biostudies-literaturePeng YNIGMS NIH HHS27270-87https://www.ebi.ac.uk/biostudies/studies/S-EPMC4661880biostudies-literatureUnknown16(11)Mutations in KDM5C gene are linked to X-linked mental retardation, the syndromic Claes-Jensen-type disease. This study focuses on non-synonymous mutations in the KDM5C ARID domain and evaluates the effects of two disease-associated missense mutations (A77T and D87G) and three not-yet-classified missense mutations (R108W, N142S, and R179H). We predict the ARID domain's folding and binding free energy changes due to mutations, and also study the effects of mutations on protein dynamics. Our computational results indicate that A77T and D87G mutants have minimal effect on the KDM5C ARID domain stability and DNA binding. In parallel, the change in the free energy unfolding caused by the mutants A77T and D87G were experimentally measured by urea-induced unfolding experiments and were shown to beInternational journal of molecular sciencesMutations in the KDM5C ARID Domain and Their Plausible Association with Syndromic Claes-Jensen-Type Disease.PMC46618805P20GM103444-07P20 GM103444R01 GM093937R01GM093937Peng YYang YCao WSuryadi JKucukkal TGAlexov EfalseMutations in the KDM5C ARID Domain and Their Plausible Association with Syndromic Claes-Jensen-Type Disease.Mutations in KDM5C gene are linked to X-linked mental retardation, the syndromic Claes-Jensen-type disease. This study focuses on non-synonymous mutations in the KDM5C ARID domain and evaluates the effects of two disease-associated missense mutations (A77T and D87G) and three not-yet-classified missense mutations (R108W, N142S, and R179H). We predict the ARID domain's folding and binding free energy changes due to mutations, and also study the effects of mutations on protein dynamics. Our computational results indicate that A77T and D87G mutants have minimal effect on the KDM5C ARID domain stability and DNA binding. In parallel, the change in the free energy unfolding caused by the mutants A77T and D87G were experimentally measured by urea-induced unfolding experiments and were shown to be2015-01-01T00:00:00Z2015 Nov2026-05-05T08:18:29.175Z2019-03-27T02:02:51ZS-EPMC46618802658060310.3390/ijms161126022