NFE2L3 Gene

HGNC Family	Basic leucine zipper proteins
Name	nuclear factor, erythroid 2-like 3
Description	This gene encodes a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. The encoded protein heterodimerizes with small musculoaponeurotic fibrosarcoma factors to bind antioxidant response elements in target genes. This protein is a membrane bound glycoprotein that is targeted to the endoplasmic reticulum and the nuclear envelope. Pseudogenes of this gene are found on chromosomes 16, 17, and 18. [provided by RefSeq, Mar 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNFE2L3, a member of the cap ’n’ collar (CNC) basic‐leucine zipper transcription factor family, functions as both a potent transcriptional activator and a context‐dependent repressor. It regulates expression of genes with antioxidant-response elements by dimerizing with small Maf proteins, and its activity is dynamically controlled through rapid turnover, N-glycosylation, and targeted ubiquitination mediated by kinases (e.g., GSK3) and the FBW7 E3 ligase complex. These post-translational modifications ensure that NFE2L3 levels are stringently adjusted in response to cellular stress and inflammation."}, {"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": "\nGenetic association studies have implicated NFE2L3 in non-cancerous physiological processes as well. For example, large-scale genome-wide meta-analyses have identified loci near NFE2L3 that associate with waist-hip ratio and body fat distribution independent of overall adiposity, suggesting a role in metabolic homeostasis. In addition, early developmental studies have demonstrated high expression of this transcription factor in tissues such as the placenta, and its regulation by inflammatory mediators (e.g., via TNF-α signaling) underscores a potential function in developmental and stress-response pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, dysregulation of NFE2L3 has been recurrently observed across diverse tumor types—including colon, pancreatic, hepatocellular, gastric, bladder, renal, esophageal, and triple-negative breast cancers—with its aberrant expression often correlating with enhanced cell proliferation, invasion, and metastasis. Upregulation of NFE2L3 occurs via mechanisms such as β-catenin/TCF-mediated transcription and DNA hypomethylation, which drive oncogenic programs by modulating key cell cycle regulators (e.g., UHMK1, CDK1, CCND1) and promoting epithelial–mesenchymal transition. Moreover, by inducing factors like POMP, NFE2L3 enhances the assembly of 20S proteasomes, contributing to ubiquitin-independent degradation of tumor suppressor proteins such as p53 and Rb. Interestingly, while its overexpression generally supports tumor progression and correlates with poor clinical outcome in most cancers, in the skin NFE2L3 appears to serve a tumor-suppressive role, highlighting its context-dependent functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kannan Sankaranarayanan, Anil K Jaiswal "}, {"type": "b", "children": [{"type": "t", "text": "Nrf3 negatively regulates antioxidant-response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404984200"}], "href": "https://doi.org/10.1074/jbc.M404984200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15385560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15385560"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Benoît Chénais, Anna Derjuga, Wael Massrieh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional and placental expression analysis of the human NRF3 transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2003-0379"}], "href": "https://doi.org/10.1210/me.2003-0379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15388789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15388789"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zaynab Nouhi, Grégory Chevillard, Anna Derjuga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endoplasmic reticulum association and N-linked glycosylation of the human Nrf3 transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.10.041"}], "href": "https://doi.org/10.1016/j.febslet.2007.10.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17976382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17976382"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meenakshi B Kannan, Isadore Dodard-Friedman, Volker Blank "}, {"type": "b", "children": [{"type": "t", "text": "Stringent Control of NFE2L3 (Nuclear Factor, Erythroid 2-Like 3; NRF3) Protein Degradation by FBW7 (F-box/WD Repeat-containing Protein 7) and Glycogen Synthase Kinase 3 (GSK3)."}]}, {"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.M115.666446"}], "href": "https://doi.org/10.1074/jbc.M115.666446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26306035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26306035"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Iris M Heid, Anne U Jackson, Joshua C Randall, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384047.2024.2416221"}], "href": "https://doi.org/10.1080/15384047.2024.2416221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39443820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39443820"}]}]}]}
Synonyms	NRF3
Proteins	NF2L3_HUMAN
NCBI Gene ID	9603
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NFE2L3 has 6,301 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 105 datasets.

Click the + buttons to view associations for NFE2L3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NFE2L3 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 NFE2L3 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 NFE2L3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NFE2L3 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 NFE2L3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NFE2L3 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 NFE2L3 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 NFE2L3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NFE2L3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NFE2L3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NFE2L3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NFE2L3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NFE2L3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NFE2L3 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 NFE2L3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with NFE2L3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NFE2L3 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 NFE2L3 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 NFE2L3 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 NFE2L3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NFE2L3 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 NFE2L3 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 NFE2L3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NFE2L3 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 NFE2L3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NFE2L3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NFE2L3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NFE2L3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NFE2L3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.