These mutations are loss-of-function, frequently truncating mutations; the Japan study identified high dN/dS ratios for PIGR, NFKBIZ, ZC3H12A, the IL-17 receptor IL17RA, as well as the tumor suppressor ARID1A, suggesting functional selection in non-dysplastic IBD colon [25]. This evidence concerns the gene NFKBIZ and inflammatory bowel disease.