EHD2 and cancer: To systematically characterize the ARID1B EHD2 domain structure–function relationship, we performed deep mutational scanning (DMS) with two functional assays: (1) a cellular proliferation assay in which expression of ectopic ARID1B cDNA rescues the lethal phenotype induced by silencing endogenous ARID1B in an ARID1A mutant cancer cell line, (2) a sensor assay for protein stability and/or abundance using a bicistronic vector expressing green fluorescent protein (GFP)-tagged ARID1B EHD2 domain and a mCherry protein to normalize expression levels (Fig. 1b) similar to VAMP-seq10.