RC3H2 Gene

HGNC Family	Zinc fingers
Name	ring finger and CCCH-type domains 2
Description	Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRC3H2 is a member of the Roquin family of proteins that integrates RNA binding with E3 ubiquitin ligase activity to regulate mRNA stability. In one study, depletion of the mRNA decay factor roquin2 (RC3H2) by KLHL6-mediated ubiquitination was shown to promote oncogenic growth, illustrating how perturbations in RC3H2 regulation can influence cellular survival and tumor suppressor pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHigh-resolution structural analyses of RC3H2 have revealed that its RNA-binding region is composed of a bipartite architecture formed by the ROQ and HEPN domains. These studies demonstrated that RC3H2 can simultaneously engage with stem-loop and double-stranded RNAs, undergoing large conformational changes to facilitate RNA duplex binding. In parallel, biochemical profiling identified that RC3H2 interacts with a distinct set of E2 ubiquitin-conjugating enzymes, which enables the assembly of polyubiquitin chains with varied linkages, thereby coupling RNA recognition to ubiquitin ligase function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther crystallographic work on the ROQ domain of Roquin proteins has provided insights into the mechanism of mRNA recognition. The domain folds into a winged-helix structure with a flexible lid that accommodates binding to constitutive-decay elements within the 3′ untranslated regions of target mRNAs. Specific interactions, primarily with the phosphate backbone of the RNA, facilitate direct and water-mediated contacts that ensure selective mRNA degradation. These findings underscore a conserved mechanism by which RC3H2, along with its paralogs, modulates RNA homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in mRNA decay, RC3H2 has emerged as a potent regulator of tumor angiogenesis. By binding to stem-loop structures in the 3′UTRs of proangiogenic gene transcripts—such as endoglin, endothelin-1, VEGFB, and PDGFC—RC3H2 promotes their mRNA destabilization. This targeted downregulation of angiogenic factors not only inhibits tumor-induced blood vessel formation but also correlates with improved clinical outcomes in breast cancer, positioning RC3H2 as a novel tumor suppressor in the angiogenesis pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jaewoo Choi, Kyutae Lee, Kristin Ingvarsdottir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of KLHL6 promotes diffuse large B-cell lymphoma growth and survival by stabilizing the mRNA decay factor roquin2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-018-0084-5"}], "href": "https://doi.org/10.1038/s41556-018-0084-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29695787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29695787"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qi Zhang, Lixin Fan, Feng Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep15660"}], "href": "https://doi.org/10.1038/srep15660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26489670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26489670"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shunya Sakurai, Umeharu Ohto, Toshiyuki Shimizu "}, {"type": "b", "children": [{"type": "t", "text": "Structure of human Roquin-2 and its complex with constitutive-decay element RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr F Struct Biol Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S2053230X15011887"}], "href": "https://doi.org/10.1107/S2053230X15011887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26249698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26249698"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meicen Zhou, Wenbao Lu, Bingwei Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roquin2 suppresses breast cancer progression by inhibiting tumor angiogenesis via selectively destabilizing proangiogenic factors mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.59891"}], "href": "https://doi.org/10.7150/ijbs.59891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34345214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34345214"}]}]}]}
Synonyms	MNAB, RNF164
Proteins	RC3H2_HUMAN
NCBI Gene ID	54542
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RC3H2 has 4,865 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 108 datasets.

Click the + buttons to view associations for RC3H2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RC3H2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by RC3H2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RC3H2 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 RC3H2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RC3H2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RC3H2 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 RC3H2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RC3H2 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 RC3H2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RC3H2 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 RC3H2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RC3H2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RC3H2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RC3H2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RC3H2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by RC3H2 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 RC3H2 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 RC3H2 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 RC3H2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RC3H2 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 RC3H2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RC3H2 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 RC3H2 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 RC3H2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing RC3H2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RC3H2 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 RC3H2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of RC3H2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RC3H2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.