ZXDC Gene

HGNC Family	Zinc fingers
Name	ZXD family zinc finger C
Description	Enables C2H2 zinc finger domain binding activity; LRR domain binding activity; and transcription coactivator activity. Involved in positive regulation of DNA-templated transcription. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZXDC is a multifunctional transcription factor that plays a key role in the regulation of major histocompatibility complex (MHC) gene transcription. Early studies revealed that ZXDC interacts directly with the class II trans-activator (CIITA), the master regulator of MHC class II (and, to a lesser degree, MHC class I) gene expression, thereby greatly enhancing promoter activation. Furthermore, ZXDC cooperates with the closely related ZXDA protein to form a complex that is essential for robust MHC II transcription. Distinct transcript isoforms also exist, with one truncated product (ZXDC2) acting as a repressor of MHC II expression, indicating that the ZXDC gene produces both activating and inhibitory signals in immune gene regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional layers of regulation involve post-translational modification of the ZXDC protein. Sumoylation at a specific lysine within its transcriptional activation domain is required for achieving full activity without disrupting ZXDC’s interaction with other co-regulators. This modification fine-tunes its capability to stimulate MHC gene promoters, underscoring the importance of protein modifications in transcriptional control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in MHC gene regulation, ZXDC has been implicated in broader immune and cellular functions. Its larger isoform, ZXDC1, is enriched in myeloid lineages where it induces monocyte differentiation and activates clusters of inflammatory genes—for example, by relieving BCL6-mediated repression at the CCL2 promoter. Furthermore, genetic variants that influence ZXDC expression correlate with altered interferon-γ responses in mycobacterial infections, suggesting a role in anti-tuberculosis immunity. In a distinct pathway, a circular RNA derived from the ZXDC gene (circZXDC) acts as a sponge for miR-125a-3p, leading to enhanced ABCC6 expression that triggers endoplasmic reticulum stress and drives vascular smooth muscle cell transdifferentiation in Moyamoya disease. These multifaceted roles highlight ZXDC as an important regulatory nexus in both immune responses and vascular remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wafa Al-Kandari, Srikarthika Jambunathan, Vandana Navalgund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2006.02.029"}], "href": "https://doi.org/10.1016/j.molimm.2006.02.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16600381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16600381"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wafa Al-Kandari, Rupa Koneni, Vandana Navalgund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2007.04.033"}], "href": "https://doi.org/10.1016/j.jmb.2007.04.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17493635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17493635"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anastasiia Aleksandrova, Oleksandr Galkin, Rupa Koneni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An N- and C-terminal truncated isoform of zinc finger X-linked duplicated C protein represses MHC class II transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-009-0280-5"}], "href": "https://doi.org/10.1007/s11010-009-0280-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19777325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19777325"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Srikarthika Jambunathan, Joseph D Fontes "}, {"type": "b", "children": [{"type": "t", "text": "Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/BC.2007.106"}], "href": "https://doi.org/10.1515/BC.2007.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17696781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17696781"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jon E Ramsey, Joseph D Fontes "}, {"type": "b", "children": [{"type": "t", "text": "The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2013.07.001"}], "href": "https://doi.org/10.1016/j.molimm.2013.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23954399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23954399"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fabienne Jabot-Hanin, Aurélie Cobat, Jacqueline Feinberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An eQTL variant of ZXDC is associated with IFN-γ production following Mycobacterium tuberculosis antigen-specific stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-13017-8"}], "href": "https://doi.org/10.1038/s41598-017-13017-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28993696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28993696"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuan Liu, Yimin Huang, Xincheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells11233792"}], "href": "https://doi.org/10.3390/cells11233792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36497052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36497052"}]}]}]}
Synonyms	ZXDL
Proteins	ZXDC_HUMAN
NCBI Gene ID	79364
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZXDC has 5,512 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 ZXDC from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZXDC 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 ZXDC gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ZXDC protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ZXDC 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 ZXDC gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZXDC 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 ZXDC 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 ZXDC gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ZXDC gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZXDC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ZXDC 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 ZXDC 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 ZXDC 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 ZXDC gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZXDC gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZXDC gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZXDC gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC 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 ZXDC gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZXDC 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 ZXDC from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ZXDC gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ZXDC gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ZXDC gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.