In summary, our findings suggest that the CR inserted at chr17q24.3 causes the skeletal Class II malocclusion with gingival hyperplasia in the family, and that the most probable pathogenic mechanism underlying the abnormal phenotype involves KCNJ2/KCNJ16 misregulation induced by neo-TAD formation and adopted craniofacial enhancers. Here, KCNJ16 is linked to gingival disorder.