ZNF281 Gene

HGNC Family	Zinc fingers
Name	zinc finger protein 281
Description	Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of gene expression; negative regulation of transcription by RNA polymerase II; and positive regulation of DNA-templated transcription. Located in nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF281 functions as a critical transcriptional regulator in cancer progression by driving epithelial-to-mesenchymal transition (EMT) and metastasis. In colorectal cancer, it is embedded in a feed‐forward loop regulated by SNAIL, miR‑34, and p53, ultimately promoting increased migration, invasion, stemness, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In non‑small‑cell lung cancer, upregulation of ZNF281 via the circAGFG1/miR‑203 axis enhances cell proliferation, invasion, migration, and EMT, whereas in hepatocellular carcinoma, elevated levels of ZNF281 correlate with enhanced invasion and poor patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Likewise, in cervical carcinoma, ZNF281 interacts with regulatory partners such as KLF15 to promote disease progression, and in breast cancer, its upregulation in cancer-associated fibroblasts fosters a premetastatic niche via transcriptional activation of inflammatory chemokines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in metastasis, ZNF281 modulates cellular differentiation. In neuroblastoma, elevated ZNF281 antagonizes neuronal differentiation by directly repressing differentiation-promoting genes, whereas its downregulation is associated with the acquisition of a more differentiated phenotype in soft tissue sarcomas and muscle cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nZNF281 also contributes to the maintenance of genomic integrity by orchestrating the cellular response to genotoxic stress. It is rapidly induced following DNA damage and facilitates efficient DNA repair by transcriptionally activating key repair genes—XRCC2 and XRCC4—and by engaging in the early recruitment of the non-homologous end joining factor XRCC4 to damaged chromatin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, ZNF281 is implicated in the pathogenesis of inflammatory and fibrotic disorders of the intestine. It is upregulated in response to inflammatory stimuli in colorectal cells and in mouse models of colitis, where it modulates the expression of inflammatory cytokines and EMT/fibrotic genes, thereby promoting fibroblast activation and extracellular matrix remodeling that contribute to intestinal inflammation and fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefanie Hahn, Rene Jackstadt, Helge Siemens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNAIL and miR-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2013.236"}], "href": "https://doi.org/10.1038/emboj.2013.236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24185900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24185900"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yi-Bo Xue, Meng-Qi Ding, Lei Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircAGFG1 sponges miR-203 to promote EMT and metastasis of non-small-cell lung cancer by upregulating ZNF281 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thorac Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1759-7714.13131"}], "href": "https://doi.org/10.1111/1759-7714.13131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31243884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31243884"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhibo Zhang, Lanfang Yang, Xiaongqing Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA-ZNF281 Interacts with miR-539 to Promote Hepatocellular Carcinoma Cell Invasion and Migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biother Radiopharm (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/cbr.2019.3008"}], "href": "https://doi.org/10.1089/cbr.2019.3008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32073896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32073896"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Y-M Hou, X-P Wang, C-C Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cervical carcinoma progression is aggravated by lncRNA ZNF281 by binding KLF15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202109_26780"}], "href": "https://doi.org/10.26355/eurrev_202109_26780"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34604953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34604953"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huan Zeng, Yixuan Hou, Xinyue Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.74753"}], "href": "https://doi.org/10.7150/thno.74753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36438499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36438499"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marco Pieraccioli, Sara Nicolai, Consuelo Pitolli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1801435115"}], "href": "https://doi.org/10.1073/pnas.1801435115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29941555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29941555"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sara Nicolai, Marco Pieraccioli, Artem Smirnov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF281/Zfp281 is a target of miR-1 and counteracts muscle differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12605"}], "href": "https://doi.org/10.1002/1878-0261.12605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31782884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31782884"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "M Pieraccioli, S Nicolai, A Antonov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF281 contributes to the DNA damage response by controlling the expression of XRCC2 and XRCC4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.320"}], "href": "https://doi.org/10.1038/onc.2015.320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26300006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26300006"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sara Nicolai, Robert Mahen, Giuseppe Raschellà, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-1028-7"}], "href": "https://doi.org/10.1038/s41388-019-1028-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31570788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31570788"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Maria Pierdomenico, Franscesca Palone, Vincenzo Cesi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.02907"}], "href": "https://doi.org/10.3389/fimmu.2018.02907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30619271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30619271"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ilaria Laudadio, Alex Bastianelli, Valerio Fulci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF281 Promotes Colon Fibroblast Activation in TGFβ1-Induced Gut Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms231810261"}], "href": "https://doi.org/10.3390/ijms231810261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36142169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36142169"}]}]}]}
Synonyms	ZNP-99, ZBP-99
Proteins	ZN281_HUMAN
NCBI Gene ID	23528
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZNF281 has 6,380 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 120 datasets.

Click the + buttons to view associations for ZNF281 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ZNF281 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZNF281 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 ZNF281 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ZNF281 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ZNF281 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 ZNF281 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZNF281 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 ZNF281 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ZNF281 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZNF281 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ZNF281 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ZNF281 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 ZNF281 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 ZNF281 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing ZNF281 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZNF281 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZNF281 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZNF281 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZNF281 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 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 ZNF281 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ZNF281 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 ZNF281 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 ZNF281 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZNF281 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 ZNF281 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ZNF281 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.