64
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Prediction of deleterious non-synonymous SNPs of human MDC1 gene: an in silico approach

, ORCID Icon & ORCID Icon
Pages 101-112 | Received 22 Jun 2023, Accepted 24 Feb 2024, Published online: 17 Apr 2024
 

Abstract

MDC1 (Mediator of DNA damage Checkpoint protein 1) functions to facilitate the localization of numerous DNA damage response (DDR) components to DNA double-strand break sites. MDC1 is an integral component in preserving genomic stability and appropriate DDR regulation. There haven’t been systematic investigations of MDC1 mutations that induce cancer and genomic instability. Variations in nsSNPs have the potential to modify the protein chemistry and their function. Describing functional SNPs in disease-associated genes presents a significant conundrum for investigators, it is possible to assess potential functional SNPs before conducting larger population examinations. Multiple sequences and structure-based bioinformatics strategies were implemented in the current in-silico investigation to discern potential nsSNPs of the MDC1 genes. The nsSNPs were identified with SIFT, SNAP2, Align GVGD, PolyPhen-2, and PANTHER, and their stability was determined with MUpro. The conservation, solvent accessibility, and structural effects of the mutations were identified with ConSurf, NetSurfP-2.0, and SAAFEC-SEQ respectively. Cancer-related analysis of the nsSNPs was conducted using cBioPortal and TCGA web servers. The present study appraised five nsSNPs (P1426T, P69S, P194R, P203L, and H131Y) as probably mutilating due to their existence in highly conserved regions and propensity to deplete protein stability. The nsSNPs P194R, P203L, and H131Y were concluded as deleterious and possibly damaging from the 5 prediction tools. The functional nsSNP P194R mutation is associated with skin cutaneous melanoma while no significant records were found for other nsSNPs. The present study concludes that the highly deleterious P194R mutations can potentially induce genomic instability and contribute to various cancers’ pathogenesis. Developing drugs targeting these mutations can undoubtedly be advantageous in large population-based studies, particularly in the development of precision medicine.

Authors' contribution

VT: Performed the experiments and analyzed the data; SD: Wrote the manuscript and edited the paper; SS: Conceived and designed the experiment.

Disclosure statement

No potential conflict of interest was reported by the authors.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.