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Identification of Damaging ns SNV s in Human ERCC 2 Gene
Author(s) -
Fang Shuo,
Zhang Yuntong,
Xu Miao,
Xue Chunyu,
He Lin,
Cai Lei,
Xing Xin
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12772
Subject(s) - mutant , gene , biology , mutation , genetics , dna , microbiology and biotechnology , computational biology
The hERCC 2 gene is an important DNA repair molecule for initiating Cutaneous melanoma ( CM ). Therefore, it is advisable to study the possible functional SNV s in hERCC 2 . To achieve this goal, we collected total 2, 253 SNV s in hERCC 2 from the EMBL website, of which 303 are non‐synonymous single nucleotide variants (ns SNV s). Then, SIFT and PolyPhen were used to predict the damaging ns SNV s, and four ns SNV s (rs368866996, rs377739017, rs370819591, and rs121913022) were suggested to be damaging mutations. Since I‐Mutant2.0 showed a decrease in stability for the mutants containing each of the four ns SNV s, a 3D protein structure was modeled. Based on the comparison of the energy after minimization, RMSD and stabilizing residues between the native and mutant proteins' structure, rs121913022 was proposed to be the most damaging variant among the ns SNV s in hERCC 2 gene by decreasing the stability of protein. The mutant G713R of hERCC 2 protein caused by rs121913022 was found to have less expression level than native hERCC 2 protein in melanoma cells. These results suggest that rs121913022 may have potentially important clinical and drug target implications.