Csnk1g3, a member of the casein kinase 1γ subfamily, is involved in multiple biological processes. Casein kinases play roles in phosphorylation, which can regulate various cellular functions, and Csnk1g3 may participate in related signaling pathways [1]. It has been associated with multiple diseases, highlighting its biological importance. Gene knockout models, like those in cultured HeLa cells, can be used to study its function [1].

In triple-negative breast cancer (TNBC), the curcumin derivative N17 targets CSNK1G3 to inhibit p-AKT(S473), leading to cell death, suppression of cell proliferation, blocking of the epithelial-mesenchymal transition process, and induction of apoptosis, indicating CSNK1G3's role as an anti-cancer regulator in TNBC [2]. In a study on the Taiwanese Han people, CSNK1G3 was among the genes showing signatures of positive natural selection, and it was associated with metabolic-related traits, suggesting its role in the population's evolutionary adaptation [3]. In C57BL/6 black mice, the gene expression of CSNK1G3 was significantly low in lesional skin of depigmented mice, indicating its possible involvement in the process of autoimmune-induced depigmentation [4]. In epileptic mice, the circRNA-Csnk1g3/Csnk1g3-85aa/CK1γ3/TNF-α signaling pathway in which Csnk1g3 is involved, impacts necroptosis and inflammation of hippocampal neurons, and Jiawei Chaihu Shugan decoction can regulate this pathway to reduce epileptic events [5]. In geese, CSNK1G3 was identified as a gene potentially regulating feather color [6]. In a study screening for factors modulating translation readthrough, siRNAs targeting CSNK1G3 negatively regulated readthrough [7]. In cancer cell research, siRNAs targeting CSNK1G3 enhanced the cell-killing effect of the Akt inhibitor A-443654, suggesting CSNK1G3 may cooperate with Akt [8]. Also, gene-centric analysis in the Norfolk Island population associated SNPs in CSNK1G3 with migraine susceptibility [9].

In conclusion, Csnk1g3 is involved in multiple biological processes and diseases. Its role in cancer, such as TNBC, the evolutionary adaptation of populations, depigmentation, epilepsy, feather color regulation, translation readthrough, cancer cell growth in relation to Akt, and migraine susceptibility, has been revealed through various research models. These findings contribute to understanding the underlying mechanisms of these biological processes and diseases, providing potential targets for further research and treatment strategies.

References:

1. Goto, Asako, Hanada, Kentaro. 2023. Protocol for casein kinase 1γ3 CSNK1G3 gene knockout and recombinant gene expression in cultured HeLa cells. In STAR protocols, 4, 102251. doi:10.1016/j.xpro.2023.102251. https://pubmed.ncbi.nlm.nih.gov/37119140/

2. Huai, Ziyou, Li, Zijian, Xue, Wei, Wei, Qinjun, Wang, Yuanyuan. 2024. Novel curcumin derivatives N17 exert anti-cancer effects through the CSNK1G3/AKT axis in triple-negative breast cancer. In Biochemical pharmacology, 229, 116472. doi:10.1016/j.bcp.2024.116472. https://pubmed.ncbi.nlm.nih.gov/39127154/

3. Lo, Yun-Hua, Cheng, Hsueh-Chien, Hsiung, Chia-Ni, Shen, Chen-Yang, Ko, Wen-Ya. . Detecting Genetic Ancestry and Adaptation in the Taiwanese Han People. In Molecular biology and evolution, 38, 4149-4165. doi:10.1093/molbev/msaa276. https://pubmed.ncbi.nlm.nih.gov/33170928/

4. Al Robaee, Ahmad A, Alzolibani, Abdullateef A, Rasheed, Zafar. 2020. Autoimmune response against tyrosinase induces depigmentation in C57BL/6 black mice. In Autoimmunity, 53, 459-466. doi:10.1080/08916934.2020.1836489. https://pubmed.ncbi.nlm.nih.gov/33084421/

5. Wang, Qin, Qin, Baijun, Yu, Han, Zhou, Yanying, Diao, Limei. 2025. Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice. In Scientific reports, 15, 4649. doi:10.1038/s41598-025-89275-8. https://pubmed.ncbi.nlm.nih.gov/39920301/

6. Ren, Shuang, Lyu, Guangqi, Irwin, David M, Zhang, Shuyi, Wang, Zhe. 2021. Pooled Sequencing Analysis of Geese (Anser cygnoides) Reveals Genomic Variations Associated With Feather Color. In Frontiers in genetics, 12, 650013. doi:10.3389/fgene.2021.650013. https://pubmed.ncbi.nlm.nih.gov/34220935/

7. Chowdhury, H M, Siddiqui, M A, Kanneganti, S, Chowdhury, M W, Nasim, M Talat. . Aminoglycoside-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that competes with translation termination. In Human molecular genetics, 27, 373-384. doi:10.1093/hmg/ddx409. https://pubmed.ncbi.nlm.nih.gov/29177465/

8. Morgan-Lappe, S, Woods, K W, Li, Q, Fesik, S W, Leverson, J D. . RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors. In Oncogene, 25, 1340-8. doi:. https://pubmed.ncbi.nlm.nih.gov/16247451/

9. Stuart, Shani, Benton, Miles C, Eccles, David A, Lea, Rodney A, Griffiths, Lyn R. 2017. Gene-centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility. In Molecular genetics & genomic medicine, 5, 157-163. doi:10.1002/mgg3.270. https://pubmed.ncbi.nlm.nih.gov/28361102/