Prediction of Pathogenicity of rs۱۲۵۲۶۹۲۷۳۲ p.Gly۱۵۱Val missense mutation (rs۱۲۵۲۶۹۲۷۳۲) in MTTP Gene Associated with Abetalipoproteinemia by BioinformaticsTools

Abetalipoproteinemia typically presents in infancy with failure to thrive, diarrhea, vomiting,and malabsorption of fat. Hematologic manifestations may include acanthocytosis (irregularlyspiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia. .[۱]Abetalipoproteinemia is caused by a homozygous autosomal recessive mutation in the MTTP gene.More than ۳۳ mutations that cause the disease have been identified. This gene codes a microsomaltriglyceride protein (MTP) that mediates intracellular chylomicron or VLDL assembly and transport inthe intestinal mucosa and hepatocytes.[۲] Untreated individuals may develop spinocerebellardegeneration and retinitis pigmentosa. [۳] This study was conducted to find the pathogenicity impact ofan SNP in MTTP (rs۱۲۵۲۶۹۲۷۳۲). The MAF of this substitution by ClinVar was predicted to be۰.۰۰۰۰۱. A substitution at position p.Gly۱۵۱Val was predicted to affect protein function with a score of۰.۰۰ by SIFT, and this mutation is likely to be harmful with a score of ۱.۰۰۰ by Polyphen-۲. TheMetaRNN score of this type by Hope is ۰.۹۷۴۴۴۶۵. The mutant residue is larger than the wild-typeresidue and is more hydrophobic than the wild-type residue. Consequently, the mutation is located in adomain annotated in UniProt as deleterious. Then, this missense mutation can destroy performance andcan be pathogenic.

کلیدواژه ها:

Abetalipoproteinemia ، MTTP gene ، VLDL ، Bioinformatics