To improve our understanding of the variant mechanistic effects underlying the HNF4A genotype-phenotype diversity, we hypothesized that this could be accomplished through investigations of the functional and structural consequences of seven variants located in the HNF-4A DBD and reported associated with either HNF4A-MODY, HNF4A-MODY and atypical Fanconi syndrome, or identified in rare T2D cases (Fig. 1 and Supplementary Table S1). This evidence concerns the gene HNF4A and type 2 diabetes mellitus.