RNF6

Chr 13

ring finger protein 6

NCBI Gene: 6049ENSG00000127870UniProt: Q9Y252OMIM: 604242

RNF6 encodes an E3 ubiquitin-protein ligase that mediates polyubiquitination and proteasomal degradation of multiple proteins including LIMK1, androgen receptor, and QKI, thereby regulating axonal outgrowth and transcriptional activity. Mutations in this gene cause esophageal carcinoma with somatic inheritance pattern. The gene shows tolerance to loss-of-function variants (pLI = 0.014, LOEUF = 0.526), suggesting that complete loss of function may be compatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismLOEUF 0.531 OMIM phenotype
Clinical Summary— RNF6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 91 VUS of 140 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
0.53LOEUF
pLI 0.014
Z-score 3.53
OE 0.30 (0.18–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.25Z-score
OE missense 0.82 (0.75–0.90)
310 obs / 378.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.18–0.53)
0≤0.351.4
Missense OE0.82 (0.75–0.90)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 9 / 29.8Missense obs/exp: 310 / 378.3Syn Z: 0.37
DN
0.7229th %ile
GOF
0.3789th %ile
LOF
0.3940th %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

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic2
VUS91
Likely Benign8
Benign3
33
Pathogenic
2
Likely Pathogenic
91
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
30
0
33
Likely Pathogenic
0
0
2
0
2
VUS
0
87
4
0
91
Likely Benign
0
7
1
0
8
Benign
0
1
0
2
3
Total098372137

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF6 · 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