Pathogenicity prediction of a single nucleotide polymorphism (rs۱۰۴۸۹۴۱۰۷: p.G۱۳۰V) in human FXN gene

Friedreich's Ataxia (FRDA or FA) is an autosomal recessive disorder that causes difficultyin walking, impaired speech, and loss of arm and leg coordination. This condition is caused by amutation in the FXN gene on chromosome ۹ which produces a protein called Frataxin. In FRDA, cellsproduce less Frataxin which leads to degeneration of nerve tissue in the spinal cord and ataxia. In thisstudy, we have investigated the pathogenicity of one type of SNP, rs۱۰۴۸۹۴۱۰۷ (p.G۱۳۰V), in thisdisease. rs۱۰۴۸۹۴۱۰۷ affected the protein function with a score of ۰.۰۰ by the SIFT and was predictedto be possibly damaging with a score of ۱.۰۰۰ by the PolyPhen-۲ programs. Also, it was checked by IMutant,showing a large decrease in its stability with a DDG value of approximately -۱.۶۹. Moreover,the HOPE server indicated that the interaction between domains could be disturbed by the mutation,which might affect protein function and the signal transduction between the domains. the wild-typeresidue (p.G۱۳۰) is the most flexible of all residues. Mutation of this glycine can abolish this function.While the wild-type residue (p.G۱۳۰) was buried in the core of the protein, the mutant residue (p.V۱۳۰)is bigger and probably will not fit. The torsion angles for this residue are unusual. Only glycine isflexible enough to make these torsion angles. In conclusion, this study suggested that the SNP variantof FXN would have an effect on the protein function and could be pathogenic and damage protein.

کلیدواژه ها:

Friedreich's Ataxia (FRDA or FA) ، FXN gene ، SNP ، Missense mutation