In-silico Evaluation of Rare Codons and their Positions in the Structure of ATP۸b۱ Gene

Background: Progressive familial intrahepatic cholestases (PFIC) are a spectrum of autosomal progressive liver diseases developing to end-stage liver disease. ATP۸B۱ deficiency caused by mutations in ATP۸B۱ gene encoding a P-type ATPase leads to PFIC۱. The gene for PFIC۱ has been mapped on a ۱۹-cM region of ۱۸q۲۱-q۲۲, and a gene defect in ATP۸B۱ can cause deregulations in bile salt transporters through decreased expression and/or activity of FXR. Point mutations are the most common, with the majority being missense or nonsense mutations. In addition, approximately ۱۵% of disease-causing ATP۸B۱ mutations are annotated as splicing disrupting alteration given that they are located at exon-intron borders. Objective: Here, we describe the hidden layer of computational biology information of rare codons in ATP۸B۱, which can help us for drug design. Methods: Some rare codons in different locations of ATP۸b۱ gene were identified using several web servers and by in-silico modelling of ATP۸b۱ in Phyre۲ and I-TASSER server, some rare codons were evaluated. Results: Some of these rare codons were located at special positions which seem to have a critical role in proper folding of ATP۸b۱ protein. Structural analysis showed that some of rare codons are related to mutations in ATP۸B۱ that are responsible for PFIC۱ disease, which may have a critical role in ensuring the correct folding. Conclusion: Investigation of such hidden information can enhance our understanding of ATP۸b۱ folding. Moreover, studies of these rare codons help us to clarify their role in rational design of new and effective drugs.

Keywords:

Progressive Familial Intrahepatic Cholestasis , Bioinformatics analysis , ATP۸b۱ , Rare codon