ISSN 1866-8836
Клеточная терапия и трансплантация

GC-06. In silico study of mutagenic effect of NCSTN gene in development of bone marrow neoplasms

Bogdan O. Shcheglov                                     

School of Medicine, Far Eastern Federal University, Vladivostok, Russia

Contact: Bogdan O. Shcheglov, phone: +7 (914) 718-98-25, e-mail:            

doi 10.18620/ctt-1866-8836-2022-11-3-1-132


Current studies provide data on the involvement of NCSTN gene encoding nicastrin (the major subunit of γ-secretase), in various neoplastic processes. It has also been shown to play a role in regulation of immune cells. Therefore, the study on the functioning of this gene may provide an opportunity to understand the mechanism of neoplasia in different tissues, and to reduce the risk of malignancies in patients with bone marrow dysfunction.

Materials and methods

At the beginning of this study, each of the gene isoform annotations was compared with mRNAs and ESTs data to select the annotated version. After this analysis, we may state that each annotation has isoforms carrying extra information about the gene, e.g., additional exons which are not mapped in mRNAs and ESTs, or absence of protein-encoding exons. These data were further analyzed for ability of this gene to encode proteins, transcription, expression, and interaction with proteins.


The NCSTN gene is present on the chromosome 21. It includes 17 exons and 16 introns being located on the plus chain, thus indirectly indicating to its protein-encoding function. The gene is unique due to the presence of repeats only in introns, there are no pseudogenes, according to the BLAST database. The gene is annotated correctly, and its structure is true, since the peaks of the transcription track coincide with exons of the annotated isoforms. When examining the gene for protein-coding ability, we may conclude that, for each exon, the signal translational peaks obtained experimentally correspond to the annotated protein-coding regions of the gene. Most peaks of the ribosomal profiling correlate with translated peptides, thus presuming this gene to have a protein-coding function. Analysis of the gene by RNA-seq track data and CAGE peaks was based on the results obtained in A549 cell culture. When analyzing the RNA-seq data, we may suggest that 65.4% of RNA remains in the nucleus and 34.6% is released to the cytoplasm. According to the CAGE data, 72.4% of RNA remains in the nucleus and 27.6% migrates to the cytoplasm. The presented RNA-seq and CAGE data were compatible, i.e., the cytoplasm contains protein-translating RNA. Examination of the gene for mutations in the OMIM Genes database indicates that the gene has a mutation and can cause autosomal dominant inherited disorders manifesting by familial acne, familial purulent hydradenitis with bone marrow dysfunction. The encoded proteins cleave integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, thus, probably, being a stabilizing cofactor required for assembly of the gamma-secretase complex. Similarly, according to the Gene Interactions track, this gene controls some protein-protein interactions that would be disrupted by gene mutations in absence of a final functional protein product.


Upon the data analysis, we may conclude that the point mutations of the gene, including those found in tumor samples, coincide with the coding sequences of exons. Moreover, the COSMIC Regions database contains information on the point mutations of this gene found in tumors, e.g., malignant melanomas, adenomas, carcinomas, sarcomas, gliomas, and in lymphoid neoplasms. These disorders arise not only due to point mutations in the coding gene sequences, as displayed in the COSMIC Regions, ClinVar Short Variants, and HGMD Variants databases, but also occur due to deletions and duplications affecting the entire length of this gene, as displayed in the ClinVar Long Variants and Development Delay databases.


Bone marrow, transcriptomics, NCSTN gene.

Volume 11, Number 3

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doi 10.18620/ctt-1866-8836-2022-11-3-1-132

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