Our findings here with respect to SETBP1 in non-diseased blood, suggest that GoF variants (already known to drive blood-associated cancers such as myeloid leukemia [16, 43, 49]) may impact SETBP1’s inactive TF role, suggesting future research directions that may shed light on the mechanism behind SETBP1-associated blood cancers. Here, SETBP1 is linked to cancer.