Results in Chemistry (Dec 2023)

Identification of rare nsSNPs in fragile histidine triad (FHIT) gene to explore its correlation with oral cancer: An in-silico approach

  • Shreyans Sadangi,
  • Apurva Mandhane,
  • Amrita Kumari Panda,
  • Govinda Kapusetti,
  • Santosh Kumar Behera,
  • Sanghamitra Pati

Journal volume & issue
Vol. 6
p. 101072

Abstract

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Genetic alterations in fragile histidine triad (FHIT) play a pivotal role in various cancers of head, neck, lung, kidney, gastrointestinal, and breast including oral which leads to abnormal transcripts in vivo during the development of oral cancer. Owing to the importance of FHIT gene in cell proliferation, tumor suppression and survival, the structural, functional, non-synonymous SNPs (nsSNPs), and network study was conducted to look at the potential relationship between phenotypic variations and genetic variations. In silico genomic analysis of FHIT was initiated with the identification of 18 rare variants from dbSNP database followed by PredictSNP 1.0 web server analysis for predicting the deleterious and neutral mutants. A total of 11 mutations i.e. P33T, P33A, V97F, S22A, T19I, T61M, D57N, P101A, P101S, S81P and R46H corresponding to 9 nsSNPs were found to be deleterious which affects the protein. The interacting genes with FHIT were found by analyzing protein–protein interactions network using a STRING database. Gene ontology and Disease Association functional analysis of FHIT was obtained by WebGestalt. The mutational positions and amino acid variations have been mapped onto native FHIT. Structural and docking analysis of native and mutant FHIT with ER 27319 Maleate was performed using Auto Dock 4.2, GLIDE, SRide server, structural visualizers, and MD simulations to check their binding energies, stabilizing residues, and to investigate their dynamic behavior, mode of binding action and inhibitor specificity. Our in-silico analysis suggested that screening of P101S (rs533270218), S81P (rs536941406) and D57N (rs375883257) variants of FHIT could be useful for molecular diagnosis and development of vital molecular inhibitors of FHIT pathways. The diagnostic and prognostic approach of these molecular biomarkers can intrude on the predisposition to oral cancer.

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