Our analysis now indicates a direct genetic interaction between two IBD susceptibility genes namely, HNF4A and RNF186. While a singular loss-of-function mutation in HNF4A has already been shown to be associated with susceptibility to abnormal intestinal permeability, inflammation and oxidative stress, we speculate that a dual loss-of-function with additional mutation in RNF186 would further exacerbate one's susceptibility to develop chronic inflammation in the gut [29], [30]. The gene discussed is RNF186; the disease is inflammatory bowel disease.