Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

•Combining CHD phenotype–driven gene set enrichment and CRISPR knockdown screening in zebrafish is an effective approach to identifying novel CHD genes.•Mutations affecting genes coding for the WAVE2 protein complex and small GTPase-mediated signaling are associated with LVOTO lesions.•WAVE2 complex genes brk1, nckap1, and wasf2 and regulators of small GTPase signaling cul3a and racgap1 are critical to zebrafish heart development.