R429Q, S433L); 30 (ins138_139H, Q210H); 33 (V37G), p.(R166S); 36 (S420Ile); 39 (N328D). Individual data points are in the supplementary information (Supplementary Fig S2). Source data are provided in the Source Data file.