ZBTB25 Gene

HGNC Family	BTB (POZ) domain containing (BTBD), Zinc fingers
Name	zinc finger and BTB domain containing 25
Description	Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZBTB25 is a BTB‐POZ family transcription factor that is highly enriched in T cells, where it functions as a negative regulator of the nuclear factor of activated T cells (NF‑AT) pathway. Its targeted knockdown has been shown to enhance the expression of NF‑AT target genes, suggesting that ZBTB25 plays a crucial role in modulating T‑cell activation, differentiation, and overall immune function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of influenza A virus (IAV) infection, ZBTB25 serves a proviral role. It enhances viral RNA synthesis through dual mechanisms: by interacting directly with the viral RNA‐dependent RNA polymerase and by binding preferentially to the U‑rich region within the 5′ untranslated region of the viral RNA. Additionally, ZBTB25 suppresses interferon production, thereby facilitating IAV replication, and its zinc finger domain (subject to posttranslational SUMO‑1 modification) is essential for these functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDuring Mycobacterium tuberculosis infection, ZBTB25 is recruited as a key component of an HDAC1/Sin3a repressor complex in macrophages. This complex targets the IL‑12B promoter to downregulate IL‑12p40 expression, dampening the host immune response. Knocking down ZBTB25 disrupts this repression, leading to enhanced IL‑12 production, which in turn promotes autophagy and contributes to the intracellular killing of M. tuberculosis—highlighting ZBTB25 as a promising target for host‐directed therapeutic strategies against tuberculosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, ZBTB25 has been implicated in the regulation of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection by acting as an E3 ubiquitin ligase. It binds to the viral main protease (Mpro) and facilitates its ubiquitin‑proteasome-dependent degradation, specifically ubiquitinating Mpro at Lys‑100. This regulation shortens the half-life of Mpro, and the genetic ablation of ZBTB25 in host cells leads to enhanced viral infectivity, underscoring its role in antiviral defense and its potential as a novel anticoronaviral target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yair Benita, Zhifang Cao, Cosmas Giallourakis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene enrichment profiles reveal T-cell development, differentiation, and lineage-specific transcription factors including ZBTB25 as a novel NF-AT repressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-01-263855"}], "href": "https://doi.org/10.1182/blood-2010-01-263855"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20410506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20410506"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shu-Chuan Chen, King-Song Jeng, Michael M C Lai "}, {"type": "b", "children": [{"type": "t", "text": "Zinc Finger-Containing Cellular Transcription Corepressor ZBTB25 Promotes Influenza Virus RNA Transcription and Is a Target for Zinc Ejector Drugs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00842-17"}], "href": "https://doi.org/10.1128/JVI.00842-17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28768860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28768860"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aravind Madhavan, K B Arun, Akhil Raj Pushparajan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription Repressor Protein ZBTB25 Associates with HDAC1-Sin3a Complex in Mycobacterium tuberculosis-Infected Macrophages, and Its Inhibition Clears Pathogen by Autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mSphere (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mSphere.00036-21"}], "href": "https://doi.org/10.1128/mSphere.00036-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33627504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33627504"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Travis B Lear, Áine N Boudreau, Karina C Lockwood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.105388"}], "href": "https://doi.org/10.1016/j.jbc.2023.105388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37890782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37890782"}]}]}]}
Synonyms	KUP, C14ORF51, ZNF46
Proteins	ZBT25_HUMAN
NCBI Gene ID	7597
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZBTB25 has 5,500 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 104 datasets.

Click the + buttons to view associations for ZBTB25 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZBTB25 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 ZBTB25 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ZBTB25 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZBTB25 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 ZBTB25 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 ZBTB25 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing ZBTB25 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 ZBTB25 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZBTB25 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZBTB25 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZBTB25 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZBTB25 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 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 ZBTB25 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ZBTB25 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 ZBTB25 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 ZBTB25 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZBTB25 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 ZBTB25 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 ZBTB25 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ZBTB25 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.