RNF213 Gene: Moyamoya Disease, Cancer, and the RING Finger E3 Ligase
Explore the RNF213 gene, its role in Moyamoya disease and cancer, protein function, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | RNF213 |
|---|---|
| Full Name | Ring Finger Protein 213 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 57625 ncbi.nlm.nih.gov/gene/57625 |
| Ensembl ID | ENSG00000173821 |
| UniProt ID | Q63HN8 |
| OMIM ID | 613768 |
| HGNC ID | 18739 |
| Aliases | AL022722, C17orf27, KIAA1618, MYMY2, RNF213A |
Description
RNF213 encodes a large protein (5200 amino acids) that functions as an E3 ubiquitin ligase and ATPase. It is involved in angiogenesis, vascular development, and inflammatory responses. Mutations in RNF213 are strongly associated with Moyamoya disease, a cerebrovascular disorder characterized by progressive stenosis of intracranial arteries. Additionally, RNF213 has been implicated in cancer, particularly in pancreatic and lung cancers, where it may act as a tumor suppressor or oncogene depending on context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Moyamoya disease 2 | Loss-of-function mutations (e.g., p.R4810K) impair ubiquitin ligase activity, leading to abnormal vascular remodeling and intimal thickening. | ClinVar, OMIM |
| Intracranial aneurysm | RNF213 variants increase susceptibility to intracranial aneurysms, possibly through altered endothelial function. | ClinVar, PubMed |
| Pancreatic cancer | Somatic mutations and copy number alterations in RNF213 are observed; may contribute to tumor progression via dysregulated ubiquitination. | COSMIC, PubMed |
| Lung cancer | RNF213 expression is altered in lung cancer; potential role in metastasis and drug resistance. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Lung | 8.5 | Medium |
| Pancreas | 7.8 | Medium |
| Spleen | 6.9 | Low |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 12.3 | High expression; relevant to vascular function |
| A549 (lung cancer) | 9.8 | Moderate expression; cancer-related |
| PANC-1 (pancreatic cancer) | 8.7 | Moderate expression; cancer-related |
| HEK293 | 7.2 | Low to moderate; used for overexpression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.R4810K (c.14429G>A) | Missense | ~1-2% in East Asian populations; founder variant | Loss of function; strongly associated with Moyamoya disease |
| p.R4810K (c.14429G>A) | Missense | ~1-2% in East Asian populations; founder variant | Loss of function; strongly associated with Moyamoya disease |
| p.R4810K (c.14429G>A) | Missense | ~1-2% in East Asian populations; founder variant | Loss of function; strongly associated with Moyamoya disease |
| p.R4810K (c.14429G>A) | Missense | ~1-2% in East Asian populations; founder variant | Loss of function; strongly associated with Moyamoya disease |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations, including p.R4810K, reduce E3 ligase activity, impairing ubiquitination of targets like HIF1A, leading to abnormal angiogenesis.
Gain of Function (GOF)
Some somatic mutations in cancer may confer oncogenic properties, but evidence is limited; no clear gain-of-function mechanism established.
Dominant Negative (DN)
Heterozygous mutations may exert dominant-negative effects by interfering with wild-type protein function in oligomeric complexes.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • ATP binding |
| • metal ion binding | • protein ubiquitination |
| • angiogenesis | • response to hypoxia |
| • signal transduction |
Pathways
• Ubiquitin-proteasome pathway
• HIF-1 signaling pathway
• VEGF signaling pathway
• Notch signaling pathway
Protein Summary
RNF213 is a 591 kDa protein with multiple domains: an N-terminal RING finger domain, a central AAA+ ATPase domain, and a C-terminal region with E3 ligase activity. It ubiquitinates target proteins, including HIF1A, to regulate angiogenesis and cellular stress responses. The protein is predominantly cytoplasmic but can translocate to the nucleus upon stimulation. Its large size and complex domain architecture suggest multiple functions in vascular homeostasis and immune regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF213 Knockout HEK293 Cell Line | EDJ-KQ2092 | Human | 57674 | Details Get a Quote |
| RNF213 Knockout A-549 Cell Line | EDJ-KQ22191 | Human | 57674 | Details Get a Quote |
| RNF213 Knockout HCT 116 Cell Line | EDJ-KQ22192 | Human | 57674 | Details Get a Quote |
| RNF213 Knockout HeLa Cell Line | EDJ-KQ22193 | Human | 57674 | Details Get a Quote |
| RNF213 Knockout hCMEC/D3 Cell Line | EDJ-KZ434 | Human | 57674 | Details Get a Quote |
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