Details for: ZNF222

Gene ID: 7673

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: ZNF222

Ensembl ID: ENSG00000159885

Description: zinc finger protein 222

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 4
    rCSI 4.85%
    PRS 95.03
  • basal cell of epidermis CL0002187
    CSI 2.74
    rCSI 4.85%
    PRS 93.25
  • suprabasal keratinocyte CL4033013
    CSI 1.39
    rCSI 2.27%
    PRS 94.87

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [ZNF222](/details-gene/7673) is a protein-coding gene located on chromosome 19 that encodes Zinc finger protein 222, a member of the large family of zinc-finger transcription factors. Functional annotations indicate its primary role is in the [nucleus](/details-go/GO:0005634), where it acts as a DNA-binding transcription factor to regulate gene expression ([GO:0006355](/details-go/GO:0006355)). Expression data highlights its significance in distinct and unrelated cell lineages; it is a top marker in a subset of memory T cells, specifically [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), and is also highly significant in epidermal cells, including [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013). This suggests a specialized role in regulating transcriptional programs in both the adaptive immune system and skin tissue. ## Cellular Roles and Expression Landscape The expression profile of [ZNF222](/details-gene/7673) indicates a highly specific, yet functionally diverse, role across different cellular contexts. **Overall**, its most significant expression is observed in the immune system, where it is a prominent marker for [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 4.00). This high significance suggests a potential role in establishing or maintaining the transcriptional identity and long-term persistence of this memory T cell subset. Concurrently, [ZNF222](/details-gene/7673) shows significant expression within the epidermis. It is a marker for both the progenitor [basal cell of epidermis](/details-cell/CL0002187) (CSI: 2.74) and the more differentiated [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 1.39). This pattern suggests that [ZNF222](/details-gene/7673) may be involved in regulating the complex process of keratinocyte differentiation and the maintenance of skin barrier integrity. The dual-lineage significance in both adaptive immunity and epithelial biology points towards a context-dependent regulatory function. ## Pathways and Molecular Function The molecular function of [ZNF222](/details-gene/7673) is consistent with its role as a transcriptional regulator. Gene Ontology annotations confirm its involvement in [dna binding](/details-go/GO:0003677) and its specific activity as a [dna-binding transcription factor](/details-go/GO:0003700). Its function is also linked to [metal ion binding](/details-go/GO:0046872), characteristic of zinc finger proteins that require zinc ions for structural integrity and DNA interaction. Reactome pathway analysis places [ZNF222](/details-gene/7673) within the core machinery of [gene expression (transcription)](https://reactome.org/content/detail/R-HSA-74160), specifically contributing to the [generic transcription pathway](https://reactome.org/content/detail/R-HSA-212436) and [rna polymerase ii transcription](https://reactome.org/content/detail/R-HSA-73857). This fundamental role in transcription is consistent with its high significance in diverse cell types like T cells and keratinocytes, where it likely directs distinct, cell-specific gene expression programs that define their unique functions. ## Research Directions The specific expression of [ZNF222](/details-gene/7673) in both memory T cells and epidermal cells presents intriguing avenues for future research into its distinct regulatory roles in immunity and skin biology. **Proposed Hypotheses:** 1. [ZNF222](/details-gene/7673) is a master regulator required for the maintenance of the memory phenotype in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), possibly by repressing genes associated with terminal differentiation or apoptosis. 2. In the epidermis, [ZNF222](/details-gene/7673) functions as a key transcriptional switch that controls the transition from proliferative [basal cell of epidermis](/details-cell/CL0002187) to differentiated [suprabasal keratinocyte](/details-cell/CL4033013), thereby regulating skin stratification. **Experimental Approach:** To test the role of [ZNF222](/details-gene/7673) in keratinocyte differentiation (Hypothesis 2), a robust approach would involve using CRISPR-Cas9 to knock out the gene in primary human keratinocytes grown in an organotypic 3D skin culture model. The impact of the knockout could be assessed by comparing the resulting epithelial structure to wild-type controls using histology (H&E staining). Further analysis with immunofluorescence for differentiation markers (e.g., Keratin 10, Loricrin, Filaggrin) and proliferation markers (e.g., Ki-67), combined with bulk or single-cell RNA-sequencing, would reveal the specific downstream gene networks regulated by [ZNF222](/details-gene/7673) during epidermal stratification. **Therapeutic Potential:** As an intracellular transcription factor, [ZNF222](/details-gene/7673) represents a challenging therapeutic target for conventional small-molecule inhibitors. However, if its dysregulation is linked to diseases such as cutaneous T-cell lymphoma or skin cancers like squamous cell carcinoma, it could be a candidate for novel therapeutic modalities. Targeted degradation (e.g., using PROTACs) or gene-specific modulation via antisense oligonucleotides or siRNA could offer future strategies for therapeutic intervention, aiming to restore normal transcriptional programs in diseased cells.

Genular Protein ID: 2851989163

Symbol: ZN222_HUMAN

Name: Zinc finger protein 222

UniProtKB Accession Codes:

Q9UK12 G5E9B9 Q8N6G7 Q9P1U5

Database IDs:

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

Citations:

PubMed ID: 12743021

Title: Differential expansion of zinc-finger transcription factor loci in homologous human and mouse gene clusters.

PubMed ID: 12743021

DOI: 10.1101/gr.963903

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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

Sequence Information:

  • Length: 451
  • Mass: 52484
  • Checksum: A54C0DC566138098
  • Sequence:
    • MAKLYEAVTF KDVAVIFTEE ELGLLDPAQR KLYRDVMLEN FRNLLSVGGK IQTEMETVPE 
AGTHEEFSCK QIWEQIASDL TRSQDTTISN SQLFEQDDNP SQIKARLSTV HTREKPFQGE 
NCKQFFSDVS FFDLPQQLYS GEKSHTCDEC GKSFCYISAL HIHQRVHMGV KCYKCDVCGK 
EFSQSSRLQT HQRVHTGEKP FKCEQCGKGF RCRSALKVHC KLHMREKPYN CEKCGKAFMH 
NFQLQKHHRI HTGEKPFKCE ICGKSFCLRS SLNRHCMVHT AEKLYKSEKY GRGFIDRLDL 
HKHQMIHMGQ KPYNCKECGK SFKWSSYLLV HQRVHTGEKP YKCEECGKGY ISKSGLDFHH 
RTHTGERSYN CDNCGKSFRH ASSILNHKKL HCQRKPLKCE DCGKRLVCRS YCKDQQRDHS 
GENPSKCEDC GKRYKRRLNL DIILSLFLND I