RNF139

Chr 8

ring 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOEUF 0.441 OMIM phenotype
Clinical SummaryRNF139
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.54) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.538
Z-score 3.59
OE 0.21 (0.110.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.84Z-score
OE missense 0.73 (0.660.81)
261 obs / 359.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.110.44)
00.351.4
Missense OE0.73 (0.660.81)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 5 / 24.0Missense obs/exp: 261 / 359.2Syn Z: -0.89

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC