A computational analysis reveals eight novel high-risk single nucleotide variants of human tumor suppressor LHPP gene

Abstract Background LHPP is a tumor suppressor protein associated with various malignancies like liver, oral, pharyngeal, bladder, cervical, and gastric cancers through controlling pathways. Several single nucleotide variants have been reported to cause cancers. The main objectives of our study were investigate the impact deleterious non-synonymous on structure functions protein. Results We used nine computational tools (SNAP2, PROVEAN, POLYPHEN 2, PREDICT SNP, MAPP, PhD-SNP, SIFT, PANTHER, PMUT) find out SNPs. These algorithms predicted 34 nsSNPs be as result their analysis. Using ConSurf, I-Mutant, SDM, MUpro, Mutpred, we emphasized more how those harmful negatively affect function Furthermore, mutant structures assessed total energy value deviation in comparison original also calculated RMSD values TM scores. By comparing from all these approaches, shortlisted eight novel (D214G, D219N, Q224P, L231P, G236W, R234C, R234P, V233G) that impose high risks To analyze protein’s behavior physiological condition, performed 50 ns molecular dynamic simulation using WebGro online tool found mutants vary wild type terms RMSD, RMSF, Rg, SASA, H-bond numbers. Prognostic significance analysis by Kaplan–Meier plotter showed abnormal regulation can serve prognostic marker for patient breast, ovarian, Additionally, ligand binding sites revealed presence D214G D219N site one which means two disturb capacity Protein–protein interaction proteins’ interactions PPA1, ATP12A, ATP4A, ATP4B, ATP5F1, ATP5J, PPA2, ATP6V0A4, ATP6V0A2, MT-ATP8 different degree connectivity. Conclusion results demonstrate understanding effect LHPP, may useful approaches.