Pcdhb6, a member of the protocadherin beta gene cluster, is likely involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules, as genes in this functional category were highlighted in gene ontology analysis related to ischemic stroke [2]. It may also be associated with pathways related to cell adhesion based on studies in a mouse model of partial monosomy 21 [3]. Additionally, it has potential links to neurodevelopment as it was identified among genes related to this process in goats [4], and may be associated with neurocognitive outcomes considering its inclusion in a study on the effect of maternal folate depletion on gene methylation in the murine brain [5]. It was also proposed as a novel candidate gene affecting milk protein composition traits in Chinese Holstein cows [6].

In a study on hepatocellular carcinoma (HCC), subclass HCCW4, which was associated with a poor prognosis, had the highest PCDHB6 expression. This subclass also had a relatively high abundance of certain immune cells, high Edmondson-Steiner grades, and low enrichment of some other immune cell types, suggesting a potential role of Pcdhb6 in the tumor microenvironment and prognosis of HCC [1]. In the study on ischemic stroke, the methylation level of Pcdhb6 was among those investigated, and the methylation of 7 related genes was proposed as a potential diagnostic biomarker for ischemic stroke [2].

In conclusion, Pcdhb6 appears to be involved in cell adhesion, potentially neurodevelopment, and has implications in diseases such as HCC and ischemic stroke. Studies, including those on mouse models and in different species, have provided insights into its role in these biological processes and disease conditions, highlighting its importance in understanding disease mechanisms.

References:

1. Chang, Ya-Sian, Chou, Yu-Pao, Chung, Chin-Chun, Jeng, Long-Bin, Chang, Jan-Gowth. 2022. Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes. In Cancers, 14, . doi:10.3390/cancers14194580. https://pubmed.ncbi.nlm.nih.gov/36230503/

2. Sun, Hongwei, Xu, Jia, Hu, Bifeng, Tang, Ying, Zhao, Jingbo. 2022. Association of DNA Methylation Patterns in 7 Novel Genes With Ischemic Stroke in the Northern Chinese Population. In Frontiers in genetics, 13, 844141. doi:10.3389/fgene.2022.844141. https://pubmed.ncbi.nlm.nih.gov/35480311/

3. Arbogast, Thomas, Raveau, Matthieu, Chevalier, Claire, Duchon, Arnaud, Herault, Yann. 2015. Deletion of the App-Runx1 region in mice models human partial monosomy 21. In Disease models & mechanisms, 8, 623-34. doi:10.1242/dmm.017814. https://pubmed.ncbi.nlm.nih.gov/26035870/

4. Luo, Jing, Min, Qi, Sun, Xueliang, Han, Yanguo, Li, Li. 2024. Comparative Whole-Genome Analysis of Production Traits and Genetic Structure in Baiyu and Chuanzhong Black Goats. In Animals : an open access journal from MDPI, 14, . doi:10.3390/ani14243616. https://pubmed.ncbi.nlm.nih.gov/39765520/

5. Kok, Dieuwertje E, Saunders, Rachael, Nelson, Andrew, Mathers, John C, McKay, Jill A. . Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health. In Mutagenesis, 39, 196-204. doi:10.1093/mutage/geae007. https://pubmed.ncbi.nlm.nih.gov/38417824/

6. Zhou, Chenghao, Li, Cong, Cai, Wentao, Zhang, Qin, Zhang, Shengli. 2019. Genome-Wide Association Study for Milk Protein Composition Traits in a Chinese Holstein Population Using a Single-Step Approach. In Frontiers in genetics, 10, 72. doi:10.3389/fgene.2019.00072. https://pubmed.ncbi.nlm.nih.gov/30838020/