Predicting the pathogenicity of a missense mutation (Glu۸۸Lys) in the NCAPG gene involved in childhood hepatocellular carcinoma using bioinformatics tools

Pediatric hepatocellular carcinoma (HCC) is a rare and malignant liver tumor in childrenwith a poor prognosis. This development is mainly observed in children over ۱۰ years old, whether theyhave a cirrhotic or non-cirrhotic background. NCAPG, a protein associated with chromosomalcondensation during mitosis, ensures the correct separation of sister chromatids during chromosomecondensation and fusion. It also plays a role in condensing and stabilizing chromosomes during bothmeiosis and mitosis. NCAPG has been demonstrated to be highly expressed in various cancers, and itsrelated molecular mechanism impacts tumor cell proliferation, invasion, metastasis, and apoptosis suchas hepatocellular carcinoma, gastric cancer, colorectal cancer, ovarian cancer, lung adenocarcinoma,breast cancer and prostate cancer. Moreover, the sensitivity of tumor cells can be decreased by NCAPGto reduce the reaction to the original chemotherapy, leading to drug-resistant tumor cells. To sum up,NCAPG is capable of being a new diagnosis and treatment target for several cancers and is also a verypromising prognostic marker. Our objective is to assess the pathogenesis of a missense mutation inNCAPG. As a result of this mutation, the glutamic acid at position ۸۸ turns into lysine amino acid.Several bioinformatics tools, including polyphen-۲, I-Mutant ۲.۰, and SIFT; have been utilized toanalyze this assessment. Polyphen-۲ analysis confirmed the possible harm caused by this mutation, witha score of ۰.۹۱۷ in the HumDiv model. This missense mutation has been proven by I-Mutant to decreasethe stability of NCAPG. The SIFT scored ۰.۰۰ for the protein function affected by the mutation atposition ۸۸ NCAPG.According to this analysis, the substitution of glutamic acid with lysine in position ۸۸ may result inpathological effects for the NCAPG protein. The score of pathogenicity of this SNP is very high, so it'simportant to prove this theory through experimental studies.

کلیدواژه ها:

NCAPG gene ، Pediatric Hepatocellular Carcinoma (HCC) ، Prediction analysis ، Missense mutation ، Condensin I complex