While cancer-associated mutations in genes encoding RAD21, SMC3, and STAG1 are always heterozygous (Thota et al., 2014; Kon et al., 2013; Tsai et al., 2017), mutations in the X chromosome-located genes SMC1A and STAG2 can result in complete loss of function due to hemizygosity (males), or silencing of the wild type during X-inactivation (females). Here, STAG2 is linked to cancer.