IN-SILICO CHARACTERIZATION OF NON-SYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS IN HUMAN MDM2: IMPLICATIONS FOR CANCER SUSCEPTIBILITY

Main Article Content

Awais Khan
Azhar Hussain Shah
Syed Basit Ali Shah
Aatka Jamil
Khuzin Dinislam
Attiq Ullah

Keywords

MDM2, Oncogene, Cancer biology, Therapeutic targets, Nucleotide polymorphisms, Non-Synonymous Single Nucleotide Polymorphisms

Abstract

The oncogene MDM2 (Murine Double Minute 2) was first found in DNA and bound to the paired acentric chromosome. 0SNPs (single nucleotide polymorphisms) are important for determining the genetic basis of several complicated human disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) are mutation in only a one nucleotide in sequences of any gene that has changed the specific synthesized protein in its function, structure and morphogenesis. Finding the affected SNPs in the genetic make-up of diseases remains a difficult task. The present Insilico study explored and identified the genetic variation that affects and modifies the expression of MDM2 genes. SIFT found that 36 SNPs in the MDM2 gene are harmful while polyphen2 analyzed 12 SNPs in MDM2 gene. An aggregate result was obtained by examining six tools with diverse views, and seven nsSNPs were shown to be the most likely to have a detrimental impact. I-Mutant and Project HOPE approaches were utilized to predict the mutant proteins' severe structural and functional instability, while the InterPro was utilised the predict SNP in crucial functional domains. Only 9 SNPs rs764034976, rs753663917, rs761546875, rs755429424, rs764918809, rs763077439, rs765555199, rs1475420873 and rs550783815 were discovered that influence the structure, function, and stability of the MDM2 protein synthesized by MDM2 gene. To our knowledge, there has never been any research on the SNPs of the MDM2 gene. This is the first study on the MDM2 gene using computation methods.

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