Rnf213, also known as Mysterin, is a significant gene with a 591-kDa cytosolic protein product that contains a Walker motif, a RING finger domain, and an RZ finger. It has ATPase and ubiquitin ligase activities and is involved in multiple biological processes such as angiogenesis, lipid metabolism, and immune response [2,4,5]. Rnf213 is strongly associated with moyamoya disease, an uncommon cerebrovascular disorder, and may also be related to other systemic vascular diseases like intracranial artery dissection [1,2,3,6].

In Rnf213-deficient mice and zebrafish, deletion of Rnf213 exacerbated pathological angiogenesis in the cortex and retina [1]. In human brain microvascular endothelial cells, knockdown of Rnf213 led to increased cell proliferation, migration, and tube formation, activating the Hippo pathway effector Yes-associated protein (YAP)/tafazzin (TAZ) and promoting overexpression of the downstream effector VEGFR2 [1].

In conclusion, Rnf213 plays essential roles in angiogenesis and immune-related processes. Research using Rnf213-deficient mouse models has significantly contributed to understanding its role in moyamoya disease, highlighting its importance in the pathogenesis of this cerebrovascular disorder and potentially other related vascular diseases [1].

References:

1. Ye, Fei, Niu, Xingyang, Liang, Feng, Qi, Tiewei, Sheng, Wenli. . RNF213 loss-of-function promotes pathological angiogenesis in moyamoya disease via the Hippo pathway. In Brain : a journal of neurology, 146, 4674-4689. doi:10.1093/brain/awad225. https://pubmed.ncbi.nlm.nih.gov/37399508/

2. Fang, Jianxun, Yang, Xinzhuang, Ni, Jun. 2024. RNF213 in moyamoya disease: Genotype-phenotype association and the underlying mechanism. In Chinese medical journal, 137, 2552-2560. doi:10.1097/CM9.0000000000002985. https://pubmed.ncbi.nlm.nih.gov/38243713/

3. Zedde, Marialuisa, Grisendi, Ilaria, Assenza, Federica, Valzania, Franco, Pascarella, Rosario. 2024. RNF213 Polymorphisms in Intracranial Artery Dissection. In Genes, 15, . doi:10.3390/genes15060725. https://pubmed.ncbi.nlm.nih.gov/38927660/

4. Liu, Wanyang, Morito, Daisuke, Takashima, Seiji, Hashimoto, Nobuo, Koizumi, Akio. 2011. Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. In PloS one, 6, e22542. doi:10.1371/journal.pone.0022542. https://pubmed.ncbi.nlm.nih.gov/21799892/

5. Pollaci, Giuliana, Gorla, Gemma, Potenza, Antonella, Bersano, Anna, Gatti, Laura. 2022. Novel Multifaceted Roles for RNF213 Protein. In International journal of molecular sciences, 23, . doi:10.3390/ijms23094492. https://pubmed.ncbi.nlm.nih.gov/35562882/

6. Murai, Yasuo, Matano, Fumihiro, Kubota, Asami, Nakae, Ryuta, Tamaki, Tomonori. . RNF213-Related Vasculopathy: Various Systemic Vascular Diseases Involving RNF213 Gene Mutations: Review. In Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 91, 140-145. doi:10.1272/jnms.JNMS.2024_91-215. https://pubmed.ncbi.nlm.nih.gov/38777780/