Details for: ZIC1

Gene ID: 7545

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ZIC1

Ensembl ID: ENSG00000152977

Description: Zic family member 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • Bergmann glial cell CL0000644
    CSI 27.31
    rCSI 37.36%
    PRS 92.22
  • cerebellar granule cell CL0001031
    CSI 23.68
    rCSI 34.82%
    PRS 93.28
  • interneuron CL0000099
    CSI 11.7
    rCSI 23.49%
    PRS 93.7
  • radial glial cell CL0000681
    CSI 9.07
    rCSI 12.6%
    PRS 95.85
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 8.73
    rCSI 11.21%
    PRS 94.32
  • macroglial cell CL0000126
    CSI 8.58
    rCSI 22.06%
    PRS 93.86
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 8.23
    rCSI 9.5%
    PRS 91.9
  • vascular leptomeningeal cell CL4023051
    CSI 8.19
    rCSI 14.37%
    PRS 94.73
  • choroid plexus epithelial cell CL0000706
    CSI 7.35
    rCSI 12.03%
    PRS 92.91
  • glioblast CL0000030
    CSI 7.05
    rCSI 11.24%
    PRS 92.02
  • glial cell CL0000125
    CSI 6.7
    rCSI 25.51%
    PRS 92.58
  • melanocyte of skin CL1000458
    CSI 6.37
    rCSI 8.69%
    PRS 75.8
  • Mueller cell CL0000636
    CSI 6.24
    rCSI 14.24%
    PRS 93.05
  • ependymal cell CL0000065
    CSI 5.9
    rCSI 11.97%
    PRS 85.13
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 5.7
    rCSI 10.35%
    PRS 92.86
  • brain vascular cell CL4023072
    CSI 3.96
    rCSI 41.02%
    PRS 92.26
  • inhibitory interneuron CL0000498
    CSI 3.94
    rCSI 9.1%
    PRS 91.37
  • basal cell of epidermis CL0002187
    CSI 3.89
    rCSI 6.89%
    PRS 75.12
  • Schwann cell CL0002573
    CSI 3.78
    rCSI 10.75%
    PRS 94.47
  • neural cell CL0002319
    CSI 3.37
    rCSI 12.74%
    PRS 87.5
  • GABAergic neuron CL0000617
    CSI 3.09
    rCSI 10.34%
    PRS 87.99
  • neural progenitor cell CL0011020
    CSI 3.04
    rCSI 13.36%
    PRS 88.98
  • cerebral cortex endothelial cell CL1001602
    CSI 2.98
    rCSI 5.16%
    PRS 93.99
  • suprabasal keratinocyte CL4033013
    CSI 2.46
    rCSI 4.01%
    PRS 76.06
  • endothelial cell of vascular tree CL0002139
    CSI 2.29
    rCSI 12.54%
    PRS 93.66
  • smooth muscle cell CL0000192
    CSI 1.99
    rCSI 4.75%
    PRS 93.55
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.51
    rCSI 1.82%
    PRS 81.79
  • central nervous system neuron CL2000029
    CSI 0.36
    rCSI 2.63%
    PRS 92.01

