IREB2 Gene

Name	iron-responsive element binding protein 2
Description	The protein encoded by this gene is an RNA-binding protein that acts to regulate iron levels in the cells by regulating the translation and stability of mRNAs that affect iron homeostasis under conditions when iron is depleted. When iron levels are low, this protein binds to iron-responsive elements (IRES), stem-loop structures located either in the 5' or 3' UTRs. Binding to the 5' UTR represses translation, while binding to the 3' UTR inhibits mRNA degradation. When iron is found in the cell, this protein is degraded in a F-box and leucine rich repeat protein 5-dependent manner. Variants in this gene have been associated with lung cancer and chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IREB2, which encodes iron‐regulatory protein 2 (IRP2), is a central post‐transcriptional regulator of cellular iron homeostasis that modulates the expression of key proteins involved in iron uptake, storage, and distribution—most notably the transferrin receptor and ferritin messenger RNAs through binding to iron‐responsive elements (IREs)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In iron‐ and oxygen‐replete conditions, IRP2 is selectively targeted for degradation by an SCF ubiquitin ligase complex involving FBXL5, whose iron‐binding hemerythrin‐like domain serves as a critical sensor; this post‐translational regulation ensures that IRP2 levels accurately reflect intracellular iron availability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Genetic ablation studies in mice demonstrate that loss of IRP2 leads to widespread misregulation of iron metabolism—including defects in erythropoiesis that result in microcytic anemia and aberrant iron distribution across the liver, spleen, and bone marrow—thereby underscoring its dominant physiological role relative to IRP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Genetic association studies have further implicated IREB2 in chronic obstructive pulmonary disease (COPD), with several single-nucleotide polymorphisms in the IREB2 locus correlating with reduced lung function and airflow obstruction; supporting experimental models suggest that IRP2-mediated increases in mitochondrial iron loading and altered cytochrome c oxidase levels may contribute to COPD pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": " Moreover, FBXL5 deficiency—which impairs the normal, iron‐dependent degradation of IRP2—can lead to embryonic lethality that is rescued upon concomitant IRP2 ablation, emphasizing the importance of balanced IRP2 turnover for systemic iron equilibrium."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, emerging evidence indicates that components of the cytosolic iron–sulfur cluster assembly (CIA) machinery can influence IRP2 stability, thereby linking iron–sulfur protein biogenesis with the regulation of cellular iron flux."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these studies establish IRP2 as an essential iron sensor and regulator that integrates intracellular iron signals and couples iron homeostasis to disease processes such as anemia, neurodegeneration, and COPD.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Esther G Meyron-Holtz, Manik C Ghosh, Kazuhiro Iwai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600041"}], "href": "https://doi.org/10.1038/sj.emboj.7600041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14726953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14726953"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ajay A Vashisht, Kimberly B Zumbrennen, Xinhua Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of iron homeostasis by an iron-regulated ubiquitin ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1176333"}], "href": "https://doi.org/10.1126/science.1176333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19762596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19762596"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ameen A Salahudeen, Joel W Thompson, Julio C Ruiz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1176326"}], "href": "https://doi.org/10.1126/science.1176326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19762597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19762597"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Eric S Hanson, Mindy L Rawlins, Elizabeth A Leibold "}, {"type": "b", "children": [{"type": "t", "text": "Oxygen and iron regulation of iron regulatory protein 2."}]}, {"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.M302798200"}], "href": "https://doi.org/10.1074/jbc.M302798200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12888568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12888568"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sharon S Cooperman, Esther G Meyron-Holtz, Hayden Olivierre-Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-12-4703"}], "href": "https://doi.org/10.1182/blood-2004-12-4703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15831703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15831703"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bruno Galy, Dunja Ferring, Belen Minana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-04-1365"}], "href": "https://doi.org/10.1182/blood-2005-04-1365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15956281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15956281"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Suzanne M Cloonan, Kimberly Glass, Maria E Laucho-Contreras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4021"}], "href": "https://doi.org/10.1038/nm.4021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26752519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26752519"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alex D Sheftel, Claudia Wilbrecht, Oliver Stehling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-09-0772"}], "href": "https://doi.org/10.1091/mbc.E11-09-0772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22323289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22323289"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Dawn L DeMeo, Thomas Mariani, Soumyaroop Bhattacharya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.09.004"}], "href": "https://doi.org/10.1016/j.ajhg.2009.09.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19800047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19800047"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sreekumar G Pillai, Xiangyang Kong, Lisa D Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.201002-0151OC"}], "href": "https://doi.org/10.1164/rccm.201002-0151OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20656943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20656943"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Toshiro Moroishi, Masaaki Nishiyama, Yukiko Takeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2011.07.011"}], "href": "https://doi.org/10.1016/j.cmet.2011.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21907140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21907140"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Oliver Stehling, Judita Mascarenhas, Ajay A Vashisht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2013.06.015"}], "href": "https://doi.org/10.1016/j.cmet.2013.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23891004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23891004"}]}]}]}
Synonyms	IRP2AD, IRE-BP2, ACO3, IRP2, IRE-BP 2
Proteins	IREB2_HUMAN
NCBI Gene ID	3658
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IREB2 has 7,343 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

Click the + buttons to view associations for IREB2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IREB2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IREB2 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 IREB2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IREB2 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 IREB2 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 IREB2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing IREB2 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 IREB2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IREB2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IREB2 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 IREB2 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 IREB2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IREB2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IREB2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with IREB2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of IREB2 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 IREB2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate IREB2 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving IREB2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with IREB2 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 IREB2 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 IREB2 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 IREB2 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 IREB2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IREB2 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 IREB2 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 IREB2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IREB2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.