PKLR and hemophilia B: Variation in cis sequences can interfere cis-trans interaction and therefore modulate gene expression in physiological condition; mutation in cis sequences can cause abnormal gene expression contributing to pathological consequences [11–16], such as the mutation in factor IX core promoter in hemophilia B and Hemophilia B Leyden [17, 18], and the mutation in PKLR promoter in pyruvate kinase (PK)-deficient anemia [19].