RNF43 is a tumor-suppressor gene and pathogenic variants (disease-causing) are associated with an increased risk for serrated polyposis syndrome (SPS), a condition characterized by multiple serrated polyps (precancerous) in the colon and an elevated lifetime risk for colorectal cancer. Most people with SPS do not have pathogenic variants in the RNF43 gene, so this is a rare cause of SPS. Management focuses on proactive colonoscopic surveillance, often beginning earlier and occurring more frequently than in the general population, with removal of all polyps large enough to pose cancer risk; some individuals may require closer follow-up depending on polyp burden and personal history. RNF43 pathogenic variants are not known to be more common in the Ashkenazi Jewish population.
SPS due to the RNF43 gene exhibits autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
