Proteins family members consist of four paralogues, namely KDM4A- KDM4D, and two pseudogenes, KDM4E and KDM4F. When KDM4A and KDM4B are the widely-studied members with the KDM4 subfamily, the roles of KDM4E in cancers have hardly ever been reported (Wang et al., 2022a). Genomic alterations and overexpression with the KDM4 loved ones are reported in distinct breast cancer subtypes. Many KDM4 inhibitors have already been employed as anticancer drugs for breast cancers in vitro (Ye et al., 2015; Varghese et al., 2021). Nevertheless, none of these drugs have undergone clinical trials yet (Varghese et al., 2021). The bioinformatics analysis demonstrated that the intronless KDM4E and KDM4F are expressed similarly to KDM4D. Due to their architecture and lack of expression, KDM4E and KDM4F are known as pseudogenes (Berry and Janknecht, 2013). Developing evidence that the pseudogenes have a wide variety of biological roles and that their dysregulation is often linked to human problems like cancer signifies their prospective as therapeutic targets (Prensner and Chinnaiyan, 2011; Wahlestedt,Frontiers in Molecular Biosciencesfrontiersin.orgMohd Yunos et al.PFKM Protein Purity & Documentation 10.3389/fmolb.2022.2013; Sisu, 2021). Various genomic alterations of pseudogenes in CRC have already been identified. As an example, pseudogenes DUXAP8, MST O 2P and MYLKP1 involved in supporting CRC progression and boost cancer threat (Lynn et al., 2018; He et al., 2020; Guo and Zhang, 2022). Hence, it can be worth to explore the molecular characteristic and functional relevance on the identified recurrent KDM4E R100H mutation to unravel their potential as therapeutic target in CRC. In this present study, we’ve identified a recurrent, nonsynonymous MUC16 L12755S mutation which was predicted to become deleterious by SIFT and PolyPhen-2 tools. Positioned inside the tandem repeat domain, this distinct mutation has not been previously reported in CRC and is worth exploring its functional relevance in future research.The MUC16 gene encodes to get a very glycosylated protein that consists of two main domains: a tandem repeat domain (interspersed with SEA domain) containing the CA-125 epitope and also a transmembrane domain (Hattrup and Gendler, 2008; Felder et al., 2014). CA-125 is an FDA-approved serum biomarker used in monitoring cancer progression and remedy response, particularly in ovarian cancer (Bottoni and Scatena, 2015; Li et al., 2018; Charkhchi et al., 2020). MUC16 will be the most regularly mutated gene in endometrial cancer (Hu and Sun, 2018), and its oncogenic properties have already been investigated in numerous other cancers including glioblastoma (Yang C.AGRP Protein Purity & Documentation et al.PMID:23453497 , 2019), gastric cancer (Huang et al., 2021) and colorectal cancer (Bj kman et al., 2019). Meanwhile, knocking down MUC16 in CRC cells impaired their development and metastatic capability as a consequence of the deregulation of JAK2-STAT3 signalling pathway(Liu et al., 2022). Additionally, a considerable correlation among the MUC16 mutation with tumour mutational burden and microsatellite status was shown in sufferers with gastric cancer (Zhang et al., 2022), colorectal cancer (Wang et al., 2020), and melanoma (Zhang et al., 2020; Wang et al., 2022b) which signifies the employed of immune checkpoint inhibitor (ICI) in the remedy regimen. To our expertise, our study will be the initially to report novel POTED E172Q mutation in CRC, which had been discovered in two of our patients. POTE family gene has at least ten paralogs, which encode for cancer testis antigens (CTAs) that are expressed within the germ cells of t.