Fig. 2: Functional evaluation of GABRB3 missense variants. | Nature Communications

Fig. 2: Functional evaluation of GABRB3 missense variants.

From: Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies

Fig. 2

a Concatenated receptor design showing the γ2-β3-α1-β3-α1 DNA construct used to introduce single missense variants. A pentameric receptor that arranges with a single β3 variant (star) is depicted. b Raw electrophysiological recordings and concentration–response curves at selected concatenated γ2-β3-α1-β3-α1 wild-type (black), p.(Leu284Pro) (blue) and p.(Tyr302Cys) (red) β3 variant receptors that represent a gain-of-function and a loss-of-function variant, respectively. Bars indicate GABA applications and scale bars for each trace are shown. Peak current amplitudes were measured at each GABA concentration and a Hill equation was fitted to the data. Thereafter the dataset was normalized to its respective maximum current amplitude for each cell. Black circles (wild-type, n = 12 independent cells), blue open squares (p.(Leu284Pro), n = 12) and red open circles (p.(Tyr302Cys), n = 12) represent the mean ± s.d (n ≥ 12) and the lines represent the fitted Hill equation at each receptor. Gain-of-function variants shift the concentration–response curve to the left, loss-of-function to the right. Source data are provided in the Source Data file.

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