insilico evaluation of rare codons and their positions in the structure of atp8b1 gene

Background: progressive familial intrahepatic cholestases (pfic) are a spectrumof autosomal progressive liver diseases developing to end-stage liver disease.atp8b1 deficiency caused by mutations in atp8b1 gene encoding a p-type atpaseleads to pfic1. the gene for pfic1 has been mapped on a 19-cm region of 18q21-q22, and a gene defect in atp8b1 can cause deregulations in bile salt transportersthrough decreased expression and/or activity of fxr. point mutations are the mostcommon, with the majority being missense or nonsense mutations. in addition, approximately15% of disease-causing atp8b1 mutations are annotated as splicingdisrupting alteration given that they are located at exon-intron borders.objective: here, we describe the hidden layer of computational biology informationof rare codons in atp8b1, which can help us for drug design.methods: some rare codons in different locations of atp8b1 gene were identifiedusing several web servers and by in-silico modelling of atp8b1 in phyre2 andi-tasser server, some rare codons were evaluated.results: some of these rare codons were located at special positions which seemto have a critical role in proper folding of atp8b1 protein. structural analysis showedthat some of rare codons are related to mutations in atp8b1 that are responsible forpfic1 disease, which may have a critical role in ensuring the correct folding.conclusion: investigation of such hidden information can enhance our understandingof atp8b1 folding. moreover, studies of these rare codons help us to clarifytheir role in rational design of new and effective drugs.