Defects in OG:A repair in individuals with inheritedMUTYH variants are correlated with the colorectal cancer predispositionsyndrome known as MUTYH-associated polyposis (MAP).Herein, we reveal key structural features of OG required for efficientrepair by human MUTYH using structure–activity relationships(SAR). Here, MUTYH is linked to mutyh-associated polyposis.