We further presented two mechanisms through which chronic diarrhea-risk-associated variant at 7q31.1 lead to increased dysfunction of the epithelial barrier by lower levels and activity of SLC26A3: (a) P131R-SLC26A3 reduced SLC26A3 expression through an enhanced ubiquitination mediated degradation pathway, and (b) a disrupted interaction with ZO-1/CFTR protein (Fig. 5), resulting in increased epithelial permeability and induced epithelial barrier dysfunction. This evidence concerns the gene CFTR and chronic diarrheal disease.