title: Identification of Damaging nsSNVs in HumanERCC2 Gene.
abstract: The hERCC2 gene is an important DNA repair molecule for initiating Cutaneous melanoma (CM). Therefore, it is advisable to study the possible functional SNVs in hERCC2. To achieve this goal, we collected total 2, 253 SNVs in hERCC2from the EMBL website, of which 303 are non-synonymous single nucleotide variants (nsSNVs). Then, SIFT and PolyPhen were used to predict the damaging nsSNVs, and four nsSNVs (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 nsSNVs, 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 nsSNVs in hERCC2 gene by decreasing the stability of protein. The mutant G713R of hERCC2 protein caused by rs121913022 was found to have less expression level than native hERCC2 protein in melanoma cells. These results suggest that rs121913022 may have potentially important clinical and drug target implications.
authors.affiliation: Department of Plastic and Reconstruction, Shanghai Changhai Hospital Affiliated to Second Military Medical University, Shanghai, 200433, China.|Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Bio-X Institutes, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Orthopedics, Shanghai Changhai Hospital Affiliated to Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yuntong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstruction Surgery, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, 200092, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Plastic and Reconstruction, Shanghai Changhai Hospital Affiliated to Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Xue
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Bio-X Institutes, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Bio-X Institutes, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Plastic and Reconstruction, Shanghai Changhai Hospital Affiliated to Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xing
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: cutaneous melanoma; hERCC2; nsSNV