ZFR Gene

Name	zinc finger RNA binding protein
Description	This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells. [provided by RefSeq, Sep 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that circular RNA isoforms of ZFR (circZFR) perform oncogenic functions in multiple cancers. In papillary thyroid carcinoma, circZFR is significantly upregulated and promotes cell proliferation, migration, and invasion by acting as a competing endogenous RNA that modulates the miR‐1261/C8orf4 axis. Similarly, in hepatocellular carcinoma, increased expression of circZFR has been associated with tumor development. In non‐small cell lung cancer, decreased miR-141-3p levels result in derepression of ZFR, thereby enhancing cell proliferation, while emerging observations in cervical cancer and other malignancies underscore the broader importance of circRNAs in tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its non‐coding roles, the protein product of ZFR has been identified in forward genetic screens as a potent oncogene in colorectal and liver cancers. Overexpression of ZFR accelerates cell proliferation and tumor progression by transcriptionally repressing targets such as the tumor-suppressor candidate FAM49B. This finding highlights the functional significance of ZFR in digestive system malignancies and points to its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, ZFR functions as a key RNA-binding protein that governs post-transcriptional RNA processing and innate immune responses. In macrophages, ZFR controls alternative pre-mRNA splicing to prevent aberrant splicing and the ensuing nonsense-mediated decay of transcripts like the histone variant macroH2A1, thereby tempering interferon responses. Moreover, ZFR is subject to regulation via alternative polyadenylation that modulates its negative feedback by an intronic miRNA (miR-579), and in retinal endothelial cells high glucose conditions induce ZFR upregulation to promote angiogenesis in diabetic retinopathy. Collectively, these observations reveal the multifaceted nature of ZFR in both cellular homeostasis and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hong Wei, Lin Pan, Deyou Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.05.174"}], "href": "https://doi.org/10.1016/j.bbrc.2018.05.174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29842886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29842886"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weisong Li, Yongmei Cui, Dan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-141-3p functions as a tumor suppressor through directly targeting ZFR in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.12.089"}], "href": "https://doi.org/10.1016/j.bbrc.2018.12.089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30611568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30611568"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui Xu, Shiwu Yin, Meng Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA circZFR Promotes Hepatocellular Carcinoma Progression by Regulating miR-375/HMGA2 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Dis Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10620-020-06805-2"}], "href": "https://doi.org/10.1007/s10620-020-06805-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33433801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33433801"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mingyi Zhou, Zhuo Yang, Danbo Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-021-01849-2"}], "href": "https://doi.org/10.1186/s13046-021-01849-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33516252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33516252"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Li Zhang, Sai He, Hao Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatobiliary Pancreat Dis Int (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hbpd.2023.07.003"}], "href": "https://doi.org/10.1016/j.hbpd.2023.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37516591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37516591"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yanrong Long, Teresa A Marian, Zhubo Wei "}, {"type": "b", "children": [{"type": "t", "text": "ZFR promotes cell proliferation and tumor development in colorectal and liver cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.04.103"}], "href": "https://doi.org/10.1016/j.bbrc.2019.04.103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31010678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31010678"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ludwig Christian Hinske, Pedro A F Galante, Elisabeth Limbeck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative polyadenylation allows differential negative feedback of human miRNA miR-579 on its host gene ZFR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0121507"}], "href": "https://doi.org/10.1371/journal.pone.0121507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25799583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25799583"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nazmul Haque, Ryota Ouda, Chao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZFR coordinates crosstalk between RNA decay and transcription in innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03326-5"}], "href": "https://doi.org/10.1038/s41467-018-03326-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29559679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29559679"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xindan Xing, Hanying Wang, Yuan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "O- glycosylation can regulate the proliferation and migration of human retinal microvascular endothelial cells through ZFR in high glucose condition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.03.135"}], "href": "https://doi.org/10.1016/j.bbrc.2019.03.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30914198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30914198"}]}]}]}
Synonyms	SPG71, ZFR1
Proteins	ZFR_HUMAN
NCBI Gene ID	51663
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZFR has 8,583 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 118 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR 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 ZFR gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZFR 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 ZFR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ZFR protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ZFR 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 ZFR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZFR 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 ZFR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ZFR gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ZFR gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing ZFR 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 ZFR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZFR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ZFR 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 ZFR 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 ZFR 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 ZFR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZFR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZFR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZFR gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ZFR 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 ZFR 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 ZFR 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 ZFR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ZFR 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 ZFR 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 ZFR gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZFR 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 ZFR 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 ZFR gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.