RNF139

Chr 8

ring finger protein 139

Also known as: HRCA1, RCA1, TRC8

NCBI Gene: 11236 ENSG00000170881 UniProt: Q8WU17

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.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a multi-membrane spanning protein containing a RING-H2 finger. This protein is located in the endoplasmic reticulum, and has been shown to possess ubiquitin ligase activity. This gene was found to be interrupted by a t(3:8) translocation in a family with hereditary renal and non-medulary thyroid cancer. Studies of the Drosophila counterpart suggested that this protein may interact with tumor suppressor protein VHL, as well as with COPS5/JAB1, a protein responsible for the degradation of tumor suppressor CDKN1B/P27KIP. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRenal cell carcinoma

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429