title: In silico analysis of the deleterious nsSNPs (missense) in the homeobox domain of human HOXB13 gene responsible for hereditary prostate cancer.
abstract: The human HOXB13 gene encodes a transcription factor containing a DNA-binding homeobox domain and a HoxA13 N-terminal domain. SNP is considered to be the primary genetic cause for hereditary prostate cancer (PCa). The study of functional nsSNPs would give an insight into the exact cause underlying the onset of hereditary PCa and possible methodologies for the cure or early management of the disease. Several in silico tools were used to screen and map the deleterious nsSNPs to the protein structure for predicting the structure-function effects. Among the 23 homeobox nsSNPs, sift predicted 20, whereas PolyPhen, panther, and provean predicted 21 nsSNP's as deleterious. W63R, D244N, K239Q, P222R, K218R, and G216C were found to have higher energy values than the native 2CRA. The RMSD value showed increased deviation for T253P(2.53 Å), P222R(2.27 Å), G216C(2.15 Å), K218R(1.66 Å), and K239Q(1.62 Å). The I-Mutant showed increase in the stability of R258C, S254T, S250L, K239Q, and Q227E. Ramachandran plot showed mutants P222R, G216C, W263R, and K218R having drastically unfavorable pattern of amino acid residues. The presence of these mutations may result in the altered structure and function of the transcription factor; however, the exact mechanism and pathology of those predicted nsSNPs should further be validated by in vivo experiments and population-based studies.
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Chandrasekaran
authors.affiliation: Department of Urology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Eu Chang
authors.initials: EC
authors.lastname: Hwang
authors.affiliation: Department of Urology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Taek Won
authors.initials: TW
authors.lastname: Kang
authors.affiliation: Department of Urology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Dong Deuk
authors.initials: DD
authors.lastname: Kwon
authors.affiliation: Department of Urology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Kwangsung
authors.initials: K
authors.lastname: Park
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Vinoth-Kumar
authors.identifier: 0000-0002-7420-8459
authors.initials: VK
authors.lastname: Lakshmanan
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins
keywords: HOXB13; hereditary prostate cancer; homeobox domain; non-synonymous SNPs; single-nucleotide polymorphism