Fig. 1: Genetic variation in UBE3A.
a The distribution of clinical interpretations in ClinVar for missense variants identified in UBE3A. Blue: Benign/Likely Benign, Red: Pathogenic/Likely Pathogenic, Gray: Uncertain/Conflicting. b Schematic showing human UBE3A with known functional domains. The number of variants and their positions corresponding to the UBE3A protein sequence are shown. c Cultured cells were transfected with increasing amounts of plasmid encoding WT UBE3A. Mean values are shown for Firefly/Renilla ratios ± standard error (SE). N = 3 independent experiments. d BAR responses of variants were normalized to WT UBE3A responses in each experiment. Values are shown as the mean ± SE. Each variant was tested in triplicate per experiment and the resulting values averaged. The number of experiments performed (n) and p-values calculated using a one-sample t-test (two-tailed) with Benjamini–Hochberg multiple comparisons correction (FDR = 0.05) are as follows: GFP, n = 19, ***p = 1.733 × 10−31; WT UBE3A, n = 19; UBE3A LD, ***p = 1.519 × 10−31, n = 19; R39H, n = 3, p = 0.567; A178T, n = 4, p = 0.828; T485A, n = 5, *p = 0.019; C21Y, n = 3, ***p = 8.725 × 10−6; C117R, n = 3, ***p = 3.419 × 10−4; N243K, n = 3, **p = 0.0072; E269G, n = 3, **p = 7.787 × 10−4; L273F, n = 3, **p = 0.0052; S349P, n = 3, **p = 0.0016; L502P, n = 3, **p = 0.0033; R506C, n = 3, **p = 0.0033; T106K, n = 6, **p = 0.0.0078; T106P, n = 3, **p = 0.0013; I130T, n = 6, *p = 0.016; R477P, n = 3, ***p = 4.24 × 10−4; M478I, n = 3, ***p = 3.39 × 10−4; R482P, n = 3, **p = 5.82 × 10−4; I329T, n = 5, ***p = 1.22 × 10−5; E550L, n = 3, *p = 0.0013.
