Background: Wilson’s disease is a rare autosomal recessive genetic disorder of copper metabolism,
which is characterized by hepatic and neurological disease. ATP7B encodes a transmembrane
protein ATPase (ATP7B), which functions as a copper-dependent P-type ATPase. The mutations
in the gene ATP7B (on chromosome 13) lead to Wilson’s disease and is highly expressed in the liver,
kidney, and placenta. Consequently, this enzyme was considered a special topic in clinical and biotechnological
research. For in silico analysis, the 3D molecular modeling of this enzyme was conducted
in the I-TASSER web server.
Methods: For a better evaluation, the important characteristics of this enzyme such as the rare codons
of the ATP7B gene were evaluated by online software, including a rare codon calculator (RCC),
ATGme, LaTcOm, and Sherlocc program. Additionally, the multiple sequence alignment of this enzyme
was studied. Finally, for evaluation of the effects of rare codons, the 3D structure of ATP7B was
modeled in the Swiss Model and I-TASSER web server.
Results: The results showed that the ATP7B gene has 35 single rare codons for Arg. Additionally,
RCC detected two rare codons for Leu, 13 single rare codons for Ile and 28 rare codons for the Pro.
ATP7B gene analysis in minmax and sliding_window algorithm resulted in the identification of 16 and
17 rare codon clusters, respectively, indicating the different features of these algorithms in the detection
of RCCs. Analyzing the 3D model of ATP7B protein showed that Arg816 residue constitutes hydrogen
bonds with Glu810 and Glu816. Mutation of this residue to Ser816 cause these hydrogen bonds
not to be formed and may interfere in the proper folding of ATP7B protein. Furthermore, the side
chain of Arg1228 does not form any bond with other residues. By mutation of Arg1228 to Thr1228, a
new hydrogen bond is formed with the side chain of Arg1228. The addition and deletion of hydrogen
bonds alter the proper folding of ATP7B protein and interfere with the proper function of the ATP7B
position. On the other hand, His1069 forms the hydrogen bonds with the His880 and this hydrogen
bond adhere two regions of the protein together, which is critical in the final structural folding of
Conclusion: Previous studies show that synonymous and silent mutations have been linked to numerous
diseases. Given the importance of synonymous and silent mutations in diseases, the aim of this
study was to investigate the rare codons (synonymous codons) in the structure of ATP7B enzyme. By
these analyses, a new understanding was developed and our findings can further be used in some fields
of the clinical and industrial biotechnology.