RNF139 (Ring Finger Protein 139)
E3 ubiquitin-protein ligase involved in endoplasmic reticulum-associated degradation and tumor suppression
Gene Information Card
| Symbol | RNF139 |
|---|---|
| Full Name | Ring Finger Protein 139 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.13 |
| NCBI Gene ID | 11236 ncbi.nlm.nih.gov/gene/11236 |
| Ensembl ID | ENSG00000170852 |
| UniProt ID | Q8WU17 |
| OMIM ID | 603046 |
| HGNC ID | 17095 |
| Aliases | TRC8, HRC8, RNF139 |
Description
RNF139 encodes an E3 ubiquitin-protein ligase that localizes to the endoplasmic reticulum (ER) and is involved in ER-associated degradation (ERAD). It contains a RING finger domain, a sterol-sensing domain, and multiple transmembrane regions. The protein targets misfolded or excess proteins for ubiquitination and proteasomal degradation, and plays a role in cholesterol homeostasis and tumor suppression. Mutations in RNF139 are associated with hereditary renal cancer and other malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary renal cancer (including clear cell renal cell carcinoma) | Loss-of-function mutations impair ERAD and tumor suppression, leading to accumulation of oncogenic substrates | OMIM #603046; PMID: 15805163 |
| Papillary renal cell carcinoma | Somatic mutations and copy number alterations disrupt ubiquitin ligase activity | COSMIC; PMID: 21941004 |
| Prostate cancer | RNF139 downregulation correlates with poor prognosis; potential tumor suppressor role | PMID: 22952342 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Testis | 8.2 | Low |
| Liver | 6.1 | Low |
| Brain | 4.3 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | Embryonic kidney cell line |
| A549 | 7.5 | Lung carcinoma |
| HeLa | 6.2 | Cervical carcinoma |
| MCF7 | 4.1 | Breast carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.124C>T (p.Arg42*) | Nonsense | <1% | Loss of function; truncation of RING domain |
| c.287G>A (p.Arg96Gln) | Missense | <1% | Impaired ubiquitin ligase activity |
| c.523_524del (p.Leu175fs) | Frameshift | <1% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (nonsense, frameshift, missense in RING domain) reduce or abolish E3 ligase activity, impairing ERAD and tumor suppression.
Gain of Function (GOF)
No evidence for gain-of-function mutations in RNF139.
Dominant Negative (DN)
Not established; heterozygous germline mutations may act via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endoplasmic reticulum-associated degradation (ERAD) pathway
• Ubiquitin-proteasome system
• Cholesterol biosynthesis regulation
Protein Summary
RNF139 (TRC8) is a 664-amino acid transmembrane E3 ubiquitin ligase with a RING-H2 finger domain, a sterol-sensing domain, and multiple transmembrane helices. It resides in the ER membrane and mediates ubiquitination of substrates involved in ERAD, cholesterol sensing, and cell growth control. The protein interacts with VHL and other tumor suppressors, and its loss contributes to renal carcinogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF139 Knockout HEK293 Cell Line | EDJ-KQ1624 | Human | 11236 | Details Get a Quote |
| RNF139 Knockout A-549 Cell Line | EDJ-KQ22652 | Human | 11236 | Details Get a Quote |
| RNF139 Knockout HCT 116 Cell Line | EDJ-KQ22654 | Human | 11236 | Details Get a Quote |
| RNF139 Knockout HeLa Cell Line | EDJ-KQ22655 | Human | 11236 | Details Get a Quote |
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