We identified an AT/G mutation (rs386770867), comprising both an insertion and substitution at the same locus, positioned in the 5′-untranslated region (UTR) of SETDB2. We genotyped this variant in our family-based cohorts of asthma and then investigated its role in the regulation of SETDB2 using electrophoretic mobility shift assays (EMSAs), alleotyping and dual reporter gene assay analysis. The gene discussed is SETDB2; the disease is asthma.