RNF20

Chr 9

ring finger protein 20

Also known as: BRE1, BRE1A, hBRE1

NCBI Gene: 56254ENSG00000155827UniProt: Q5VTR2OMIM: 607699

The protein functions as an E3 ubiquitin ligase that monoubiquitinates histone H2B at lysine 120, which is essential for transcriptional activation and prerequisite for histone H3 methylation, thereby playing a central role in epigenetic gene regulation and chromatin structure. Biallelic mutations in RNF20 cause a neurodevelopmental disorder with intellectual disability and developmental delay, following an autosomal recessive inheritance pattern. The pathogenic mechanism involves disruption of the histone code and transcriptional regulation, particularly affecting genes critical for normal neurodevelopment.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.61
Clinical Summary— RNF20
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 101 VUS of 166 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — RNF20
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.61LOEUF
pLI 0.000
Z-score 3.99
OE 0.45 (0.33–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
3.11Z-score
OE missense 0.63 (0.57–0.68)
343 obs / 548.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.45 (0.33–0.61)
0≤0.351.4
Missense OE0.63 (0.57–0.68)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 27 / 60.5Missense obs/exp: 343 / 548.1Syn Z: 0.70
DN
0.6841th %ile
GOF
0.4382th %ile
LOF
0.4825th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic2
VUS101
Likely Benign4
Benign1
Conflicting1
32
Pathogenic
2
Likely Pathogenic
101
VUS
4
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
2
0
2
VUS
0
98
3
0
101
Likely Benign
0
1
1
2
4
Benign
0
0
0
1
1
Conflicting
—1
Total099383141

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF20 · 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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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