BAK1, also known as BCL2 homologous antagonist/killer 1, is a key pro-apoptotic effector protein encoded by the human BAK1 gene. It is a critical regulator in the apoptotic machinery, with its protein structure and function closely related to apoptosis. BAK1 is involved in mitochondrial outer membrane permeabilization (MOMP), a central step in apoptosis execution, and its function is intertwined with other members of the BCL2 family, such as BAX [3,5].

Studies have revealed several associations related to BAK1. The rs210138 polymorphism in BAK1 is associated with an increased risk of testicular germ cell tumors (TGCT), where the G allele compared to A increases the risk [1]. In preeclampsia, hsa_circ_0002348 regulates trophoblast proliferation and apoptosis through the miR-126-3p/BAK1 axis. Hsa_circ_0002348 acts as a sponge for miR-126-3p, upregulating BAK1 expression, which in turn affects trophoblast function [2]. Regarding abdominal aortic aneurysms (AAA), specific BAK1 single-nucleotide polymorphisms (SNPs) were found in aneurysmic and healthy aortic tissues but not in matching blood samples, suggesting a role of gene selection in AAA ontogeny [4]. A 4-bp deletion polymorphism in an enhancer adjacent to BAK1 (rs3831846) reduces enhancer activity and confers risk of intracranial germ cell tumors (IGCTs), and it is in strong linkage disequilibrium with a TGCTs susceptibility variant [6].

In conclusion, BAK1 plays a crucial role in apoptosis, and its genetic variations are associated with various diseases including testicular and intracranial germ cell tumors, preeclampsia, and abdominal aortic aneurysms. These disease-related associations highlight the importance of understanding BAK1's function and genetic polymorphisms, which may provide insights into disease mechanisms and potential therapeutic targets.

References:

1. Qin, Jiaxuan, Yang, Yufeng, Zhuang, Xuan, Xing, Jinchun. 2020. Association Between BAK1 Gene rs210138 Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-Analysis. In Frontiers in endocrinology, 11, 2. doi:10.3389/fendo.2020.00002. https://pubmed.ncbi.nlm.nih.gov/32038496/

2. Zhou, Jizi, Zhao, Ying, An, Ping, Li, Xiaotian, Xiong, Yu. 2023. Hsa_circ_0002348 regulates trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in preeclampsia. In Journal of translational medicine, 21, 509. doi:10.1186/s12967-023-04240-1. https://pubmed.ncbi.nlm.nih.gov/37507742/

3. Cosentino, Katia, Hertlein, Vanessa, Jenner, Andreas, Ries, Jonas, Garcia-Saez, Ana J. 2022. The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation. In Molecular cell, 82, 933-949.e9. doi:10.1016/j.molcel.2022.01.008. https://pubmed.ncbi.nlm.nih.gov/35120587/

4. Gottlieb, Bruce, Chalifour, Lorraine E, Mitmaker, Benjamin, Bkaily, Ghassan, Schweitzer, Morris. . BAK1 gene variation and abdominal aortic aneurysms. In Human mutation, 30, 1043-7. doi:10.1002/humu.21046. https://pubmed.ncbi.nlm.nih.gov/19514060/

5. Dadsena, Shashank, Cuevas Arenas, Rodrigo, Vieira, Gonçalo, Melo, Manuel N, García-Sáez, Ana J. 2024. Lipid unsaturation promotes BAX and BAK pore activity during apoptosis. In Nature communications, 15, 4700. doi:10.1038/s41467-024-49067-6. https://pubmed.ncbi.nlm.nih.gov/38830851/

6. Sonehara, Kyuto, Kimura, Yui, Nakano, Yoshiko, Okada, Yukinori, Terashima, Keita. 2022. A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors. In Nature communications, 13, 4478. doi:10.1038/s41467-022-32005-9. https://pubmed.ncbi.nlm.nih.gov/35918310/