RNF168
Chr 3ARring finger protein 168
Also known as: RIDL, hRNF168
RNF168 encodes an E3 ubiquitin ligase that is required for accumulating DNA repair proteins at sites of double-strand breaks and interstrand cross-links, promoting histone ubiquitination to recruit key repair factors like TP53BP1 and BRCA1. Biallelic mutations cause RIDDLE syndrome, an autosomal recessive disorder characterized by radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties. The gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
499 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 | 22 | 0 | 81 | 0 | 103 |
Likely Pathogenic | 11 | 0 | 2 | 0 | 13 |
VUS | 7 | 171 | 20 | 1 | 199 |
Likely Benign | 0 | 8 | 41 | 99 | 148 |
Benign | 0 | 7 | 3 | 3 | 13 |
Conflicting | — | 12 | |||
| Total | 40 | 186 | 147 | 103 | 488 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF168 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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