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ZIC1](/details-gene/7545) is a protein-coding gene located on chromosome 3q24 that encodes the Zic family member 1, a C2H2-type zinc finger transcription factor. Functionally, [ZIC1](/details-gene/7545) is a critical regulator of embryonic development, particularly within the central nervous system. Its involvement is well-documented in processes such as '[brain development](/details-cell/GO0007420)', '[spinal cord development](/details-cell/GO0021510)', and the '[specification of the neural plate border](/details-cell/R-HSA-9834899)'. Expression data highlights its profound significance in specialized neural and glial cell populations, with its highest cell significance index (CSI) observed in [Bergmann glial cell](/details-cell/CL0000644) (CSI: 27.31) and [cerebellar granule cell](/details-cell/CL0001031) (CSI: 23.68). Clinically, mutations in [ZIC1](/details-gene/7545) are associated with significant neurodevelopmental disorders, including craniosynostosis and cortical malformations ([153245](https://omim.org/entry/600470)). ## Cellular Roles and Expression Landscape The expression profile of [ZIC1](/details-gene/7545) underscores its highly specialized role in neurogenesis and glial cell biology. **Overall**, the gene demonstrates exceptional significance in cells of the cerebellum, including [Bergmann glial cell](/details-cell/CL0000644) and [cerebellar granule cell](/details-cell/CL0001031), which is consistent with early research identifying its predominant expression in this brain region ([Link](https://pubmed.ncbi.nlm.nih.gov/8542595/)). Beyond the cerebellum, [ZIC1](/details-gene/7545) is a key marker for various neural progenitor and glial populations. Its high significance in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031), [radial glial cell](/details-cell/CL0000681), and [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) suggests a role in maintaining progenitor states and guiding cell fate decisions during CNS development. The gene's importance extends to mature glial support cells such as [macroglial cell](/details-cell/CL0000126) and specialized types like the [Mueller cell](/details-cell/CL0000636) of the retina. Notably, its significant expression in [glioblast](/details-cell/CL0000030) suggests a potential role in neural-derived cancers through the dysregulation of developmental pathways. The gene also shows relevance in [melanocyte of skin](/details-cell/CL1000458), pointing to a function in neural crest-derived lineages outside the CNS. ## Pathways and Molecular Function Functionally, [ZIC1](/details-gene/7545) operates as a '[dna-binding transcription activator activity, rna polymerase ii-specific](/details-cell/GO0001228)'. Its molecular activities are primarily centered on '[sequence-specific double-stranded dna binding](/details-cell/GO1990837)', enabling it to regulate the expression of target genes essential for development. The biological processes associated with [ZIC1](/details-gene/7545) are tightly aligned with its cellular expression pattern. Its high CSI in neural progenitors and developing neurons is explained by its deep involvement in fundamental neurodevelopmental pathways, including '[central nervous system development](/details-cell/GO0007417)', '[gastrulation](/details-cell/R-HSA-9758941)', and the '[specification of the neural plate border](/details-cell/R-HSA-9834899)'. The gene's role in specific brain regions is highlighted by its association with '[hippocampus development](/details-cell/GO0021766)' and '[olfactory bulb development](/details-cell/GO0021772)'. Furthermore, its connection to the '[Mitf-m-regulated melanocyte development](/details-cell/R-HSA-9730414)' pathway provides a clear molecular basis for its significant expression in [melanocyte of skin](/details-cell/CL1000458). The clinical phenotypes associated with [ZIC1](/details-gene/7545) mutations, such as cortical malformations ([Link](https://doi.org/10.1016/j.ejmg.2018.10.018)), are a direct consequence of its critical function in these developmental processes. ## Research Directions The data strongly indicate that [ZIC1](/details-gene/7545) is a master regulator of neurodevelopment whose dysregulation can lead to severe congenital defects and may be implicated in oncogenesis. Its high significance in [glioblast](/details-cell/CL0000030) and established link to medulloblastoma ([Link](https://pubmed.ncbi.nlm.nih.gov/8542595/)) suggest that aberrant reactivation of this developmental transcription factor is a potential driver of brain tumors. Based on these findings, several testable hypotheses can be proposed: 1. Gain-of-function mutations in [ZIC1](/details-gene/7545), as seen in coronal craniosynostosis ([Link](https://doi.org/10.1016/j.ajhg.2015.07.007)), may lead to premature or altered differentiation of neural crest-derived cranial progenitors by disrupting the normal transcriptional landscape required for skull development. 2. The aberrant re-expression of [ZIC1](/details-gene/7545) in glial precursors is a key event in the formation of specific subtypes of glioblastoma and medulloblastoma, where it drives proliferation and inhibits terminal differentiation, thereby maintaining a tumorigenic progenitor-like state. To test the second hypothesis, a key experiment would involve the use of patient-derived glioblastoma stem cell (GSC) lines that exhibit high endogenous [ZIC1](/details-gene/7545) expression. CRISPR-Cas9-mediated knockout of [ZIC1](/details-gene/7545) would be performed in these GSCs. The resulting knockout cells would be compared to control cells to assess changes in self-renewal capacity using in vitro limiting dilution assays (sphere formation) and proliferation rates. Furthermore, the effect on differentiation could be evaluated by culturing the cells in differentiation-promoting media and measuring the expression of mature glial markers like GFAP and MBP via immunofluorescence and qPCR. Downstream transcriptional changes would be comprehensively profiled using RNA-sequencing to identify the effector pathways through which [ZIC1](/details-gene/7545) promotes tumorigenesis. As a therapeutic target, [ZIC1](/details-gene/7545) presents challenges due to its nature as a nuclear transcription factor, which are notoriously difficult to inhibit directly with small molecules. However, given its highly specific expression profile in certain cancers compared to most healthy adult tissues, it represents a strong candidate for indirect therapeutic strategies. Inhibition of its activity would be the therapeutic goal. This could potentially be achieved by developing molecules that disrupt its interaction with essential protein co-factors or by targeting its key downstream transcriptional targets that are more 'druggable'. Therefore, while not a conventional target, [ZIC1](/details-gene/7545) could serve as a critical biomarker and a focal point for developing novel therapeutic approaches against developmental-pathway-driven brain tumors.

Genular Protein ID: 3137358208

Symbol: ZIC1_HUMAN

Name: Zinc finger protein ZIC 1

UniProtKB Accession Codes:

Q15915 Q2M3N1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 24 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8542595

Title: Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma.

PubMed ID: 8542595

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 26340333

Title: Gain-of-function mutations in ZIC1 are associated with coronal craniosynostosis and learning disability.

PubMed ID: 26340333

DOI: 10.1016/j.ajhg.2015.07.007

PubMed ID: 30391508

Title: Mutated zinc finger protein of the cerebellum 1 leads to microcephaly, cortical malformation, callosal agenesis, cerebellar dysplasia, tethered cord and scoliosis.

PubMed ID: 30391508

DOI: 10.1016/j.ejmg.2018.10.018

Sequence Information:

  • Length: 447
  • Mass: 48309
  • Checksum: 4DA3E32C99BF1AAE
  • Sequence:
    • MLLDAGPQYP AIGVTTFGAS RHHSAGDVAE RDVGLGINPF ADGMGAFKLN PSSHELASAG 
QTAFTSQAPG YAAAAALGHH HHPGHVGSYS SAAFNSTRDF LFRNRGFGDA AAAASAQHSL 
FAASAGGFGG PHGHTDAAGH LLFPGLHEQA AGHASPNVVN GQMRLGFSGD MYPRPEQYGQ 
VTSPRSEHYA APQLHGYGPM NVNMAAHHGA GAFFRYMRQP IKQELICKWI EPEQLANPKK 
SCNKTFSTMH ELVTHVTVEH VGGPEQSNHI CFWEECPREG KPFKAKYKLV NHIRVHTGEK 
PFPCPFPGCG KVFARSENLK IHKRTHTGEK PFKCEFEGCD RRFANSSDRK KHMHVHTSDK 
PYLCKMCDKS YTHPSSLRKH MKVHESSSQG SQPSPAASSG YESSTPPTIV SPSTDNPTTS 
SLSPSSSAVH HTAGHSALSS NFNEWYV