RNF31 Gene

HGNC Family	Zinc fingers
Name	ring finger protein 31
Description	The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The encoded protein is the E3 ubiquitin-protein ligase component of the linear ubiquitin chain assembly complex. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF31, also known as HOIP, is an atypical RING-type E3 ubiquitin ligase that forms the catalytic core of the linear ubiquitin chain assembly complex (LUBAC). In response to proinflammatory stimuli such as interleukin‑1, TNF‑α, and Toll-like receptor agonists, RNF31 mediates the formation of Met1‑linked (linear) polyubiquitin chains that are essential for robust NF‑κB activation and downstream immune signaling. This function is achieved through its dynamic interaction with other LUBAC components—including HOIL‑1L and SHARPIN—and regulators such as OTULIN and SPATA2, which together ensure proper assembly and disassembly of ubiquitin chains to modulate receptor‐proximal signaling events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, RNF31 has emerged as a critical modulator of tumor cell behavior. Specific germline polymorphisms in RNF31 increase its association with binding partners (such as RBCK1), which in turn augments LUBAC activity and NF‑κB signalling—a mechanism that has been implicated in the survival of activated B cell–like diffuse large B‑cell lymphoma. In breast cancer cells, RNF31 not only stabilizes estrogen receptor α via non‑genomic mechanisms but also promotes the polyubiquitination and degradation of p53 by stabilizing the p53/MDM2 complex. These activities are associated with enhanced cell proliferation, impaired cell cycle checkpoints, and tumor progression. Furthermore, elevated RNF31 expression has been correlated with aggressive hepatocellular carcinoma phenotypes and poor patient survival, underscoring its potential as a prognostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in immune signalling and tumorigenesis, RNF31 participates in finely tuned regulatory networks through its interactions with transcriptional coregulators and via post‑translational modifications. For instance, RNF31 forms part of a corepressor complex with DAX‑1 to modulate steroidogenic gene expression, and it promotes the stability of FOXP3 in regulatory T cells through atypical ubiquitin chain conjugation—thereby impacting immune tolerance and cancer immunosurveillance. Structural and biophysical studies have delineated key domains within RNF31 (including its PUB and UBA regions), which are critical for binding partners and for the regulation of its E3 ligase function. In addition, RNF31 is subject to regulatory proteolysis by caspases and other modifications that alter its catalytic activity, reflecting a sophisticated level of control that links cell survival and apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Judith J Smit, Davide Monteferrario, Sylvie M Noordermeer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2012.217"}], "href": "https://doi.org/10.1038/emboj.2012.217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22863777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22863777"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christoph H Emmerich, Alban Ordureau, Sam Strickson, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "--LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20160041"}], "href": "https://doi.org/10.1084/jem.20160041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27810922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27810922"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hirotsugu Oda, David B Beck, Hye Sun Kuehn, et al. 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Synonyms	HOIP, ZIBRA, Paul
Proteins	RNF31_HUMAN
NCBI Gene ID	55072
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNF31 has 6,069 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 116 datasets.

Click the + buttons to view associations for RNF31 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNF31 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 RNF31 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 RNF31 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 RNF31 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 RNF31 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 RNF31 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 RNF31 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 RNF31 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 RNF31 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 RNF31 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF31 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 RNF31 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNF31 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RNF31 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 RNF31 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNF31 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 RNF31 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RNF31 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RNF31 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RNF31 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RNF31 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNF31 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNF31 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RNF31 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 RNF31 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 RNF31 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RNF31 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RNF31 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by RNF31 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 RNF31 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 RNF31 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 RNF31 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 RNF31 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RNF31 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 RNF31 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 RNF31 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RNF31 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 RNF31 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 RNF31 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RNF31 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 RNF31 from the GeneSigDB Published Gene Signatures dataset.