The interactions of proteins with nucleic acids are important for various cellular mechanisms and these interactions are responsible for replication, transcription, and translation. The substitution of amino acid residues in the interfaces of protein nucleic-acid complexes (protein-DNA and protein-RNA) alter the stability, binding affinity, function and leading to various diseases. Identifying the disease-causing mutations are important to understand the molecular basis of diseases and development of therapeutic strategies. In this seminar, I will present the role of nucleic-acid binding proteins in disease development and effect of mutations on protein-nucleic acid interactions. In addition, I will discuss the relationship of sequence and structure-based parameters with disease causing mutations in nucleic acid binding proteins. Further, distribution of mutations in protein-interfaces, and DNA binding domain will be discussed. Preliminary results obtained will be highlighted.