Abstract:
A single-nucleotide polymorphism (SNP) is a naturally occurring variation in genomic DNA.
Untranslated regions (UTRs) are involved in the regulatory pathways of cells that influence transcriptional and
translational mechanisms. PRKCH belongs to the Protein Kinase C (PKC) family, which regulates crucial cellular
processes. Limited studies have explored the regulatory and functional impact of UTR variants of PRKCH through
in silico and genotyping analysis.,which was the focus of the current study. Pathogenic potential of UTR variants
was critically analyzed. Meanwhile, among the 3′UTR variants, the only variant rs14095 (A/G) was ranked as 1f
by RegulomeDB and showed a allelic frequency in African populations. This variant also interacted with miRNA
“hsa-miR-6074”, which has been reported to regulate “TRP channels” through the KEGG pathway. The 5′UTR
variants, including rs114416617 G/A, rs145795985 G/A, rs1951964 C/G, and rs45582331 C/G showed allelic
frequency in different populations along with their expression in various organs. Motifs were detected in these 4
variants of 5′UTR region. These variants exhibited a strong chromatin profile. hsa-miR-6074 was reported to
regulate p53 signaling, melanoma, FoxO signaling, glioma, MAPK, IL-17, PD-L1, HIF1A, TRAF6, PTEN, carbon
metabolism, autophagy, and cellular senescence related pathways. According to genotyping analysis, the
mutated genotype (GG) of the 3′ UTR variant rs14095 was significantly associated with Hepatocellular Carcinoma
(HCC) risk. In comparison, for the 5′ UTR variant, rs44582331, no significant association was observed
between the mutated genotype (TT) and HCC. Furthermore, functional assays need to be carried out to experimentally
validate the role of these UTR variants in cancer pathogenesis.
