Details for: ZNF165

Gene ID: 7718

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: ZNF165

Ensembl ID: ENSG00000197279

Description: zinc finger protein 165

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Metal ion binding
    (GO:0046872)
  • Nucleus
    (GO:0005634)
  • Protein binding
    (GO:0005515)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)

Significant Cells

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

  • stem cell CL0000034
    CSI 3.53
    rCSI 3.41%
    PRS 92.87
  • BEST4+ enteroycte CL4030026
    CSI 3.38
    rCSI 4.21%
    PRS 94.47
  • pancreatic A cell CL0000171
    CSI 2.86
    rCSI 3%
    PRS 95.8
  • enteroendocrine cell CL0000164
    CSI 2.25
    rCSI 3.07%
    PRS 93.22
  • placental villous trophoblast CL2000060
    CSI 1.82
    rCSI 2.82%
    PRS 93.71
  • syncytiotrophoblast cell CL0000525
    CSI 1.81
    rCSI 5.22%
    PRS 94.95
  • pancreatic acinar cell CL0002064
    CSI 1.8
    rCSI 2.39%
    PRS 96.54
  • basal cell of epidermis CL0002187
    CSI 1.56
    rCSI 2.76%
    PRS 71.11
  • pancreatic ductal cell CL0002079
    CSI 1.39
    rCSI 2.7%
    PRS 95.75
  • melanocyte of skin CL1000458
    CSI 1.14
    rCSI 1.55%
    PRS 71.17

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 [ZNF165](/details-gene/7718) is a protein-coding gene located on chromosome 6p22.1 that encodes Zinc Finger Protein 165. Based on its structural motifs and functional annotations, [ZNF165](/details-gene/7718) is characterized as a DNA-binding transcription factor that likely regulates gene expression via RNA polymerase II. Expression data from a broad **Overall** context reveals its highest significance in a diverse array of cell types, including [stem cell](/details-cell/CL0000034), specialized secretory cells like [pancreatic A cell](/details-cell/CL0000171), and placental tissues such as [placental villous trophoblast](/details-cell/CL2000060). This pattern suggests a role in maintaining pluripotency, directing terminal differentiation, or executing specialized cellular programs across multiple tissues. Early research characterized the gene as part of the Kruppel gene family, containing a conserved SCAN box domain and showing specific expression in the testis [Link](https://doi.org/10.1006/geno.1995.1178), [Link](https://doi.org/10.1006/geno.1997.4806). ## Cellular Roles and Expression Landscape The expression profile of [ZNF165](/details-gene/7718) highlights its importance in several distinct cellular contexts, suggesting a role as a regulator of specialized cell states rather than a broad homeostatic factor. **Overall**, the gene shows the highest significance in progenitor and undifferentiated cells, evidenced by its top rank in [stem cell](/details-cell/CL0000034) (CSI: 3.53) and high significance in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.56). This is consistent with a potential function in maintaining self-renewal or guiding lineage commitment. Concurrently, [ZNF165](/details-gene/7718) is a significant marker for several highly specialized, terminally differentiated cell types. These include: * **Gastrointestinal and Endocrine Cells:** High significance is observed in [BEST4+ enteroycte](/details-cell/CL4030026) (CSI: 3.38), [pancreatic A cell](/details-cell/CL0000171) (CSI: 2.86), [enteroendocrine cell](/details-cell/CL0000164) (CSI: 2.25), and [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 1.80). This suggests its involvement in orchestrating the transcriptional programs required for specialized digestive or hormonal functions. * **Placental Cells:** The gene is highly significant in both [placental villous trophoblast](/details-cell/CL2000060) (CSI: 1.82) and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 1.81), pointing towards a specific role in placental development and function. * **Other Specialized Cells:** Notable significance is also seen in [melanocyte of skin](/details-cell/CL1000458) (CSI: 1.14), further broadening its role in differentiated cell types. Collectively, this diverse expression landscape suggests that [ZNF165](/details-gene/7718) may be a master regulator activated during specific differentiation pathways to establish and maintain unique cellular identities. ## Pathways and Molecular Function Functional annotations corroborate the role of [ZNF165](/details-gene/7718) as a nuclear transcription factor. The protein is localized to the [nucleus](/details-cell/GO:0005634) and is involved in fundamental regulatory processes. * **Transcriptional Regulation:** The primary annotated function is the [regulation of transcription by rna polymerase ii](/details-cell/GO:0006357). This is achieved through its [dna-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981) and its ability to bind specifically to [rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-cell/GO:0000978). This molecular function is the likely mechanism by which it directs the unique gene expression programs observed in the cell types where it is most active. * **Structural and Binding Domains:** As a zinc finger protein, it possesses [metal ion binding](/details-cell/GO:0046872) capabilities, which are critical for maintaining the structural integrity of its DNA-binding domain. It is also annotated with a general [protein binding](/details-cell/GO:0005515) function, suggesting it may operate as part of a larger transcriptional complex to exert its effects. These functions are consistent with a role in controlling the expression of downstream target genes that define the identity and function of cells ranging from stem cells to terminally differentiated pancreatic and placental cells. ## Research Directions The specific and diverse expression pattern of [ZNF165](/details-gene/7718) in both progenitor and highly specialized cells opens several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in [stem cell](/details-cell/CL0000034) and epidermal progenitor cells, [ZNF165](/details-gene/7718) may act as a critical switch that governs the transition from pluripotency to specific lineage commitment. Its downregulation could be required for differentiation to proceed, while its sustained expression might maintain a progenitor-like state. 2. The strong expression of [ZNF165](/details-gene/7718) across multiple endocrine and exocrine cell types ([pancreatic A cell](/details-cell/CL0000171), [enteroendocrine cell](/details-cell/CL0000164), [pancreatic acinar cell](/details-cell/CL0002064)) suggests it is a master regulator of genes involved in the synthesis, processing, and secretion of hormones and digestive enzymes. **Key Experimental Approach:** To test the hypothesis that [ZNF165](/details-gene/7718) regulates pancreatic endocrine cell fate (Hypothesis 2), one could utilize an *in vitro* model of pancreatic organoid differentiation from human induced pluripotent stem cells (iPSCs). A CRISPR-Cas9-mediated knockout of [ZNF165](/details-gene/7718) could be generated in the iPSCs prior to differentiation. The developmental trajectory of these knockout organoids would then be compared to wild-type controls using single-cell RNA sequencing at various time points. This would reveal if the loss of [ZNF165](/details-gene/7718) impairs the formation of specific pancreatic lineages, particularly alpha cells, and would identify the downstream transcriptional networks it controls. **Therapeutic Potential:** As an intracellular DNA-binding transcription factor, [ZNF165](/details-gene/7718) presents a challenging target for conventional small-molecule inhibitors. However, if its dysregulation is implicated in diseases characterized by aberrant cell differentiation, such as certain cancers or developmental disorders, it could be a candidate for emerging therapeutic modalities. For instance, therapies based on antisense oligonucleotides or targeted protein degraders (e.g., PROTACs) could be developed to modulate its activity. Given its role in establishing fundamental cell identities, any therapeutic intervention would require high specificity to avoid off-target effects on healthy progenitor or differentiated cell populations.

