IKZF4 Gene

HGNC Family	Zinc fingers
Name	IKAROS family zinc finger 4 (Eos)
Description	Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IKZF4, also known as Eos, is a member of the Ikaros family of transcription factors that plays a pivotal role in immune regulation. In regulatory T cells (Tregs), IKZF4 functions as an obligate corepressor for Foxp3, thereby helping to maintain the Treg-specific transcriptional program and ensuring proper suppressor activity. Notably, under inflammatory conditions, the downregulation of IKZF4 in a specific “Eos-labile” subset permits Tregs to reprogram into helper‐like cells that support antigen presentation, thus influencing local immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, failure of proper interaction between Foxp3 and IKZF4—as observed in Foxp3 reporter models—leads to altered chromatin modifications, reduced Foxp3 activity, and diminished Treg function, which may predispose to autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic association studies further underscore the clinical significance of IKZF4. Genome‐wide investigations have linked variants in genomic regions encompassing IKZF4 with autoimmune conditions such as alopecia areata, suggesting that dysregulation of Treg cell activation and proliferation underlies disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, specific polymorphisms in the IKZF4 locus have been associated with altered autoantibody profiles in type 1 diabetes, implying that IKZF4 may modulate pathways of β‐cell autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although IKZF4 is best characterized for its critical role in Treg biology, complementary studies indicate that it also contributes to the regulation of conventional T cell activation, affecting interleukin‐2 production and cytokine profiles; these findings suggest that alterations in IKZF4 expression or function may broadly impact immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these data establish IKZF4 as an essential transcriptional regulator that both sustains Treg cell identity and modulates immune tolerance, while genetic disruptions at its locus contribute to the pathogenesis of autoimmune diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Madhav D Sharma, Lei Huang, Jeong-Hyeon Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2013.01.013"}], "href": "https://doi.org/10.1016/j.immuni.2013.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23684987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23684987"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Matthew L Bettini, Fan Pan, Maria Bettini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2012.03.020"}], "href": "https://doi.org/10.1016/j.immuni.2012.03.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22579476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22579476"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lynn Petukhova, Madeleine Duvic, Maria Hordinsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study in alopecia areata implicates both innate and adaptive immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09114"}], "href": "https://doi.org/10.1038/nature09114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20596022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20596022"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dagny Jagielska, Silke Redler, Felix F Brockschmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Follow-up study of the first genome-wide association scan in alopecia areata: IL13 and KIAA0350 as susceptibility loci supported with genome-wide significance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2012.129"}], "href": "https://doi.org/10.1038/jid.2012.129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22534877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22534877"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "J Lempainen, T Härkönen, Ap Laine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Associations of polymorphisms in non-HLA loci with autoantibodies at the diagnosis of type 1 diabetes: INS and IKZF4 associate with insulin autoantibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Diabetes (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/pedi.12046"}], "href": "https://doi.org/10.1111/pedi.12046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23721563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23721563"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sadiye Amcaoglu Rieder, Amina Metidji, Deborah Dacek Glass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eos Is Redundant for Regulatory T Cell Function but Plays an Important Role in IL-2 and Th17 Production by CD4+ Conventional T Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1500627"}], "href": "https://doi.org/10.4049/jimmunol.1500627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26062998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26062998"}]}]}]}
Synonyms	ZNFN1A4
Proteins	IKZF4_HUMAN
NCBI Gene ID	64375
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IKZF4 has 4,665 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 112 datasets.

Click the + buttons to view associations for IKZF4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IKZF4 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 IKZF4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IKZF4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IKZF4 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 IKZF4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IKZF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IKZF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with IKZF4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing IKZF4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of IKZF4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IKZF4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with IKZF4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IKZF4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving IKZF4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 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 IKZF4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IKZF4 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 IKZF4 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 IKZF4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IKZF4 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 IKZF4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with IKZF4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.