ZHX1 Gene

HGNC Family	Homeoboxes, Zinc fingers
Name	zinc fingers and homeoboxes 1
Description	The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 1 of this gene family. In addition to forming homodimers, this protein heterodimerizes with members 2 and 3 of the zinc fingers and homeoboxes family. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 8 open reading frame 76 (C8orf76) gene. [provided by RefSeq, Feb 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZHX1 is a zinc‐finger and homeobox‐containing transcription factor that functions primarily as a transcriptional repressor. Detailed domain mapping has revealed that it harbors several conserved homeodomains and zinc‐finger motifs that facilitate its nuclear localization and enable dimerization as well as binding to other transcriptional regulators such as NF‐YA. In addition, high‐resolution structural studies, including solution NMR analyses, have elucidated the canonical ββ–α folds within its zinc–finger regions and highlighted the contributions of its C–terminal extensions to overall domain architecture."}, {"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": "\nBeyond its intrinsic DNA–binding and repressor functions, ZHX1 exerts regulatory control through interactions with other proteins and epigenetic modifiers. For example, ZHX1 has been shown to interact with DNMT3B, intensifying transcriptional repression when DNMT3B is targeted to specific genes. Moreover, post–translational modifications such as SUMOylation by the conjugating enzyme Ubc9 at defined lysine residues modulate ZHX1’s stability, ubiquitination, and overall transcriptional activity, adding an extra layer of regulatory finesse."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diverse pathological settings, the functional output of ZHX1 appears to be highly context–dependent. In hepatocellular carcinoma and clear cell renal carcinoma, reduced ZHX1 expression has been linked to enhanced cellular proliferation and poorer patient outcomes, suggesting a tumor–suppressive role. Conversely, in cholangiocarcinoma and glioblastoma, elevated levels of ZHX1 correlate with increased proliferation, migration, and invasion, potentially via upregulation of oncogenic mediators such as EGR1, TWIST1, and SNAI2. Additionally, in gastric cancer, microRNA–mediated targeting of ZHX1 promotes tumor progression; while in glomerular diseases, deregulation within the ZHX protein family, including ZHX1, contributes to altered podocyte gene expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazuya Yamada, Hiroko Kawata, Kaoru Matsuura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis and the molecular dissection of zinc-fingers and homeoboxes 1 (ZHX1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)02203-9"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "02203-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12237128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12237128"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kazuya Yamada, Hiroko Kawata, Zhangfei Shou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of zinc-fingers and homeoboxes (ZHX)-1-interacting proteins: molecular cloning and characterization of a member of the ZHX family, ZHX3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021866"}], "href": "https://doi.org/10.1042/BJ20021866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12659632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12659632"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hans Wienk, Ivonne Lammers, Anna Hotze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tandem zinc-finger region of human ZHX adopts a novel C2H2 zinc finger structure with a C-terminal extension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi9001997"}], "href": "https://doi.org/10.1021/bi9001997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19348505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19348505"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xianzhong Xu, Surya V S R K Pulavarti, Alexander Eletsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Struct Funct Genomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10969-014-9184-z"}], "href": "https://doi.org/10.1007/s10969-014-9184-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24941917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24941917"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sung-Hak Kim, Jinah Park, Moon-Chang Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.01.187"}], "href": "https://doi.org/10.1016/j.bbrc.2007.01.187"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17303076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17303076"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shuliang Chen, Xiao Yu, Quan Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SUMOylation of zinc-fingers and homeoboxes 1 (ZHX1) by Ubc9 regulates its stability and transcriptional repression activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.24579"}], "href": "https://doi.org/10.1002/jcb.24579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23686912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23686912"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gang Liu, Lionel C Clement, Yashpal S Kanwar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZHX proteins regulate podocyte gene expression during the development of nephrotic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M606664200"}], "href": "https://doi.org/10.1074/jbc.M606664200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17056598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17056598"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jianping Wang, Dejie Liu, Xiaohong Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Construction of a recombinant eukaryotic human ZHX1 gene expression plasmid and the role of ZHX1 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2013.1700"}], "href": "https://doi.org/10.3892/mmr.2013.1700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24064680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24064680"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zhenqiang Wang, Xingjie Ma, Qiang Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-199a-3p promotes gastric cancer progression by targeting ZHX1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2014.09.047"}], "href": "https://doi.org/10.1016/j.febslet.2014.09.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25448600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25448600"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ryuk-Jun Kwon, Myoung-Eun Han, Ji-Young Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0165516"}], "href": "https://doi.org/10.1371/journal.pone.0165516"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27835650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27835650"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ryuk-Jun Kwon, Yun Hak Kim, Dae Cheon Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0171036"}], "href": "https://doi.org/10.1371/journal.pone.0171036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28152006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28152006"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ryuk-Jun Kwon, Myoung-Eun Han, Youn-Jae Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1010428317694575"}], "href": "https://doi.org/10.1177/1010428317694575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28351300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28351300"}]}]}]}
Proteins	ZHX1_HUMAN
NCBI Gene ID	11244
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZHX1 has 5,425 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 109 datasets.

Click the + buttons to view associations for ZHX1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ZHX1 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 ZHX1 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 ZHX1 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 ZHX1 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 ZHX1 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 ZHX1 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 ZHX1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ZHX1 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 ZHX1 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 ZHX1 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 ZHX1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ZHX1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ZHX1 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 ZHX1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZHX1 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 ZHX1 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 ZHX1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZHX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ZHX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ZHX1 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 ZHX1 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 ZHX1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZHX1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZHX1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZHX1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ZHX1 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 ZHX1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ZHX1 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 ZHX1 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 ZHX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ZHX1 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 ZHX1 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 ZHX1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZHX1 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 ZHX1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ZHX1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ZHX1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ZHX1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of ZHX1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of ZHX1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ZHX1 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.