Fig. 1.

Disruption of protein interaction helps identify important de novo missense (dnMis) variants in ASD probands. a Data source of dnMis variants and a schematic diagram showing the proteome-wide mapping of dnMis variants onto protein–protein interaction interfaces for predicting interaction disruption. b Interaction disruptions are more common in ASD probands than in unaffected siblings. c Interaction disruption predictions rescue disruptive dnMis variants that were not recognized as damaging by MPC. Left: a Venn diagram showing the logical relations between genes affected by disruptive dnMis variants predicted by interaction disruption (red) and by MPC (Missense badness, PolyPhen-2, and Constraint; solid blue: MPC ≥ 2; dashed blue: MPC ≥ 1). Right: a co-crystal structure of ADAP1-KIF13B (PDB ID: 3MDB) displaying the interface location of an ASD proband dnMis variant ADAP1 G144R