Details for: ZNF14

Gene ID: 7561

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: ZNF14

Ensembl ID: ENSG00000105708

Description: zinc finger protein 14

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Gene expression (transcription)
    (R-HSA-74160)
  • Generic transcription pathway
    (R-HSA-212436)
  • Rna polymerase ii transcription
    (R-HSA-73857)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Metal ion binding
    (GO:0046872)
  • Nucleus
    (GO:0005634)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii transcription regulatory region sequence-specific dna binding
    (GO:0000977)

Significant Cells

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

  • interneuron CL0000099
    CSI 4.01
    rCSI 8.05%
    PRS 95.39
  • cerebral cortex endothelial cell CL1001602
    CSI 2.63
    rCSI 4.54%
    PRS 95.61
  • retinal bipolar neuron CL0000748
    CSI 2.61
    rCSI 4.88%
    PRS 93.69
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.48
    rCSI 2.96%
    PRS 92.7
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.32
    rCSI 3%
    PRS 93.19
  • ependymal cell CL0000065
    CSI 2.29
    rCSI 4.65%
    PRS 88.39
  • renal beta-intercalated cell CL0002201
    CSI 2.11
    rCSI 5.04%
    PRS 97.29
  • regulatory T cell CL0000815
    CSI 2.01
    rCSI 2.33%
    PRS 92.52
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.74
    rCSI 3.91%
    PRS 92.98
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.61
    rCSI 2.71%
    PRS 92.94
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.57
    rCSI 2.52%
    PRS 92.95
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.55
    rCSI 2.74%
    PRS 92.61
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.35
    rCSI 3.42%
    PRS 95.48
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.01
    rCSI 2.45%
    PRS 91.26
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.74
    rCSI 2.79%
    PRS 92.4
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.73
    rCSI 2.64%
    PRS 91.44
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.48
    rCSI 2.8%
    PRS 92.66

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 [ZNF14](/details-gene/7561), or Zinc Finger Protein 14, is a protein-coding gene located on chromosome 19p13.11. Functionally, it is annotated as a DNA-binding transcription factor that specifically participates in the regulation of transcription by RNA polymerase II ([GO:0006357](https://www.ebi.ac.uk/QuickGO/term/GO:0006357)). Expression data highlights its significant role within the central nervous system, where it shows the highest significance in various neuronal subtypes, particularly [interneuron](/details-cell/CL0000099)s. Its expression is also noted in other diverse cell types, including endothelial cells, glial cells, and specific immune and epithelial populations, suggesting it plays a fundamental role in regulating gene expression across multiple cellular contexts. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ZNF14](/details-gene/7561) indicates a primary role in the central nervous system. The gene exhibits its highest cell-type significance in [interneuron](/details-cell/CL0000099) (CSI: 4.01), with strong signals also observed in other neuronal populations such as [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 2.61) and multiple subtypes of GABAergic cortical interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [sst GABAergic cortical interneuron](/details-cell/CL4023017). This widespread and high significance across diverse neuronal types suggests [ZNF14](/details-gene/7561) may be involved in establishing or maintaining fundamental neuronal transcriptional programs. Beyond neurons, [ZNF14](/details-gene/7561) is also a significant marker in several non-neuronal cell types. It shows notable expression in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.63) and glial cells like [ependymal cell](/details-cell/CL0000065) (CSI: 2.29) and [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 1.74). Interestingly, the gene is also significantly expressed outside the nervous system in cell types such as [renal beta-intercalated cell](/details-cell/CL0002201) (CSI: 2.11) and [regulatory T cell](/details-cell/CL0000815) (CSI: 2.01). This latter observation is consistent with early reports of zinc finger domain-containing genes being expressed in human T cells [Link](https://pubmed.ncbi.nlm.nih.gov/2288909). This broad but specific expression pattern suggests that [ZNF14](/details-gene/7561) may regulate core transcriptional machinery while possibly activating distinct gene sets depending on the cellular context. ## Pathways and Molecular Function The functional annotations for [ZNF14](/details-gene/7561) are consistent with its role as a nuclear protein ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) involved in the fundamental process of gene expression. Its molecular functions are centered on its ability to interact with DNA and regulate transcription, specifically through [DNA-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO0000981) ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)) and [RNA polymerase II transcription regulatory region sequence-specific DNA binding](/details-go/GO0000977) ([GO:0000977](https://www.ebi.ac.uk/QuickGO/term/GO:0000977)). The zinc finger domains characteristic of this protein family facilitate its [metal ion binding](/details-go/GO0046872) ([GO:0046872](https://www.ebi.ac.uk/QuickGO/term/GO:0046872)) capacity, which is essential for its structural integrity and DNA-binding activity. At the pathway level, [ZNF14](/details-gene/7561) is a component of the core transcriptional machinery, as indicated by its involvement in Reactome pathways such as [Gene expression (transcription)](https://reactome.org/content/detail/R-HSA-74160) ([R-HSA-74160](https://reactome.org/content/detail/R-HSA-74160)), the [Generic transcription pathway](https://reactome.org/content/detail/R-HSA-212436) ([R-HSA-212436](https://reactome.org/content/detail/R-HSA-212436)), and [RNA polymerase II transcription](https://reactome.org/content/detail/R-HSA-73857) ([R-HSA-73857](https://reactome.org/content/detail/R-HSA-73857)). This central role in transcription regulation provides a molecular basis for its high expression in metabolically active and functionally complex cells like neurons and [regulatory T cell](/details-cell/CL0000815)s, which require precise control over their gene expression profiles. ## Research Directions The specific and significant expression of [ZNF14](/details-gene/7561) across distinct cell lineages, particularly within the nervous and immune systems, prompts several lines of inquiry. ### Proposed Hypotheses: 1. **[ZNF14](/details-gene/7561) is a master regulator of interneuron subtype identity.** Given its exceptionally high CSI score in [interneuron](/details-cell/CL0000099)s and related GABAergic neuronal subtypes, it is plausible that [ZNF14](/details-gene/7561) binds to key regulatory elements to activate or repress gene networks that define the unique functional properties of these inhibitory neurons. 2. **[ZNF14](/details-gene/7561) plays a context-dependent role in maintaining the suppressive function of [regulatory T cell](/details-cell/CL0000815)s.** The significant expression in Tregs, a cell type functionally distinct from neurons, suggests that [ZNF14](/details-gene/7561) may regulate a different suite of target genes in this lineage, potentially including those critical for immune tolerance, such as *FOXP3* or its downstream effectors. ### Suggested Experimental Approach: To test the hypothesis that **[ZNF14](/details-gene/7561) is critical for interneuron development and function**, a conditional knockout (cKO) mouse model could be generated. By crossing a floxed *Zfp14* mouse with a Cre-driver line specific to interneuron progenitors (e.g., *Nkx2-1-Cre* or *Dlx5/6-Cre*), the gene can be selectively deleted in this lineage. Subsequent analysis using single-cell RNA sequencing (scRNA-seq) on the developing and adult cortex would reveal defects in interneuron migration, subtype specification, and maturation. Furthermore, chromatin immunoprecipitation sequencing (ChIP-seq) for ZNF14 in sorted interneurons would identify its direct target genes, clarifying the specific pathways it regulates to control their identity. ### Therapeutic Potential: As an intracellular DNA-binding transcription factor, [ZNF14](/details-gene/7561) represents a challenging therapeutic target for conventional small-molecule inhibitors. Its fundamental role in transcription suggests that systemic inhibition could lead to significant off-target effects. However, if its dysregulation is linked to specific neurological or autoimmune disorders associated with the cell types in which it is highly expressed (e.g., epilepsy or T-cell-mediated diseases), strategies based on targeting its downstream effectors might be more viable. Moreover, the development of technologies like antisense oligonucleotides or targeted protein degraders could potentially offer a path to modulate its activity in a more controlled manner in the future. Any therapeutic strategy would likely focus on inhibition, assuming a gain-of-function or over-expression context in a disease state.

