The significance of this gene as a locus for vasculopathy susceptibility was first demonstrated in 2011 through genome-wide linkage analysis in a cohort of Japanese families with moyamoya disease, where heterozygosity for the RNF213 p.Arg4810Lys (c.14429G > A, rs112735431) polymorphism was significantly associated with the disease [81]. Here, RNF213 is linked to vascular disorder.