RNF139 Gene

HGNC Family	Zinc fingers
Name	ring finger protein 139
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF139, also known as TRC8, has been implicated as a tumor‐suppressive factor in several cancers. In familial and sporadic renal carcinomas, disruption of RNF139 due to chromosomal translocations results in loss of the normal allele and contributes to tumor development. Similarly, reduced RNF139 expression has been observed in tongue cancer cells, where its lower levels are associated with enhanced malignant behavior, while in glioma, enforced expression of RNF139 suppresses proliferation, migration, and invasion—partly through attenuation of PI3K/AKT signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its tumor‐suppressive roles, RNF139 functions as an endoplasmic reticulum–resident E3 ubiquitin ligase that governs lipid and protein homeostasis. It modulates the processing of sterol regulatory element–binding proteins (SREBPs) through direct interactions with SREBP-2 and SCAP, thereby suppressing the expression of cholesterol and fatty acid biosynthetic genes. RNF139 also targets key proteins for degradation—such as heme oxygenase-1 (HO-1), misfolded or tail-anchored proteins, and even the cardiac hERG potassium channel—via ubiquitination processes that are regulated by sterol levels and other quality control mechanisms. Moreover, cooperation with proteins like INSIG1 further extends its capacity to regulate the turnover of viral proteins, emphasizing its central role in coordinating biosynthetic and degradative pathways at the ER."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRNF139 also plays a pivotal role in endoplasmic reticulum–associated protein degradation (ERAD) pathways that are exploited by viruses to evade immune detection. In the context of human cytomegalovirus infection, viral proteins such as US2 and US11 co-opt RNF139 to mediate the ubiquitination and dislocation of major histocompatibility complex class I molecules from the ER, thereby reducing their cell-surface expression; this process underlies an important viral immune evasion strategy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Brauweiler, K L Lorick, J P Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1210017"}], "href": "https://doi.org/10.1038/sj.onc.1210017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17016439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17016439"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kathryn S Poland, Mohammed Azim, Matthew Folsom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20466"}], "href": "https://doi.org/10.1002/gcc.20466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17539022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17539022"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lina Wang, Wei Yin, Chun Shi "}, {"type": "b", "children": [{"type": "t", "text": "E3 ubiquitin ligase, RNF139, inhibits the progression of tongue cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-017-3438-7"}], "href": "https://doi.org/10.1186/s12885-017-3438-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28662643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28662643"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaofeng Chen, Weiping Kuang, Yong Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An E3 Ubiquitin Ligase RNF139 Serves as a Tumor-Suppressor in Glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-021-01860-4"}], "href": "https://doi.org/10.1007/s12031-021-01860-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34106407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34106407"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masato Irisawa, Jun Inoue, Nozomi Ozawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.041376"}], "href": "https://doi.org/10.1074/jbc.M109.041376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19706601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19706601"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jason P Lee, Anne Brauweiler, Michael Rudolph, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-08-0491"}], "href": "https://doi.org/10.1158/1541-7786.MCR-08-0491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20068067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20068067"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "P-H Lin, W-M Lan, L-Y Chau "}, {"type": "b", "children": [{"type": "t", "text": "TRC8 suppresses tumorigenesis through targeting heme oxygenase-1 for ubiquitination and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.244"}], "href": "https://doi.org/10.1038/onc.2012.244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22689053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22689053"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Christine Hantouche, Brittany Williamson, William C Valinsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.752618"}], "href": "https://doi.org/10.1074/jbc.M116.752618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27998983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27998983"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sandra Stefanovic-Barrett, Anna S Dickson, Stephen P Burr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201745603"}], "href": "https://doi.org/10.15252/embr.201745603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29519897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29519897"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "You Zhang, Jing Lu, Jing Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insulin-induced gene 1 (INSIG1) inhibits HIV-1 production by degrading Gag via activity of the ubiquitin ligase TRC8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.004630"}], "href": "https://doi.org/10.1074/jbc.RA118.004630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30563842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30563842"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Helen R Stagg, Mair Thomas, Dick van den Boomen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200906110"}], "href": "https://doi.org/10.1083/jcb.200906110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19720873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19720873"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "D J H van den Boomen, P J Lehner "}, {"type": "b", "children": [{"type": "t", "text": "Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2015.07.005"}], "href": "https://doi.org/10.1016/j.molimm.2015.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26210183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26210183"}]}]}]}
Synonyms	TRC8
Proteins	RN139_HUMAN
NCBI Gene ID	11236
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNF139 has 6,145 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for RNF139 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNF139 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RNF139 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of RNF139 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of RNF139 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of RNF139 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of RNF139 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RNF139 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of RNF139 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RNF139 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RNF139 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of RNF139 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF139 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of RNF139 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNF139 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RNF139 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNF139 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of RNF139 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RNF139 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNF139 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNF139 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RNF139 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with RNF139 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF139 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RNF139 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RNF139 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RNF139 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RNF139 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by RNF139 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RNF139 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RNF139 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with RNF139 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with RNF139 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RNF139 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RNF139 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RNF139 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RNF139 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing RNF139 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RNF139 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RNF139 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing RNF139 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RNF139 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.