RNF185

Chr 22

ring finger protein 185

NCBI Gene: 91445ENSG00000138942UniProt: Q96GF1

Enables ubiquitin binding activity; ubiquitin protein ligase activity; and ubiquitin-like protein conjugating enzyme binding activity. Involved in several processes, including positive regulation of ERAD pathway; protein ubiquitination; and proteolysis involved in protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

54
ClinVar variants
18
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— RNF185
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 21 VUS of 54 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.177
Z-score 2.18
OE 0.28 (0.13–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.05Z-score
OE missense 0.72 (0.60–0.87)
81 obs / 112.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.13–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.60–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 3 / 10.7Missense obs/exp: 81 / 112.4Syn Z: -0.37

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS21
Benign1
17
Pathogenic
1
Likely Pathogenic
21
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
19
2
0
21
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total01920140

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF185 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
RNF185 promotes esophageal squamous cell carcinoma progression by regulating BAK1 ubiquitination and activating the cGAS-STING-IRF3 pathway.
Wang KH et al.·Eur J Med Res
2025🔓 Open Access
Tapasin assembly surveillance by the RNF185/Membralin ubiquitin ligase complex regulates MHC-I surface expression.
van de Weijer ML et al.·Nat Commun
2024🔓 Open Access
Senecavirus A induces mitophagy to promote self-replication through direct interaction of 2C protein with K27-linked ubiquitinated TUFM catalyzed by RNF185.
Chen M et al.·Autophagy
2024
D-mannose promotes the degradation of IDH2 through upregulation of RNF185 and suppresses breast cancer.
Zhang R et al.·Nutr Metab (Lond)
2024🔓 Open Access
RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential.
Van Espen B et al.·Mol Cancer Res
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools