RNF4

Chr 4

ring finger protein 4

Also known as: RES4-26, SLX5, SNURF

NCBI Gene: 6047ENSG00000063978UniProt: P78317

RNF4 encodes an E3 ubiquitin-protein ligase that targets polysumoylated proteins for proteasomal degradation and regulates chromosome alignment, spindle assembly, and cellular responses to stress. The gene is highly constrained against loss-of-function variants (LOEUF 0.49), but no established human disease associations have been reported in the provided data. Clinical significance of RNF4 variants in pediatric neurology remains to be determined.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
17
Pubs (1 yr)
131
P/LP submissions
0%
P/LP missense
0.49
LOEUF
—
Mechanism
Clinical Summary— RNF4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
131 unique Pathogenic / Likely Pathogenic· 42 VUS of 189 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.800
Z-score 2.58
OE 0.10 (0.04–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.07Z-score
OE missense 0.72 (0.60–0.86)
83 obs / 115.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.04–0.49)
0≤0.351.4
Missense OE0.72 (0.60–0.86)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 1 / 9.7Missense obs/exp: 83 / 115.4Syn Z: 0.10

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic5
VUS42
Likely Benign7
126
Pathogenic
5
Likely Pathogenic
42
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
126
0
126
Likely Pathogenic
0
0
5
0
5
VUS
0
30
12
0
42
Likely Benign
0
7
0
0
7
Benign
0
0
0
0
0
Total0371430180

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF4 · 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.

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Clinical Literature
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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
Development of the first-in-class RNF4 PROTAC degrader as potential therapeutics for hepatocellular carcinoma.
Wan H et al.·Eur J Med Chem
2026
Total Chemical Synthesis of RNF4 by Sequential Native Chemical Ligation: C-To-N Versus N-To-C Strategies.
Pallava R et al.·J Org Chem
2026Open Access
RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.
Jung E et al.·Nucleic Acids Res
2025Open Access
RING Finger Protein 4 (RNF4) Reduces Nonalcoholic Fatty Liver Disease Accumulation by Promoting the SUMOylation of HIF-2α and Regulating the PPARα Signaling Pathway.
Yang L et al.·IUBMB Life
2025
Low-dose lipopolysaccharide modulates the RNF4-induced SUMO-dependent degradation of Nrf2 to mitigate oxidative stress in spinal cord injury.
Liu W et al.·Naunyn Schmiedebergs Arch Pharmacol
2026
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