RNF126 Gene

HGNC Family	Zinc fingers
Name	ring finger protein 126
Description	The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF126 plays a pivotal role in cellular protein quality control by functioning as an E3 ubiquitin ligase that ensures the proper fate of both mislocalized and aggregation‐prone proteins. It is recruited by the BAG6 complex to ubiquitinate proteins that fail to engage the secretory pathway (for example, mislocalized membrane proteins and the activation‐induced cytidine deaminase [AID]), thereby preventing their cytosolic aggregation. In addition, RNF126 contributes to proper endosomal sorting of membrane receptors, such as the epidermal growth factor receptor and the cation-independent mannose 6‑phosphate receptor, and reubiquitinates p97-extracted substrates in cooperation with BAG6."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n \nRobust DNA damage response (DDR) is another realm where RNF126 exerts considerable influence. It facilitates nonhomologous end joining by ubiquitinating the Ku80 subunit after double-strand break induction and supports homologous recombination by promoting BRCA1 expression via its interaction with the transcription factor E2F1. RNF126 further regulates checkpoint signaling through upregulation of CHEK1 transcription and by modulating the ubiquitination status of DDR regulators such as RNF168. In addition, posttranslational modification events—including PARP1-mediated poly(ADP)ribosylation—affect its stability and contribute to ATR–Chk1 pathway activation (which is critical in response to radiation or PARP inhibitors), partly through the ubiquitination of MRE11."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": "\n \nIn the context of disease, particularly cancer and other pathologies, RNF126 exhibits multifaceted oncogenic and regulatory functions. It targets cell cycle regulators, such as p21, for ubiquitin-mediated degradation to promote cell proliferation, while also diminishing tumor suppressors like PTEN and LKB1—thereby activating pro-survival pathways such as PI3K–AKT signaling in diverse cancers including bladder, tongue, hepatocellular, and lung adenocarcinoma. Moreover, its overexpression has been linked to poor clinical outcomes in breast, ovarian, gastric, and lung cancers, and it has been implicated in modulating sensitivity to targeted therapeutic agents (for instance, CHEK1 and ATR inhibitors). Beyond cancer, RNF126 also controls the stability of factors critical for mitochondrial function (such as frataxin) and energy production in cardiomyocytes via regulation of G0S2 turnover."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rebecca K Delker, Yanjiao Zhou, Alexandros Strikoudis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Solubility-based genetic screen identifies RING finger protein 126 as an E3 ligase for activation-induced cytidine deaminase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1214538110"}], "href": "https://doi.org/10.1073/pnas.1214538110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23277564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23277564"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christopher J Smith, Donna M Berry, C Jane McGlade "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of the epidermal growth factor receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.116129"}], "href": "https://doi.org/10.1242/jcs.116129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23418353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23418353"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christopher J Smith, C Jane McGlade "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase RNF126 regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2013.11.013"}], "href": "https://doi.org/10.1016/j.yexcr.2013.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24275455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24275455"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Monica C Rodrigo-Brenni, Erik Gutierrez, Ramanujan S Hegde "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.05.025"}], "href": "https://doi.org/10.1016/j.molcel.2014.05.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24981174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24981174"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ewelina M Krysztofinska, Santiago Martínez-Lumbreras, Arjun Thapaliya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional insights into the E3 ligase, RNF126."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep26433"}], "href": "https://doi.org/10.1038/srep26433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27193484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27193484"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xianyan Hu, Linhan Wang, Yuancai Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF126-Mediated Reubiquitination Is Required for Proteasomal Degradation of p97-Extracted Membrane Proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.06.023"}], "href": "https://doi.org/10.1016/j.molcel.2020.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32645369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32645369"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Y Wang, O Deng, Z Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.198"}], "href": "https://doi.org/10.1038/onc.2015.198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26234677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26234677"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Noriko Ishida, Tadashi Nakagawa, Shun-Ichiro Iemura, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RNF126 Quenches RNF168 Function in the DNA Damage Response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics Proteomics Bioinformatics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gpb.2018.07.004"}], "href": "https://doi.org/10.1016/j.gpb.2018.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30529286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30529286"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Wenjing Wu, Jianli Zhao, Jianhong Xiao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Sci (Weinh) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/advs.202203884"}], "href": "https://doi.org/10.1002/advs.202203884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36563124"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36563124"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xu Zhi, Dong Zhao, Zehua Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-0562"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-0562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23026136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23026136"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Lina Wang, Xin Wang, Yuehan Zhao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-022-00782-6"}], "href": "https://doi.org/10.1007/s13577-022-00782-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36068398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36068398"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "You Pan, Yuchao Yang, Rong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-022-01586-0"}], "href": "https://doi.org/10.1186/s13058-022-01586-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36539893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36539893"}]}]}]}
Proteins	RN126_HUMAN
NCBI Gene ID	55658
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNF126 has 5,489 functional associations with biological entities spanning 9 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, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for RNF126 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 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 RNF126 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF126 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 RNF126 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNF126 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RNF126 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RNF126 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNF126 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 RNF126 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 RNF126 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNF126 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNF126 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RNF126 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RNF126 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 RNF126 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RNF126 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RNF126 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RNF126 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 RNF126 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RNF126 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 RNF126 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 RNF126 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RNF126 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 RNF126 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 RNF126 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RNF126 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 RNF126 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 RNF126 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RNF126 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 RNF126 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RNF126 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of RNF126 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.