Details for: ZNF219

Gene ID: 51222

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: ZNF219

Ensembl ID: ENSG00000165804

Description: zinc finger protein 219

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Dna binding
    (GO:0003677)
  • G protein-coupled receptor signaling pathway
    (GO:0007186)
  • Histamine receptor activity
    (GO:0004969)
  • Limb bud formation
    (GO:0060174)
  • Membrane
    (GO:0016020)
  • Metal ion binding
    (GO:0046872)
  • Negative regulation of dna-templated transcription
    (GO:0045892)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleoplasm
    (GO:0005654)
  • Nucleus
    (GO:0005634)
  • Positive regulation of chondrocyte differentiation
    (GO:0032332)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Regulation of dna-templated transcription
    (GO:0006355)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)

Significant Cells

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

  • respiratory suprabasal cell CL4033048
    CSI 5.86
    rCSI 7.51%
    PRS 97.76
  • interneuron CL0000099
    CSI 3.77
    rCSI 7.56%
    PRS 94.78
  • rod bipolar cell CL0000751
    CSI 3.22
    rCSI 5.79%
    PRS 94.46
  • progenitor cell CL0011026
    CSI 3.02
    rCSI 6.43%
    PRS 93.43
  • neural crest cell CL0011012
    CSI 3.02
    rCSI 2.38%
    PRS 94.93
  • myoepithelial cell CL0000185
    CSI 2.97
    rCSI 7.52%
    PRS 98.04
  • stem cell CL0000034
    CSI 2.74
    rCSI 2.64%
    PRS 95.91
  • colon epithelial cell CL0011108
    CSI 2.59
    rCSI 2.72%
    PRS 96.13
  • ependymal cell CL0000065
    CSI 2.51
    rCSI 5.1%
    PRS 87.09
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.39
    rCSI 2.76%
    PRS 93.24
  • transit amplifying cell of colon CL0009011
    CSI 2.37
    rCSI 2.78%
    PRS 97.63
  • colonocyte CL1000347
    CSI 2.3
    rCSI 3.29%
    PRS 96.09
  • radial glial cell CL0000681
    CSI 2.15
    rCSI 2.99%
    PRS 96.76
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.09
    rCSI 2.68%
    PRS 95.44
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.06
    rCSI 4.62%
    PRS 91.93
  • peripheral nervous system neuron CL2000032
    CSI 1.95
    rCSI 2.66%
    PRS 94.22
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.88
    rCSI 5.56%
    PRS 96.88
  • vascular associated smooth muscle cell CL0000359
    CSI 1.86
    rCSI 6.03%
    PRS 96.85
  • glioblast CL0000030
    CSI 1.85
    rCSI 2.95%
    PRS 93.36
  • lung pericyte CL0009089
    CSI 1.66
    rCSI 4.37%
    PRS 98.65
  • retinal cone cell CL0000573
    CSI 1.6
    rCSI 2.58%
    PRS 92.79

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)

