Details for: ZNF500

Gene ID: 26048

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: ZNF500

Ensembl ID: ENSG00000103199

Description: zinc finger protein 500

Cell Significance Landscape

Associated with

Significant Cells

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

  • regulatory T cell CL0000815
    CSI 15.8
    rCSI 18.32%
    PRS 99.28
  • chondrocyte CL0000138
    CSI 15.59
    rCSI 24.79%
    PRS 99.65
  • pericyte CL0000669
    CSI 13.15
    rCSI 35.02%
    PRS 98.76
  • innate lymphoid cell CL0001065
    CSI 12.2
    rCSI 25.19%
    PRS 99.41
  • conventional dendritic cell CL0000990
    CSI 11.65
    rCSI 9.73%
    PRS 99.3
  • basal cell of epidermis CL0002187
    CSI 11.12
    rCSI 19.72%
    PRS 96.82
  • helper T cell CL0000912
    CSI 11
    rCSI 15.56%
    PRS 99.48
  • mast cell CL0000097
    CSI 10.89
    rCSI 23.51%
    PRS 99.08
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 10.89
    rCSI 13.19%
    PRS 97.7
  • melanocyte of skin CL1000458
    CSI 10.16
    rCSI 13.85%
    PRS 97.79
  • suprabasal keratinocyte CL4033013
    CSI 8.74
    rCSI 14.26%
    PRS 98.29
  • interneuron CL0000099
    CSI 8.06
    rCSI 16.19%
    PRS 99.97
  • astrocyte of the cerebral cortex CL0002605
    CSI 5.94
    rCSI 13.32%
    PRS 99.84
  • ciliated epithelial cell CL0000067
    CSI 5.87
    rCSI 5.16%
    PRS 99.74
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 5.64
    rCSI 9.96%
    PRS 99.85
  • peripheral nervous system neuron CL2000032
    CSI 5.45
    rCSI 7.43%
    PRS 99.83
  • endothelial cell of vascular tree CL0002139
    CSI 4.93
    rCSI 26.97%
    PRS 99.66
  • cytotoxic T cell CL0000910
    CSI 2.52
    rCSI 14.47%
    PRS 99.56

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.

