TF and thalassemia: Many cases of such regulatory mutations have been studied, for example, the mutation (dbSNP ID rs281864518) in the promoter of the HBB gene next to the CCAAT motif, which affects the binding of C/EBP TF causing β+ thalassemia (12); the mutation (HGMD ID CR062116) in a nongenic region between the α-globin genes and their upstream regulatory elements, which creates a new binding site for GATA1 TF, leading to α thalassemia (11); and the mutation (dbSNP ID rs689466) upstream of the PTGS2 gene, which creates a c-MYB binding site and increases the risk of esophageal cancer (13).