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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 [ZNF219](/details-gene/51222) (Zinc Finger Protein 219) is a protein-coding gene located on chromosome 14q11.2. It encodes a transcription factor characterized by multiple zinc finger domains, which facilitate its primary function in DNA binding and the regulation of gene expression ([Link](https://doi.org/10.1093/dnares/7.2.137)). As a sequence-specific DNA-binding protein, [ZNF219](/details-gene/51222) functions predominantly within the [nucleus](/details-cell/GO0005634) to both positively and negatively regulate transcription from RNA polymerase II promoters ([Link](https://doi.org/10.1093/dnares/10.4.155)). **Overall** expression data highlight its significance in diverse and specialized cell types, including [respiratory suprabasal cell](/details-cell/CL4033048), various neuronal subtypes like [interneuron](/details-cell/CL0000099), and progenitor populations such as [stem cell](/details-cell/CL0000034). This pattern suggests a fundamental role in establishing and maintaining cellular identity and developmental processes across multiple tissues. ## Cellular Roles and Expression Landscape The expression profile of [ZNF219](/details-gene/51222) indicates a broad but specific role in differentiated tissues and progenitor cell populations. **Overall**, the gene shows the highest significance in epithelial cells of the respiratory tract ([respiratory suprabasal cell](/details-cell/CL4033048)) and colon ([colon epithelial cell](/details-cell/CL0011108), [colonocyte](/details-cell/CL1000347)), suggesting a function in epithelial homeostasis and differentiation. Concurrently, [ZNF219](/details-gene/51222) is a significant factor in the central nervous system. It demonstrates high CSI values in multiple neural cell types, including [interneuron](/details-cell/CL0000099), [rod bipolar cell](/details-cell/CL0000751), [ependymal cell](/details-cell/CL0000065), and glial cells like [radial glial cell](/details-cell/CL0000681) and [astrocyte of the cerebral cortex](/details-cell/CL0002605). Its importance in neural development is further underscored by its expression in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) and [neural crest cell](/details-cell/CL0011012). This widespread neuronal expression is consistent with its known role in regulating the alpha-synuclein promoter, a key gene in neurological function and disease ([Link](https://doi.org/10.1111/j.1471-4159.2009.06250.x)). Furthermore, the high significance of [ZNF219](/details-gene/51222) in undifferentiated cell populations, such as [progenitor cell](/details-cell/CL0011026) and [stem cell](/details-cell/CL0000034), points towards a role in developmental processes and the regulation of pluripotency or lineage commitment. ## Pathways and Molecular Function Functionally, [ZNF219](/details-gene/51222) operates as a transcriptional regulator with dual capabilities. Gene Ontology annotations confirm its involvement in both [negative regulation of dna-templated transcription](/details-cell/GO0045892) and [positive regulation of transcription by rna polymerase ii](/details-cell/GO0045944). Its molecular function is defined by its ability to bind DNA in a sequence-specific manner ([dna-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO0000981)), a role that has been experimentally validated ([Link](https://doi.org/10.1093/dnares/10.4.155)). The gene's involvement in developmental pathways is highlighted by its association with processes such as [limb bud formation](/details-cell/GO0060174) and [positive regulation of chondrocyte differentiation](/details-cell/GO0032332). These functions align with its expression in progenitor and stem cell populations. The established link to the regulation of the alpha-synuclein gene promoter connects [ZNF219](/details-gene/51222) directly to neurobiology and the potential pathology of synucleinopathies ([Link](https://doi.org/10.1111/j.1471-4159.2009.06250.x)). Less characterized but annotated functions include roles in [G protein-coupled receptor signaling pathway](/details-cell/GO0007186) and [histamine receptor activity](/details-cell/GO0004969), suggesting broader roles beyond transcriptional control. ## Research Directions The diverse expression pattern and dual regulatory function of [ZNF219](/details-gene/51222) open several avenues for future investigation. Its high significance in both neuronal and epithelial tissues, coupled with its role as a transcription factor, makes it a candidate for involvement in both neurodegenerative and hyperproliferative diseases. **Testable Hypotheses:** 1. **Role in Synucleinopathy:** Given its established function in regulating the alpha-synuclein promoter and its high expression in [interneuron](/details-cell/CL0000099) and other CNS cells, it is hypothesized that dysregulation or mutation of [ZNF219](/details-gene/51222) alters alpha-synuclein expression levels in specific neuronal subtypes, thereby contributing to the initiation or progression of neurodegenerative diseases like Parkinson's disease. 2. **Regulator of Epithelial Differentiation:** The high CSI of [ZNF219](/details-gene/51222) in [respiratory suprabasal cell](/details-cell/CL4033048) and [transit amplifying cell of colon](/details-cell/CL0009011) suggests a hypothesis where [ZNF219](/details-gene/51222) acts as a critical switch in epithelial cell fate. Its loss-of-function may lead to failed differentiation and barrier dysfunction, while its gain-of-function could contribute to hyperproliferative conditions or carcinogenesis by disrupting the normal balance of cell turnover. **Proposed Experimental Approach:** To test the hypothesis regarding its role in synucleinopathy, a targeted experiment could be conducted using human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons. CRISPR interference (CRISPRi) could be employed to specifically repress [ZNF219](/details-gene/51222) expression in these cultures. The impact on alpha-synuclein (SNCA) mRNA and protein levels would be quantified via RT-qPCR and western blot, respectively. Furthermore, immunofluorescence microscopy could be used to assess changes in alpha-synuclein localization and the formation of protein aggregates, a key pathological hallmark. **Therapeutic Potential:** As a nuclear transcription factor, [ZNF219](/details-gene/51222) presents a challenging target for traditional small molecule inhibitors. Its therapeutic modulation would likely require advanced strategies such as antisense oligonucleotides or gene therapy to alter its expression levels in target cells, particularly within the central nervous system. If its dysregulation contributes to disease (e.g., overexpression leading to neurotoxicity), a strategy of targeted inhibition could be beneficial. Conversely, if its loss promotes pathology, targeted activation or gene replacement might be considered. Its broad expression in multiple essential cell types, however, suggests that systemic modulation could have significant off-target effects, necessitating highly specific delivery systems.

