In-silico Pathogenicity Analysis ofp.Pro۳Leu Missense Mutation (rs۱۱۷۱۰۳۶۴۰۶) in HESE۵

Background: Hes۵ (Hes Family BHLH Transcription Factor۵) gene encodes a member of a family of basic helix-loop-helixtranscriptional repressors. The protein product of this gene,which is activated downstream of the Notch pathway, regulatescell differentiation in multiple tissues. Disruptions in the normalexpression of this gene have been associated with variousdevelopmental diseases and cancer. Acute lymphoblastic leukemia(ALL) is a type of blood cancers that starts from whiteblood cells called lymphocytes in the bone marrow. Adults and children can get it but it is most often diagnosed in youngerpeople. Previous studies identified several genomic changesin HES family genes involved in development of B cell acutelymphoblastic leukemia (B ALL).Materials and Methods: In Hes۵ gene, amino acid prolinereplace with leucine in position ۳ (p.Pro۳Leu: rs۱۱۷۱۰۳۶۴۰۶).The mutation type leads to disease-related polymorphism (Poly-Phen: probably damaging: ۰.۹۹۴, SIFT: deleterious: ۰). Eachamino acid has its own specific features like size and hydrophobicityvalue for example leucine is more hydrophilic thanproline (hydrophobicity score for leucine is -۳.۹۰۰ and for prolineis -۱.۶۰۰). The mutant residue is bigger that the wild type.Proline is very rigid and, therefore, induces a special backboneconformation which might be required at this position.Results: The missense mutation can disturb ۳-D conformationand changes a proline with an important function into leucine,thereby disturbing the local structure. The mutant and wild-typeresidues are not very similar. Based on this prediction informationthis missense mutation is probably damaging to the HES۵protein because located near a highly conserved position.

کلیدواژه ها:

Hes۵ ، Transcriptional repressor ، BHLH ، Leukemia ، bloodcancer