RNF222

Chr 17

ring finger protein 222

NCBI Gene: 643904ENSG00000189051UniProt: A6NCQ9

The protein is predicted to bind zinc ions and localize to cellular membranes, but its specific biological function remains unclear. No established human diseases have been definitively associated with RNF222 mutations. This gene appears to be tolerant to loss-of-function variants based on population genetic data.

ResearchSummary from RefSeq
GOFmechanismLOEUF 1.86
Clinical Summary— RNF222
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 55 VUS of 70 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.86LOEUF
pLI 0.000
Z-score -0.21
OE 1.11 (0.56–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.58Z-score
OE missense 0.86 (0.73–1.00)
109 obs / 127.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.11 (0.56–1.86)
0≤0.351.4
Missense OE0.86 (0.73–1.00)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 5 / 4.5Missense obs/exp: 109 / 127.5Syn Z: 1.10
DN
0.5966th %ile
GOF
0.71top 25%
LOF
0.3941th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS55
Likely Benign2
12
Pathogenic
55
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
49
6
0
55
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total05118069

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RNF222 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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