ZIC1 Gene

HGNC Family	Zinc fingers
Name	Zic family member 1
Description	This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development. Aberrant expression of this gene is seen in medulloblastoma, a childhood brain tumor. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 4, a related family member on chromosome 3. This gene encodes a transcription factor that can bind and transactivate the apolipoprotein E gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZIC1 is a zinc‐finger transcription factor with a pivotal role in neural development and cranial morphogenesis. Studies have demonstrated that altered dosage or genetic lesions in ZIC1—often linked with mutations or deletions involving its paralog ZIC4—are implicated in cerebellar malformations such as Dandy–Walker malformation and craniosynostosis. Experimental and clinical evidence from diverse studies shows that aberrant ZIC1 function leads to cerebellar hypoplasia, disrupted cranial suture formation, and other midline defects, although detailed mutational analyses in neural tube defects have largely excluded it as a major risk factor. These findings underscore the importance of ZIC1 in regulating the proliferation, differentiation, and regional patterning of neural progenitors during early brain development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n \nIn addition to transcriptional control during development, ZIC1 is subject to stringent post‐transcriptional regulation. A highly conserved RNA G-quadruplex structure located in the 5′-untranslated region of its mRNA has been shown to inhibit translation in eukaryotic cells without affecting mRNA abundance, suggesting a mechanism by which ZIC1 protein levels can be fine-tuned at the level of translation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n\nIn several cancers, ZIC1 exhibits context-dependent roles that underscore its importance in tumorigenesis. In gastrointestinal malignancies such as colorectal, gastric, and endometrial cancers—as well as in ovarian tumors, mesotheliomas, and gliomas—ZIC1 is frequently downregulated via promoter hypermethylation, thereby acting as a tumor suppressor to restrain cell proliferation, promote apoptosis, and modulate signaling pathways including MAPK, PI3K/Akt, and Wnt/β-catenin. Conversely, in certain mesenchymal tumors like liposarcomas, ZIC1 overexpression appears to promote oncogenic behavior. Collectively, these studies reveal that the epigenetic status and expression levels of ZIC1 have prognostic significance and contribute to disease progression across a spectrum of tumor types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "26"}]}, {"type": "t", "text": "\n\nFurthermore, emerging evidence indicates that ZIC1 contributes to the determination of mesenchymal cell fate. It positively influences osteogenic differentiation while concurrently inhibiting adipogenic commitment, a duality that is modulated by mechanical loading and epigenetic changes—mechanisms that are critical for bone density regulation and skeletal homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Inessa Grinberg, Hope Northrup, Holly Ardinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1420"}], "href": "https://doi.org/10.1038/ng1420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15338008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15338008"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claudia Bagutti, Gaby Forro, Jacqueline Ferralli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.00603"}], "href": "https://doi.org/10.1242/jcs.00603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12783990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12783990"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stephen R F Twigg, Jennifer Forecki, Jacqueline A C Goos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2015.07.007"}], "href": "https://doi.org/10.1016/j.ajhg.2015.07.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26340333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26340333"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jun Aruga, Kathleen J Millen "}, {"type": "b", "children": [{"type": "t", "text": "ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-981-10-7311-3_13"}], "href": "https://doi.org/10.1007/978-981-10-7311-3_13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29442326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29442326"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Riko Klootwijk, Pascal Groenen, Mascha Schijvenaars, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.20402"}], "href": "https://doi.org/10.1002/ajmg.a.20402"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14679585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14679585"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jun Tohyama, Mitsuhiro Kato, Sari Kawasaki, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0016916"}], "href": "https://doi.org/10.1371/journal.pone.0016916"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21347233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21347233"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Liang Jing Wang, Hong Chuan Jin, Xian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZIC1 is downregulated through promoter hypermethylation in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.12.180"}], "href": "https://doi.org/10.1016/j.bbrc.2008.12.180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19135984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19135984"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Wei Qiang, Yuan Zhao, Qi Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ZIC1 gene expression is controlled by DNA and histone methylation in mesenchymal proliferations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.09.061"}], "href": "https://doi.org/10.1016/j.febslet.2007.09.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17936758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17936758"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Li-hong Gan, Jie Pan, Shu-jie Chen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathological significance of increased ZIC1 expression in human endometrial cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Huazhong Univ Sci Technolog Med Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11596-015-1525-z"}], "href": "https://doi.org/10.1007/s11596-015-1525-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26670443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26670443"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yu-Wei Zhang, Jun Ma, Chun-Tao Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roles and correlation of FOXA1 and ZIC1 in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Probl Cancer (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.currproblcancer.2020.100559"}], "href": "https://doi.org/10.1016/j.currproblcancer.2020.100559"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32115254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32115254"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Harish K Datta, Marianne K Kringen, Stephen P Tuck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanical-Stress-Related Epigenetic Regulation of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ZIC1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Transcription Factor in the Etiology of Postmenopausal Osteoporosis."}]}, {"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/ijms23062957"}], "href": "https://doi.org/10.3390/ijms23062957"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35328378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35328378"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Neelima Thottappillil, Mario A Gomez-Salazar, Mingxin Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZIC1 Dictates Osteogenesis Versus Adipogenesis in Human Mesenchymal Progenitor Cells Via a Hedgehog Dependent Mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/stmcls/sxad047"}], "href": "https://doi.org/10.1093/stmcls/sxad047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37317792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37317792"}]}]}]}
Synonyms	CRS6, ZNF201, ZIC
Proteins	ZIC1_HUMAN
NCBI Gene ID	7545
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ZIC1 has 7,839 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 108 datasets.

Click the + buttons to view associations for ZIC1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ZIC1 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 ZIC1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ZIC1 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 ZIC1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ZIC1 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 ZIC1 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 ZIC1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ZIC1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ZIC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ZIC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ZIC1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ZIC1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ZIC1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ZIC1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ZIC1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ZIC1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ZIC1 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 ZIC1 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 ZIC1 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 ZIC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ZIC1 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 ZIC1 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 ZIC1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ZIC1 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 ZIC1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ZIC1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.