Genular Protein ID: 2354779545

Symbol: ZN165_HUMAN

Name: Zinc finger protein 165

UniProtKB Accession Codes:

P49910

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 2 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 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 4 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7490084

Title: Characterization of a novel zinc finger gene (ZNF165) mapping to 6p21 that is expressed specifically in testis.

PubMed ID: 7490084

DOI: 10.1006/geno.1995.1178

PubMed ID: 9244436

Title: Three genes encoding zinc finger proteins on human chromosome 6p21.3: members of a new subclass of the Kruppel gene family containing the conserved SCAN box domain.

PubMed ID: 9244436

DOI: 10.1006/geno.1997.4806

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

Sequence Information:

  • Length: 485
  • Mass: 55771
  • Checksum: 1265D859D1713AE8
  • Sequence:
    • MATEPKKAAA QNSPEDEGLL IVKIEEEEFI HGQDTCLQRS ELLKQELCRQ LFRQFCYQDS 
PGPREALSRL RELCCQWLKP EIHTKEQILE LLVLEQFLTI LPGDLQAWVH EHYPESGEEA 
VTILEDLERG TDEAVLQVQA HEHGQEIFQK KVSPPGPALN VKLQPVETKA HFDSSEPQLL 
WDCDNESENS RSMPKLEIFE KIESQRIISG RISGYISEAS GESQDICKSA GRVKRQWEKE 
SGESQRLSSA QDEGFGKILT HKNTVRGEII SHDGCERRLN LNSNEFTHQK SCKHGTCDQS 
FKWNSDFINH QIIYAGEKNH QYGKSFKSPK LAKHAAVFSG DKTHQCNECG KAFRHSSKLA 
RHQRIHTGER CYECNECGKS FAESSDLTRH RRIHTGERPF GCKECGRAFN LNSHLIRHQR 
IHTREKPYEC SECGKTFRVS SHLIRHFRIH TGEKPYECSE CGRAFSQSSN LSQHQRIHMR 
ENLLM