Screening of Pathogenic Missense Single Nucleotide Variants From Gene Associated With the Hepatocellular Carcinoma: An Approach

LHPP gene encodes a phospholysine phosphohistidine inorganic pyrophosphate phosphatase, which functions as a tumor-suppressor protein. The tumor suppression by this protein has been confirmed in various cancers, including hepatocellular carcinoma (HCC). LHPP downregulation promotes cell growth and p...

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Bibliographic Details
Published in:Bioinformatics and biology insights 2022-08, Vol.16
Main Authors: Malik Siddique Mahmood, Maryam Afzal, Hina Batool, Amara Saif, Tahreem Aqdas, Naeem Mahmood Ashraf, Mahjabeen Saleem
Format: Article
Language:English
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Summary:LHPP gene encodes a phospholysine phosphohistidine inorganic pyrophosphate phosphatase, which functions as a tumor-suppressor protein. The tumor suppression by this protein has been confirmed in various cancers, including hepatocellular carcinoma (HCC). LHPP downregulation promotes cell growth and proliferation by modulating the PI3K/AKT signaling pathway. This study identifies potentially deleterious missense single nucleotide variants (SNVs) associated with the LHPP gene using multiple computational tools based on different algorithms. A total of 4 destabilizing mutants are identified as L22P, I212T, G227R , and G236R , from the conserved region of the phosphatase. The 3-dimensional (3D) modeling and structural comparison of variants with the native protein reveals significant structural and conformational variations after mutations, suggesting disruption in the function of phospholysine phosphohistidine inorganic pyrophosphate phosphatase. The identified mutations might, therefore, participate in the cause of HCC.
ISSN:1177-9322
DOI:10.1177/11779322221115547