There are a couple of examples from the 90s and 2000s when amino acid substitution in nucleic acid-binding protein abolished its function, e.g., an arginine to lysine substitution in the bZIP (Basic Leucine Zipper) domain of an opaque-2 mutant in maize abolished specific DNA-binding [59], missense mutations (Met175Arg and Ser191Asn) abolishing DNA-binding of the osteoblast-specific transcription factor OSF2/CBFA1 in human patients with cleidocranial dysplasia [60], or impaired RNA-binding of fragile X mental retardation protein upon missense mutation IIe-304→Asn in one of its KH domain [61]. The gene discussed is RUNX2; the disease is cleidocranial dysplasia 1.