RNF220
Chr 1ARring finger protein 220
Also known as: C1orf164, HLD23
This E3 ubiquitin ligase regulates Wnt signaling through beta-catenin stabilization and plays a critical role in nuclear lamina regulation. Biallelic mutations cause autosomal recessive hypomyelinating leukodystrophy 23, a multisystem disorder involving ataxia, deafness, liver dysfunction, and dilated cardiomyopathy. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.20), indicating intolerance to protein disruption.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RNF220 · 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