On the other hand, response of the C28X and K45X variants to geneticin treatment was prevented by sequence constraints of adjacent (C28, between pre- and pro-peptide; K45, between pro-peptide and mature FIX) cleavage sites essential for FIX processing, a finding in line with the severe/moderate hemophilia B associated with missense mutations at these positions [173,174,175]. The gene discussed is F9; the disease is hemophilia B.