Genular Protein ID: 2671551030

Symbol: ZN219_HUMAN

Name: Zinc finger protein 219

UniProtKB Accession Codes:

Q9P2Y4 D3DS16 Q53Y57 Q8IYC1 Q9BW28

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 8 Ensembl 3 ExpressionAtlas 1 GO 16 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 7 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10819330

Title: Isolation and characterization of a novel zinc finger gene, ZNF219, and mapping to the human chromosome 14q11 region.

PubMed ID: 10819330

DOI: 10.1093/dnares/7.2.137

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: 14621294

Title: Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor.

PubMed ID: 14621294

DOI: 10.1093/dnares/10.4.155

PubMed ID: 19549071

Title: Functional dissection of the alpha-synuclein promoter: transcriptional regulation by ZSCAN21 and ZNF219.

PubMed ID: 19549071

DOI: 10.1111/j.1471-4159.2009.06250.x

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 722
  • Mass: 76877
  • Checksum: AB2B6B37904FC14B
  • Sequence:
    • MEGSRPRAPS GHLAPSPPAF DGELDLQRYS NGPAVSAGSL GMGAVSWSES RAGERRFPCP 
VCGKRFRFNS ILALHLRAHP GAQAFQCPHC GHRAAQRALL RSHLRTHQPE RPRSPAARLL 
LELEERALLR EARLGRARSS GGMQATPATE GLARPQAPSS SAFRCPYCKG KFRTSAERER 
HLHILHRPWK CGLCSFGSSQ EEELLHHSLT AHGAPERPLA ATSAAPPPQP QPQPPPQPEP 
RSVPQPEPEP EPEREATPTP APAAPEEPPA PPEFRCQVCG QSFTQSWFLK GHMRKHKASF 
DHACPVCGRC FKEPWFLKNH MKVHASKLGP LRAPGPASGP ARAPQPPDLG LLAYEPLGPA 
LLLAPAPTPA ERREPPSLLG YLSLRAGEGR PNGEGAEPGP GRSFGGFRPL SSALPARARR 
HRAEEPEEEE EVVEAEEETW ARGRSLGSLA SLHPRPGEGP GHSASAAGAQ ARSTATQEEN 
GLLVGGTRPE GGRGATGKDC PFCGKSFRSA HHLKVHLRVH TGERPYKCPH CDYAGTQSGS 
LKYHLQRHHR EQRSGAGPGP PPEPPPPSQR GSAPQSGAKP SPQPATWVEG ASSPRPPSSG 
AGPGSRRKPA SPGRTLRNGR GGEAEPLDLS LRAGPGGEAG PGGALHRCLF CPFATGAPEL 
MALHLQVHHS RRARGRRPPQ ADASPPYARV PSGETPPSPS QEGEEGSGLS RPGEAGLGGQ 
ER