Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India

•p53 pathway harborsthe maximum percentage of clinically deleterious variants.•rs138941861 in STEAP3 gene was the most deleterious exonic unique-case variant.•STEAP3_Arg290His (rs138941861) variant affecting ESP alter functionality of protein.•STEAP3 is probably associated with EBV-mediatedNPC pathogenesis.•12 non-coding variants showed significant change in splicing site as well as TFBSs. Nasopharyngeal Carcinoma (NPC) found to be dependent on geographical and racial variation and is more prevalent in Northeast (NE) India. WES-based study was conducted in three states (tribes); Nagaland (Naga), Mizoram (Mizo) and Manipur (Manipuri), which provided an overview of germline variants involved inthemajor signaling pathways. Validation and recurrence assessment of WES data confirmed the risk effect of STEAP3_rs138941861 and JAG1_rs2273059, and the protective role of PARP4_rs17080653 and TGFBR1_rs11568778 variants, where STEAP3_rs138941861conferring Arg290His substitution was the only exonic non-synonymous variant and to be located in proximity to the linking region between the transmembrane and oxidoreductasedomainsof STEAP3 protein, andaffectedits structural and functional dynamics by altering the Electrostatic Potential around this connecting region. Moreover, these significantly associated variants having deleterious effect were observed to have interactions in p53 signaling pathway which emphasizes the importance of this pathway in the causation of NPC.