CACNA1C encodes the pore-forming subunit of the CaV1.2 L-type Ca2+ channel, a crucial part of membrane physiology in tissues like the heart, brain, and immune system [1]. This channel is involved in multiple cellular functions, and thus, the gene has significant biological importance. Genetic models can be valuable for studying its function and the impact of its mutations.

Mutations in CACNA1C are associated with a wide range of disorders. Timothy syndrome, a severe multisystem disorder characterized by neurodevelopmental deficits, long-QT syndrome, cardiac arrhythmias, craniofacial abnormalities, and immune deficits, was the first disorder linked to CACNA1C mutations [1]. The gene's variants have also been associated with more isolated neurological manifestations such as developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy [2]. Additionally, genetic variation in CACNA1C increases the risk for psychiatric disorders like schizophrenia and bipolar disorder [3,4,5]. In ovarian cancer, CACNA1C has lower expression in tumor tissues, and it can be an independent risk factor for overall survival, also being related to immunity [6].

In conclusion, CACNA1C is essential for membrane physiology in multiple tissues. Studies on its mutations, often through genetic models, have revealed its role in various disease conditions including multisystem disorders, neurological manifestations, psychiatric disorders, and ovarian cancer. These findings contribute to understanding the biological functions of CACNA1C and provide insights into potential disease mechanisms.

References:

1. Herold, Kevin G, Hussey, John W, Dick, Ivy E. . CACNA1C-Related Channelopathies. In Handbook of experimental pharmacology, 279, 159-181. doi:10.1007/164_2022_624. https://pubmed.ncbi.nlm.nih.gov/36598608/

2. Rodan, Lance H, Spillmann, Rebecca C, Kurata, Harley T, Au, Ping Yee Billie, Shashi, Vandana. 2021. Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations. In Genetics in medicine : official journal of the American College of Medical Genetics, 23, 1922-1932. doi:10.1038/s41436-021-01232-8. https://pubmed.ncbi.nlm.nih.gov/34163037/

3. Moon, Anna L, Haan, Niels, Wilkinson, Lawrence S, Thomas, Kerrie L, Hall, Jeremy. . CACNA1C: Association With Psychiatric Disorders, Behavior, and Neurogenesis. In Schizophrenia bulletin, 44, 958-965. doi:10.1093/schbul/sby096. https://pubmed.ncbi.nlm.nih.gov/29982775/

4. Zhu, Dongjian, Yin, Jingwen, Liang, Chunmei, Wang, Yajun, Ma, Guoda. 2019. CACNA1C (rs1006737) may be a susceptibility gene for schizophrenia: An updated meta-analysis. In Brain and behavior, 9, e01292. doi:10.1002/brb3.1292. https://pubmed.ncbi.nlm.nih.gov/31033230/

5. Harrison, Paul J, Husain, Syed M, Lee, Hami, Haerty, Wilfried, Tunbridge, Elizabeth M. 2022. CACNA1C (CaV1.2) and other L-type calcium channels in the pathophysiology and treatment of psychiatric disorders: Advances from functional genomics and pharmacoepidemiology. In Neuropharmacology, 220, 109262. doi:10.1016/j.neuropharm.2022.109262. https://pubmed.ncbi.nlm.nih.gov/36154842/

6. Chang, Xiaohan, Dong, Yunxia. 2021. CACNA1C is a prognostic predictor for patients with ovarian cancer. In Journal of ovarian research, 14, 88. doi:10.1186/s13048-021-00830-z. https://pubmed.ncbi.nlm.nih.gov/34210324/