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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 [ZNF500](/details-gene/26048) is a protein-coding gene located on chromosome 16p13.3 that encodes Zinc Finger Protein 500. Functional annotations consistently identify it as a nuclear protein with a primary role in the regulation of gene expression. Specifically, it acts as a DNA-binding transcription factor involved in pathways mediated by RNA polymerase II. Expression data reveals that [ZNF500](/details-gene/26048) has high significance in a surprisingly diverse range of cell types, spanning the immune, mesenchymal, and ectodermal lineages. Its prominence in cells such as [regulatory T cells](/details-cell/CL0000815) and [chondrocytes](/details-cell/CL0000138) suggests it may play pleiotropic roles in immune suppression, skeletal tissue maintenance, and epidermal homeostasis. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ZNF500](/details-gene/26048) is notable for its breadth, showing high significance in functionally distinct cell populations, which suggests it is not a simple lineage marker but a regulator of specific programs within multiple contexts. A prominent role in the immune system is suggested by its high significance in several lymphocyte populations. It is a top marker in [regulatory T cells](/details-cell/CL0000815) (CSI: 15.80), [innate lymphoid cells](/details-cell/CL0001065) (CSI: 12.20), [helper T cells](/details-cell/CL0000912) (CSI: 11.00), and [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 10.89). Its expression in these cells, particularly suppressive T cell subsets, points towards a potential function in modulating adaptive and innate immune responses. Concurrently, [ZNF500](/details-gene/26048) exhibits equally high significance in non-hematopoietic, structural cell types. It is exceptionally significant in [chondrocytes](/details-cell/CL0000138) (CSI: 15.59), the primary cells of cartilage, and [pericytes](/details-cell/CL0000669) (CSI: 13.15), which are crucial for vascular stability. This dual expression pattern suggests a functional role in both immune regulation and the maintenance of connective tissues. Furthermore, the gene shows relevance in epidermal and neural contexts, with significant expression in [basal cells of the epidermis](/details-cell/CL0002187) (CSI: 11.12), [melanocytes of skin](/details-cell/CL1000458) (CSI: 10.16), and various [interneurons](/details-cell/CL0000099) (CSI: 8.06). This wide-ranging expression landscape indicates that [ZNF500](/details-gene/26048) likely regulates transcriptional networks essential for the specialized functions of these diverse cell types. The initial identification of this gene was through large-scale cDNA sequencing projects ([Link](https://doi.org/10.1093/dnares/5.1.31), [Link](https://doi.org/10.1038/ng1285)). ## Pathways and Molecular Function The molecular functions of [ZNF500](/details-gene/26048) are firmly rooted in transcriptional control, consistent with its characterization as a zinc finger protein. Gene Ontology annotations indicate that it operates within the [nucleus](/details-cell/GO:0005634) where it participates in the [regulation of transcription by rna polymerase ii](/details-cell/GO:0006357). Its core molecular activities include [dna-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981) and [metal ion binding](/details-cell/GO:0046872), the latter being essential for the structural integrity of its zinc finger domains. Reactome pathway analysis reinforces this role, placing [ZNF500](/details-gene/26048) within the fundamental processes of [Gene expression (transcription)](/details-cell/R-HSA-74160) and specifically [Rna polymerase ii transcription](/details-cell/R-HSA-73857). This function as a transcriptional regulator provides a plausible mechanism for its broad impact across various cell lineages. It likely achieves its cell-specific effects by binding to distinct cis-regulatory elements to control the expression of downstream genes that define the functional identity of cells as different as [T cells](/details-cell/CL0000815) and [chondrocytes](/details-cell/CL0000138). ## Research Directions The most intriguing aspect of [ZNF500](/details-gene/26048) is its high significance in functionally disparate cell types, which raises important questions about its specific roles and regulatory mechanisms in health and disease. **Proposed Hypotheses:** 1. Given its high CSI in [regulatory T cells](/details-cell/CL0000815), it is hypothesized that **[ZNF500](/details-gene/26048) is a crucial transcription factor for maintaining the suppressive function and lineage stability of Tregs**, possibly acting downstream of or in concert with the master regulator FOXP3. 2. The exceptionally high significance in [chondrocytes](/details-cell/CL0000138) suggests a distinct role in skeletal biology. A second hypothesis is that **[ZNF500](/details-gene/26048) is a key regulator of chondrocyte homeostasis, controlling the expression of genes essential for extracellular matrix synthesis (e.g., collagens, aggrecan) and preventing osteoarthritic degradation.** 3. The gene's broad expression in diverse cells like [pericytes](/details-cell/CL0000669), [basal cells](/details-cell/CL0002187), and [T cells](/details-cell/CL0000815) may indicate a role in a shared fundamental process. Therefore, it is also hypothesized that **[ZNF500](/details-gene/26048) orchestrates a transcriptional program related to cellular quiescence, stress resistance, or metabolic adaptation common to these long-lived or highly regulated cell populations.** **Key Experimental Approach:** To test the first hypothesis regarding the role of [ZNF500](/details-gene/26048) in [regulatory T cell](/details-cell/CL0000815) function, a conditional knockout mouse model could be generated (e.g., *Zfp500fl/fl;Foxp3Cre*). In these mice, [ZNF500](/details-gene/26048) would be specifically deleted in the Treg lineage. The impact on Treg development, stability, and suppressive capacity could be evaluated using flow cytometry and in vitro suppression assays. Furthermore, inducing an autoimmune disease model (e.g., experimental autoimmune encephalomyelitis or colitis) in these mice would reveal its in vivo importance. Mechanistically, comparing the transcriptomes (RNA-seq) and ZNF500 binding sites (ChIP-seq) of wild-type and knockout Tregs would identify its direct target genes and its position within the Treg regulatory network. **Therapeutic Potential:** As an intracellular transcription factor, [ZNF500](/details-gene/26048) is a difficult target for conventional biologics or small molecules. However, should it be identified as a critical dependency factor in a disease, its therapeutic potential could be significant. For instance, if its overexpression contributes to Treg-mediated immunosuppression in cancer, strategies to inhibit its function or expression could enhance anti-tumor immunity. Conversely, if its loss of function in chondrocytes contributes to osteoarthritis, activating its transcriptional program could be beneficial. Its broad expression profile means that any therapeutic intervention would require high cell-type specificity, potentially through targeted delivery systems or by targeting a unique downstream effector, to minimize off-target effects.

Genular Protein ID: 2549326828

Symbol: ZN500_HUMAN

Name: Zinc finger protein 500

UniProtKB Accession Codes:

O60304 A8K6X7 B4DNN9 Q0VAL2 Q96CQ8 Q9BTG0

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9628581

Title: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9628581

DOI: 10.1093/dnares/5.1.31

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

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: 480
  • Mass: 53674
  • Checksum: 9AB0F456F2DC5580
  • Sequence:
    • MATVPGLQPL PTLEQDLEQE EILIVKVEED FCLEEEPSVE TEDPSPETFR QLFRLFCYQE 
VAGPREALSR LWELCCRWLR PELRTKEQIL ELLVLEQFLT VLPGEIQARV REQQPESGEE 
AVVLVEGLQR KPRKHRQRGS ELLSDDEVPL GIGGQFLKHQ AEAQPEDLSL EEEARFSSQQ 
PPAQLSHRPQ RGPLLWPERG PPAPRHQEMA SASPFLSAWS QVPVNLEDVA VYLSGEEPRC 
MDPAQRDAPL ENEGPGIQLE DGGDGREDAP LRMEWYRVLS ARCQGPGHPL PGQRPAPVRG 
LVRPDQPRGG PPPGRRASHG ADKPYTCPEC GKGFSKTSHL TKHQRTHTGE RPYKCLVCGK 
GFSDRSNFST HQRVHTGEKP YPCPECGKRF SQSSSLVIHR RTHSGERPYA CTQCGKRFNN 
SSHFSAHRRT HTGEKPYTCP ACGRGFRRGT DLHKHQRTHM GAGSLPTLQP VAPGGPGAKA