RNF25 Gene

HGNC Family	Zinc fingers
Name	ring finger protein 25
Description	The protein encoded by this gene contains a RING finger motif. The mouse counterpart of this protein has been shown to interact with Rela, the p65 subunit of NF-kappaB (NFKB), and modulate NFKB-mediated transcription activity. The mouse protein also binds ubiquitin-conjugating enzymes (E2s) and is a substrate for E2-dependent ubiquitination. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF25, also known as AO7, is a RING finger protein that plays a central role in modulating protein turnover via ubiquitination. Initially identified for its ability to bind ubiquitin‐conjugating enzymes (E2s) and serve as a substrate for E2‐dependent ubiquitination, its RING finger domain is essential for catalytic activity—as mutations in its cation‐coordinating residues or zinc chelation abolish function. In addition, RNF25 interacts with the p65 (RelA) subunit of NF‑κB through a critical C‑terminal region, thereby regulating NF‑κB–dependent transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural investigations have uncovered that RNF25 contains a distinctive E2-binding module known as the U5BR, which is connected via a short linker to its RING domain. This unique clamp-like structure envelops the E2 enzyme UbcH5B, enabling high-affinity binding that, while reducing the stimulatory non-covalent ubiquitin binding at the backside of UbcH5B, intricately regulates the rate of ubiquitination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn disease contexts, RNF25 has emerged as a pivotal mediator in cancer progression and drug resistance. In non-small cell lung cancer (NSCLC), RNF25 contributes to gefitinib resistance by promoting NF‑κB activation, which drives ERK pathway reactivation through the induction of cytokines such as IL‑6. In parallel, in hepatocellular carcinoma (HCC), oxidative stress triggers protein kinase A (PKA) to phosphorylate RNF25, thereby initiating the degradation of E-cadherin and facilitating tumor metastasis. Collectively, these findings position RNF25 as a critical regulator linking ubiquitination, transcriptional control, and oncogenic signaling pathways, highlighting its potential as a novel therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K L Lorick, J P Jensen, S Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.96.20.11364"}], "href": "https://doi.org/10.1073/pnas.96.20.11364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10500182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10500182"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kaori Asamitsu, Toshifumi Tetsuka, Satoshi Kanazawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RING finger protein AO7 supports NF-kappaB-mediated transcription by interacting with the transactivation domain of the p65 subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M211831200"}], "href": "https://doi.org/10.1074/jbc.M211831200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12748188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12748188"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shengjian Li, Yu-He Liang, Jennifer Mariano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights into Ubiquitination from the Unique Clamp-like Binding of the RING E3 AO7 to the E2 UbcH5B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.685867"}], "href": "https://doi.org/10.1074/jbc.M115.685867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26475854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26475854"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jung Hee Cho, Yeon-Mi You, Y I Yeom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0651-5"}], "href": "https://doi.org/10.1038/s41419-018-0651-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29789542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29789542"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhao Huang, Li Zhou, Jiufei Duan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative Stress Promotes Liver Cancer Metastasis via RNF25-Mediated E-Cadherin Protein Degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Sci (Weinh) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/advs.202306929"}], "href": "https://doi.org/10.1002/advs.202306929"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38286671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38286671"}]}]}]}
Synonyms	AO7
Proteins	RNF25_HUMAN
NCBI Gene ID	64320
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RNF25 has 5,307 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 111 datasets.

Click the + buttons to view associations for RNF25 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RNF25 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 RNF25 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RNF25 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RNF25 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 RNF25 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RNF25 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 RNF25 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RNF25 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RNF25 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 RNF25 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RNF25 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RNF25 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RNF25 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RNF25 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RNF25 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 RNF25 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 RNF25 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RNF25 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RNF25 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 RNF25 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 RNF25 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 RNF25 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 RNF25 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RNF25 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 RNF25 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RNF25 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 RNF25 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 RNF25 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RNF25 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.