RNF208

Chr 9

ring finger protein 208

NCBI Gene: 727800ENSG00000212864UniProt: Q9H0X6OMIM: 618993

RNF208 encodes a ubiquitin-protein transferase that catalyzes protein autoubiquitination and localizes to the cytosol and nucleoplasm. The gene is highly constrained against loss-of-function variants (pLI 0.83, LOEUF 0.51), suggesting that mutations would likely cause severe developmental disorders. However, no specific disease associations or inheritance patterns have been established for RNF208 mutations in humans.

OMIMResearchSummary from RefSeq
GOFmechanismLOEUF 0.51
Clinical Summary— RNF208
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
95 unique Pathogenic / Likely Pathogenic· 57 VUS of 156 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.830
Z-score 2.24
OE 0.00 (0.00–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.24Z-score
OE missense 0.73 (0.63–0.85)
120 obs / 164.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.51)
0≤0.351.4
Missense OE0.73 (0.63–0.85)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 0 / 5.8Missense obs/exp: 120 / 164.8Syn Z: -1.88
DN
0.3892th %ile
GOF
0.6540th %ile
LOF
0.62top 25%

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

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic7
VUS57
Benign1
Conflicting3
88
Pathogenic
7
Likely Pathogenic
57
VUS
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
88
0
88
Likely Pathogenic
0
0
7
0
7
VUS
0
49
8
0
57
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Conflicting
—3
Total0491040156

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF208 · 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 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
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