RNF220

Chr 1

ring finger protein 220

Also known as: C1orf164, HLD23

NCBI Gene: 55182ENSG00000187147UniProt: Q5VTB9

Enables beta-catenin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway and protein polyubiquitination. Acts upstream of or within positive regulation of transcription by RNA polymerase II and protein monoubiquitination. Located in nuclear lamina and nucleoplasm. Part of protein-containing complex. Implicated in hypomyelinating leukodystrophy 23. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
12
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
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GeneReview available — RNF220
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.20LOEUF
pLI 1.000
Z-score 4.84
OE 0.06 (0.03–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.22Z-score
OE missense 0.67 (0.60–0.74)
234 obs / 351.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.03–0.20)
0≤0.351.4
Missense OE?0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 2 / 31.1Missense obs/exp: 234 / 351.3Syn Z: 0.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients