RNF139
Chr 8ring finger protein 139
Also known as: HRCA1, RCA1, TRC8
The RNF139 protein is an E3 ubiquitin ligase located in the endoplasmic reticulum that regulates cell proliferation, MHC class I processing, and cholesterol metabolism through targeted protein degradation. Mutations cause autosomal dominant renal cell carcinoma, with the gene showing high constraint against loss-of-function variants (LOEUF 0.438). The cancer predisposition involves both renal and non-medullary thyroid malignancies.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
130 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 52 | 0 | 52 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 69 | 6 | 0 | 75 |
Likely Benign | 0 | 0 | 0 | 1 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 69 | 58 | 1 | 128 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF139 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools