The RNF213 gene encodes a cytosolic protein consisting of a RING finger domain and two AAA+ ATPase domains. The protein possesses E3 ubiquitin ligase activity and ATPase activity and it specifically targets FLNA and NFATC2 downstream of RSPO3 for ubiquitination and subsequent degradation. This leads to the inhibition of the non-canonical Wnt signaling pathway involved in vascular development. The protein thus plays a key role in angiogenesis, particularly in sprouting angiogenesis.
Genome wide association studies have helped identify a link between RNF213 mutations and susceptibility to Moyamoya Disease 2, a disorder characterized by intracranial carotid artery occlusion, basal ganglia telangiectases and inflammatory arteriopathy. Animal studies have helped reinforce the role of the protein in vascular growth; knockdown of the RNF213 ortholog in zebrafish has been found to result in abnormal vascular development, notably causing deficient sprouting vessels in the head.