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Structure analysis of deleterious nsSNPs in human PALB2 protein for functional inference


Noshin Nawar, Anik Paul, Hamida Nooreen Mahmud, AR-Rafi Md. Faisal, Md. Ismail Hosen, Hossain Uddin Shekhar*



Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka,Bangladesh; Corresponding author*



Dr. Hossain Uddin Shekhar - E-mail: hossainshekhar@du.ac.bd


Article Type

Research Article



Received February 28, 2021; Revised March 15, 2021; Accepted March 18, 2021, Published March 31, 2021



Partner and Localizer of BRCA2 or PALB2 is a typical tumor suppressor protein, that responds to DNA double stranded breaks through homologous recombination repair. Heterozygous mutations in PALB2 are known to contribute to the susceptibility of breast and ovarian cancer. However, there is no comprehensive study characterizing the structural and functional impacts of SNPs located in the PALB2 gene.Therefore, it is of interest to document a comprehensive analysis of coding and non-coding SNPs located at the PALB2 loci using in silico tools. The data for 1455 non-synonymous SNPs (nsSNPs) located in the PALB2 loci were retrieved from the dbSNP database. Comprehensive characterization of the SNPs using a combination of in silico tools such as SIFT, PROVEAN, PolyPhen, PANTHER, PhDSNP, Pmut, MutPred 2.0 and SNAP-2, identified 28 functionally important SNPs. Among these, 16 nsSNPs were further selected for structural analysis using conservation profile and protein stability. The most deleterious nsSNPs were documented within the WD40 domain of PALB2. A general outline of the structural consequences of each variant was developed using the HOPE project data. These 16 mutant structures were further modelled using SWISS Model and three most damaging mutant models (rs78179744, rs180177123 and rs45525135) were identified. The non-coding SNPs in the 3 UTR region of the PALB2 gene were analyzed for altered miRNA target sites. The comprehensive characterization of the coding and non-coding SNPs in the PALB2 locus has provided a list of damaging SNPs with potential disease association. Further validation through genetic association study will reveal their clinical significance.



PALB2, nsSNP, UTR, in silico characterization.



Nawar et al. Bioinformation 17(3): 424-438 (2021)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.