Efhc1, also known as myoclonin1 or Rib72-1, is a gene of significance. The protein it encodes is associated with microtubules and has been implicated in regulating cell division [3]. It is also involved in motile cilia function and may play a role in neuronal sensory input and output by modulating dopamine signaling at the cilium and synapse [5]. Mutations in Efhc1 have been linked to juvenile myoclonic epilepsy (JME), a common form of genetic generalized epilepsies [2,3,4].

Using Efhc1 homozygous knock-out (Efhc1-/-) mice, research has shown that myoclonin1, the protein encoded by Efhc1, is not expressed in neurons or mitotic apparatuses in the brain but is expressed in cells with motile cilia such as choroid plexus and ependymal cells. The complete elimination of myoclonin1 in Efhc1-/-mice did not critically affect cell division and migration of neurons in the cerebral cortex, suggesting that EFHC1 mutation-dependent JME may be a motile ciliopathy [1]. Functional studies on mutations identified in JME patients suggest that these EFHC1 mutations result in microtubule-related abnormalities during cell division [4].

In conclusion, Efhc1 is important for functions related to cell division, motile cilia, and dopamine signaling. Model-based research, especially with Efhc1-/-mice, has been crucial in revealing its role in JME, indicating that disruptions in its normal functions may lead to this form of epilepsy.

References:

1. Suzuki, Toshimitsu, Inoue, Ikuyo, Yamakawa, Kazuhiro. 2020. Epilepsy protein Efhc1/myoclonin1 is expressed in cells with motile cilia but not in neurons or mitotic apparatuses in brain. In Scientific reports, 10, 22076. doi:10.1038/s41598-020-79202-4. https://pubmed.ncbi.nlm.nih.gov/33328576/

2. de Nijs, Laurence, Wolkoff, Nathalie, Grisar, Thierry, Lakaye, Bernard. . Juvenile myoclonic epilepsy as a possible neurodevelopmental disease: role of EFHC1 or Myoclonin1. In Epilepsy & behavior : E&B, 28 Suppl 1, S58-60. doi:10.1016/j.yebeh.2012.06.034. https://pubmed.ncbi.nlm.nih.gov/23756481/

3. de Nijs, Laurence, Léon, Christine, Nguyen, Laurent, Grisar, Thierry, Lakaye, Bernard. 2009. EFHC1 interacts with microtubules to regulate cell division and cortical development. In Nature neuroscience, 12, 1266-74. doi:10.1038/nn.2390. https://pubmed.ncbi.nlm.nih.gov/19734894/

4. Raju, Praveen K, Satishchandra, Parthasarathy, Nayak, Sourav, Sinha, Sanjib, Anand, Anuranjan. 2017. Microtubule-associated defects caused by EFHC1 mutations in juvenile myoclonic epilepsy. In Human mutation, 38, 816-826. doi:10.1002/humu.23221. https://pubmed.ncbi.nlm.nih.gov/28370826/

5. Loucks, Catrina M, Park, Kwangjin, Walker, Denise S, Rankin, Catharine H, Leroux, Michel R. 2019. EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling. In eLife, 8, . doi:10.7554/eLife.37271. https://pubmed.ncbi.nlm.nih.gov/30810526/