Genular Protein ID: 1753952798

Symbol: ZNF14_HUMAN

Name: Zinc finger protein 14

UniProtKB Accession Codes:

P17017 B9EGA4 Q9ULZ5

Database IDs:

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 5 Ensembl 1 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 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 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 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: 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

PubMed ID: 2288909

Title: Multiple genes encoding zinc finger domains are expressed in human T cells.

PubMed ID: 2288909

Sequence Information:

  • Length: 642
  • Mass: 75353
  • Checksum: 806374FBDC480CE3
  • Sequence:
    • MDSVSFEDVA VNFTLEEWAL LDSSQKKLYE DVMQETFKNL VCLGKKWEDQ DIEDDHRNQG 
KNRRCHMVER LCESRRGSKC GETTSQMPNV NINKETFTGA KPHECSFCGR DFIHHSSLNR 
HMRSHTGQKP NEYQEYEKQP CKCKAVGKTF SYHHCFRKHE RTHTGVKPYE CKQCGKAFIY 
YQPFQRHERT HAGQKPYECK QCGKTFIYYQ SFQKHAHTGK KPYECKQCGK AFICYQSFQR 
HKRTHTGEKP YECKQCGKAF SCPTYFRTHE RTHTGEKPYK CKECGKAFSF LSSFRRHKRT 
HSGEKPYECK ECGKAFFYSA SFRAHVIIHT GARPYKCKEC GKAFNSSNSC RVHERTHIGE 
KPYECKRCGK SFSWSISLRL HERTHTGEKP YECKQCHKTF SFSSSLREHE TTHTGEKPYE 
CKQCGKTFSF SSSLQRHERT HNAEKPYECK QCGKAFRCSS YFRIHERSHT GEKPYECKQC 
GKVFIRSSSF RLHERTHTGE KPYECKLCGK TFSFSSSLRE HEKIHTGNKP FECKQCGKAF 
LRSSQIRLHE RTHTGEKPYQ CKQCGKAFIS SSKFRMHERT HTGEKPYRCK QCGKAFRFSS 
SVRIHERSHT GEKPYECKQC GKAFISSSHF RLHERTHMGE KV