CACNA1G encodes the α1G subunit of the thalamus-enriched T-type calcium channel, also known as Ca(V)3.1, a low-threshold voltage-gated T-type calcium channel. T-type calcium channels are involved in various cellular processes, such as regulating membrane potential, controlling the firing patterns of neurons, and participating in calcium-dependent signaling pathways. Their functions are crucial for normal neural development, synaptic transmission, and the overall physiological function of the nervous system [1,2,3].

In mouse models of epilepsy, genetic modification of Cacna1g expression has shown significant impacts. In the Scn1a+/- Dravet syndrome mouse model, decreased Cacna1g expression led to partial amelioration of disease phenotypes, including improved survival and reduced spontaneous seizure frequency [4]. In the Scn2a(Q54) transgenic epilepsy mouse model, elevated Cacna1g expression increased spontaneous seizure frequency, while decreased expression decreased seizure frequency [5]. These findings suggest that Cacna1g is a genetic modifier of epilepsy in these mouse models, indicating its potential as a molecular target for therapeutic intervention in epilepsy patients.

In conclusion, Cacna1g plays a vital role in regulating the function of T-type calcium channels, which is essential for normal neural function. Mouse models, especially those with gene knockout or modification of Cacna1g expression, have provided valuable insights into its role in epilepsy. Understanding Cacna1g's function may offer new strategies for treating epilepsy and potentially other neurological disorders associated with its genetic variants [1,2,3,4,5].

References:

1. Kim, Ji-Il, Miura, Yuki, Li, Min-Yin, Huguenard, John R, Pașca, Sergiu P. 2024. Human assembloids reveal the consequences of CACNA1G gene variants in the thalamocortical pathway. In Neuron, 112, 4048-4059.e7. doi:10.1016/j.neuron.2024.09.020. https://pubmed.ncbi.nlm.nih.gov/39419023/

2. De Riggi, Martina, De Giorgi, Agnese, Pollini, Luca, Galosi, Serena, Bologna, Matteo. 2024. CACNA1G Causes Dominantly Inherited Myoclonus-Ataxia with Intellectual Disability: A Case Report. In Cerebellum (London, England), 23, 2679-2683. doi:10.1007/s12311-024-01734-6. https://pubmed.ncbi.nlm.nih.gov/39287920/

3. Kessi, Miriam, Chen, Baiyu, Peng, Jing, Yang, Lifen, Yin, Fei. 2021. Calcium channelopathies and intellectual disability: a systematic review. In Orphanet journal of rare diseases, 16, 219. doi:10.1186/s13023-021-01850-0. https://pubmed.ncbi.nlm.nih.gov/33985586/

4. Calhoun, Jeffrey D, Hawkins, Nicole A, Zachwieja, Nicole J, Kearney, Jennifer A. 2017. Cacna1g is a genetic modifier of epilepsy in a mouse model of Dravet syndrome. In Epilepsia, 58, e111-e115. doi:10.1111/epi.13811. https://pubmed.ncbi.nlm.nih.gov/28556246/

5. Calhoun, Jeffrey D, Hawkins, Nicole A, Zachwieja, Nicole J, Kearney, Jennifer A. 2016. Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a. In Epilepsia, 57, e103-7. doi:10.1111/epi.13390. https://pubmed.ncbi.nlm.nih.gov/27112236/