UNC13B, also known as unc-13 homolog B, encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2). It is highly expressed in the brain, predominantly in the cerebral cortex, and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability [1]. It belongs to the Uncoordinated-13 (UNC13) protein family which is crucial for synaptic vesicle priming and exocytosis, and has implications in multiple human diseases [3].

In functional studies, UNC13B variants were identified in individuals with partial epilepsy and/or febrile seizures. All patients with these variants showed a favorable outcome without intellectual or developmental abnormalities. Computational modelling suggested the variants lead to functional impairment. In Drosophila, Unc13b knockdown increased seizure rate and duration, and electrophysiological recordings showed increased excitability in Unc13b-deficient flies, indicating its potential association with epilepsy [1]. In K-562 cells, UNC13B downregulation significantly inhibited growth, promoted apoptosis, and decreased colony formation, suggesting it may be a potential therapeutic target for arsenic trioxide-resistant chronic myeloid leukemia [2]. In Wilms' tumor 17.94 cell line, UNC13B knockdown increased apoptosis levels upon doxorubicin treatment, indicating it regulates the sensitivity of these cells to doxorubicin by modulating lysosome formation [4].

In conclusion, UNC13B is essential for synaptic vesicle-related functions in the brain. Studies using knockdown models in Drosophila and cell-based models like K-562 and Wilms' tumor cells have revealed its potential roles in epilepsy, arsenic trioxide-resistant chronic myeloid leukemia, and modulating drug sensitivity in Wilms' tumor. These findings contribute to understanding the biological functions of UNC13B and its implications in these disease areas.

References:

1. Wang, Jie, Qiao, Jing-Da, Liu, Xiao-Rong, Gu, Wei-Yue, Liao, Wei-Ping. . UNC13B variants associated with partial epilepsy with favourable outcome. In Brain : a journal of neurology, 144, 3050-3060. doi:10.1093/brain/awab164. https://pubmed.ncbi.nlm.nih.gov/33876820/

2. Wang, Xiao-Bo, Yuan, Li-Hua, Yan, Le-Ping, Lu, Bo, Xu, Xiaojun. 2022. UNC13B Promote Arsenic Trioxide Resistance in Chronic Lymphoid Leukemia Through Mitochondria Quality Control. In Frontiers in oncology, 12, 920999. doi:10.3389/fonc.2022.920999. https://pubmed.ncbi.nlm.nih.gov/35707364/

3. Ansari, Ubaid, Chen, Vincent, Sedighi, Romteen, Razick, Daniel, Lui, Forshing. 2023. Role of the UNC13 family in human diseases: A literature review. In AIMS neuroscience, 10, 388-400. doi:10.3934/Neuroscience.2023029. https://pubmed.ncbi.nlm.nih.gov/38188011/

4. Chen, Xi, Bao, Yingying, Sun, Ge, Wang, Xiaobo, Zhu, Jiajun. 2024. UNC13B regulates the sensitivity of Wilms' tumor cells to doxorubicin by modulating lysosomes. In Oncology letters, 28, 446. doi:10.3892/ol.2024.14579. https://pubmed.ncbi.nlm.nih.gov/39091580/