Computational and Pathway Analysis of nsSNPs of MED23 Gene Involved in Human Congenital Diseases

Author(s): Muhammad Naveed*, Komal Imran, Ayesha Mushtaq.

Journal Name: Current Biotechnology

Volume 7 , Issue 2 , 2018

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Abstract:

Background: Mediator complex subunit 23 (MED23) is a transcriptional mediator of RNA polymerase II and essential for heat-shock-specific gene expression in humans. Mutations in MED23 gene cause neural diseases. Therefore, prior to a population study, it is important to uncover different deleterious single nucleotide polymorphisms (SNPs) structural and functional effects within MED23 encoded protein.

Methods: The present study identified functional nsSNPs in MED23 and its effect on protein signaling cascade. The SNPs were retrieved from a dbSNP database and potentially deleteriousness SNPs were identified through in-silico screening with SIFT, the Polyphen server and PANTHER. Furthermore, protein structural prediction & validation of wild-type and mutated proteins were achieved through ITASSER and ProsA. At the end, protein-protein interactions and pathway analysis were conducted through STRING and literature review to uncover the effects of deleterious nsSNP to the MED23 protein biological function in the body.

Results: The current approach predicted, the most pathogenic nsSNP is rs104893948 G235R exhibit position- specific evolutionary preservation induces the major damage to protein stability by disturbing its natural function and amino acid interactions. Destabilized MED23 protein provoked transcriptional dysregulation of enhancer based transcriptional factors presenting neurologic disorders and impaired brain development.

Conclusion: In the future, mapping of G235R nsSNPs in MED23 gene would provide valuable information about population study and can apply as diagnostic markers for neural deformities and vascular diseases. Tumor suppressor in-vitro role of MED23 is needed to be explored among individuals carrying these polymorphisms to enhance our knowledge about complex mechanisms of this protein in several congenital human diseases.

Keywords: nsSNP, MED23, neural and congenital human diseases, RhoA, Ras, SMCs.

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Article Details

VOLUME: 7
ISSUE: 2
Year: 2018
Page: [132 - 147]
Pages: 16
DOI: 10.2174/2211550107666180119154308
Price: $58

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