Residues lining this pocket are well conserved in the T-box family and have been shown to be important in vivo as clusters of point mutations from several different human genetic diseases map to this site (Fig. 4d), and mutational analysis in the murine T-bet protein indicates critical roles for this pocket in interactions with permissive chromatin re-modelers including KDM6A and KDM6B34. This evidence concerns the gene KDM6A and hereditary disease.