RNF213
Chr 17ADARring finger protein 213
Also known as: ALO17, C17orf27, KIAA1618, MYMY2, MYSTR, NET57
The protein functions as an atypical E3 ubiquitin ligase with ATPase activity that catalyzes ubiquitination of both proteins and lipids, playing roles in lipid metabolism, angiogenesis, cell-autonomous immunity, and vascular development through the non-canonical Wnt signaling pathway. Mutations cause susceptibility to Moyamoya disease, a vascular disorder affecting intracranial arteries, with both autosomal dominant and autosomal recessive inheritance patterns reported. The pathogenic mechanism involves dominant-negative effects that likely disrupt the protein's critical ubiquitin ligase and ATPase functions.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
898 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 5 | 10 | 0 | 15 |
Likely Pathogenic | 2 | 9 | 1 | 0 | 12 |
VUS | 8 | 289 | 46 | 2 | 345 |
Likely Benign | 1 | 74 | 45 | 151 | 271 |
Benign | 1 | 53 | 30 | 63 | 147 |
Conflicting | — | 26 | |||
| Total | 12 | 430 | 132 | 216 | 816 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF213 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools