Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study

Abstract

RRM2B gene encodes ribonucleoside-diphosphate reductase subunit M2 B, the p53-inducible small subunit (p53R2) of ribonucleotide reductase (RNR), an enzyme catalyzing dNTP synthesis for mitochondrial DNA. Defects in this gene may cause severe mitochondrial disease affecting mainly the nervous system. This study is aimed at examining the effect of deleterious nonsynonymous SNP (nsSNP) on the structure of the RRM2B protein, using a variety of prediction tools followed by a molecular modeling analysis. After using 13 algorithms, 19 nsSNPs were predicted deleterious. Among these variants, 18 decreased the protein stability and 16 were localized in very highly conserved regions. Protein 3D structure analysis showed that 18 variants changed amino acid interactions. These results concur with what has been found in experimental trials; 7 deleterious nsSNPs were previously reported in patients suffering from genetic disorders affecting the nervous system. Thus, our study will provide useful information to design more efficient and fast genetic tests to find RRM2B gene mutations.

Discovery of DNA polymorphisms via whole genome resequencing and their functional relevance in salinity stress response in chickpea

“…The structural integrity of encoded proteins can be affected due to non‐synonymous SNPs present within the coding regions of genes (Ait El Cadi et al, 2020; Saleh et al, 2016). We identified three salinity tolerance QTL‐associated genes ( Ca_12482 , Ca_12486 , and Ca_12493 ) that harbor non‐synonymous SNPs.…”

Genome‐wide discovery ofDNApolymorphisms via resequencing of chickpea cultivars with contrasting response to drought stress

“…The DNA polymorphisms located in promoter regions may govern the gene expression via altering the affinity/binding of the TFs to their respective cis ‐regulatory motifs (Johnston et al, 2019). Likewise, the DNA polymorphisms in the coding regions may disrupt the stability/integrity of the encoded proteins (Ait El Cadi et al, 2020; Saleh et al, 2016). We found 10% and 13% of the SNPs and InDels, respectively, located in the promoter regions, whereas only 3% and 1% of the SNPs and InDels, respectively, were located in the coding regions (Figure 2A,B).…”

“…The nonsynonymous SNPs located in the coding region may affect the structural integrity and stability of the encoded proteins (Ait El Cadi et al, 2020; Saleh et al, 2016). Three abiotic stress‐related genes ( Ca_00700 , Ca_05322 , and Ca_13077 ) were found to harbor nonsynonymous SNP(s).…”

Computational and Mass Spectrometry-Based Approach Identify Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) in JMJD6

“…In recent years, a lot of software has been developed to predict deleterious nsSNPs through different algorithms and biological considerations, which is cost-effective and fast. At present, we integrated software for predicting damaging nsSNPs SIFT, PANTHER, and SNAP and software for inferring that the damaging effects of disease-related nsSNPs PhD-SNP, PolyPhen-2, SNPS&GO, and I-Mutant 2.0 are relatively mature, which has been widely employed in several previous studies [ 18 , 33 , 34 , 35 , 36 ]. The rationales of the prediction and inference of deleterious nsSNPs rely on considerations of the protein domain and sequence conservation.…”