RNF43 Gene Mutations

Serrated Polyposis Syndrome (SPS)




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Additional Information

RNF43 gene

Associated Syndrome Name: Serrated Polyposis Syndrome (SPS)

RNF43 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
ColorectalElevated Risk

RNF43 gene Overview

Serrated Polyposis Syndrome (SPS) 1, 2, 3, 4, 5, 6
  • Mutations in RNF43 have been found in some individuals with a clinical diagnosis of Serrated Polyposis Syndrome (SPS).
  • Individuals with SPS develop multiple and/or large polyps in the colon and rectum. These can be hyperplastic polyps, serrated polyps, or sessile serrated adenomas. The World Health Organization (WHO) has developed detailed criteria for a clinical diagnosis of SPS (see Guarinos C et al., World J Gastroenterol. 2012 18:2452-61).
  • Individuals with SPS are believed to have a significantly increased risk for colorectal cancer. The exact size of this risk is not known, and it is not known if this risk is present in individuals with mutations in RNF43 who do not have a clinical diagnosis of SPS.
  • Although there may be an increased risk for colorectal cancer in individuals with mutations in RNF43, it may be possible to reduce this risk with appropriate medical management. Since information about the cancer risks associated with RNF43 mutations is relatively new, and there is uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics professionals who have expertise in this emerging area of knowledge.

RNF43 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
ColorectalTo age 801, 4, 5, 7Elevated risk3.0%

RNF43 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
ColorectalRNF43 mutation carriers who do meet WHO criteria for a diagnosis of SPS should be managed based on guidelines from NCCN and other professional societies. These guidelines include recommendations for frequent colonoscopy screenings, beginning at young ages, and surgical evaluation based on family history and personal polyp history.3, 8When identified as meeting WHO criteria for SPSNA
Currently there are no specific management guidelines for colorectal cancer risk in RNF43 mutation carriers who do not meet WHO criteria for a diagnosis of SPS. However, the possibility of an increased risk for colorectal cancer warrants consideration of individualized colorectal cancer risk-reduction strategies, such as the modification of standard population screening recommendations by starting screening at younger ages and/or performing screening more frequently.9NANA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the RNF43 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.


  1. Yan HHN, et al. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. Gut. 2017 66:1645-1656. PMID: 27329244.
  2. Gala MK, et al.Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas. Gastroenterology. 2014 146:520-9. PMID: 24512911.
  3. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 3.2019. Dec 13. Available at http://www.nccn.org.
  4. Buchanan DD, et al. Genetics of Colonic Polyposis Study. Lack of evidence for germline RNF43 mutations in patients with serrated polyposis syndrome from a large multinational study. Gut. 2017 66:1170-1172. PMID: 27582512.
  5. Guarinos C, et al. Serrated polyposis syndrome: molecular, pathological and clinical aspects. World J Gastroenterol. 2012 18:2452-61. PMID: 22654442.
  6. Taupin D, et al. A deleterious RNF43 germline mutation in a severely affected serrated polyposis kindred. Hum Genome Var. 2015 2:15013. PMID: 27081527.
  7. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
  8. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
  9. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2019. Aug 2. Available at http://www.nccn.org.
Last Updated on 10-Dec-2020