Details for: ZNF300

Gene ID: 91975

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: ZNF300

Ensembl ID: ENSG00000145908

Description: zinc finger protein 300

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 4.31
    rCSI 9.16%
    PRS 99.23
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.3
    rCSI 3.81%
    PRS 99.18
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.65
    rCSI 3.4%
    PRS 99.52
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.63
    rCSI 7.76%
    PRS 99.84
  • neural cell CL0002319
    CSI 2.43
    rCSI 9.18%
    PRS 98.21
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.13
    rCSI 3.76%
    PRS 98.87
  • neural progenitor cell CL0011020
    CSI 1.42
    rCSI 6.25%
    PRS 97.09

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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  • 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 [ZNF300](/details-gene/91975) is a protein-coding gene located on chromosome 5q33.1 that encodes Zinc Finger Protein 300, a member of the KRAB/C2H2 zinc finger protein family ([Link](https://doi.org/10.1016/j.bbaexp.2003.11.011)). Functional annotations indicate it acts as a DNA-binding transcription factor localized to the nucleus, specifically involved in regulating transcription by RNA polymerase II. Expression data highlights its significant role in neural development, showing high specificity for [progenitor cell](/details-cell/CL0011026)s, [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s, and other neural lineages. ## Cellular Roles and Expression Landscape The expression profile of [ZNF300](/details-gene/91975) strongly suggests a specialized function in the context of development and the nervous system. **Overall**, the gene shows its highest significance in immature and progenitor cell populations. It is a key marker for [progenitor cell](/details-cell/CL0011026) (CSI: 4.31) and various types of [neuroblast](/details-cell/CL0000338) (CSI: 3.30) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 2.65), indicating a potential role in maintaining pluripotency or guiding early lineage commitment. This role extends into more differentiated neural populations, with significant expression in [neural cell](/details-cell/CL0002319)s generally, as well as specific neuronal subtypes like the [cerebral cortex GABAergic interneuron](/details-cell/CL0010011) and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064). The consistent high significance in these related cell types points towards [ZNF300](/details-gene/91975) being a critical transcriptional regulator throughout neurogenesis, from the initial progenitor state to the specification of interneuron identity. ## Pathways and Molecular Function The molecular functions attributed to [ZNF300](/details-gene/91975) are consistent with its role as a transcriptional regulator. It is annotated with [Dna-binding transcription activator activity, rna polymerase ii-specific](/details-go/GO:0001228) and the capacity for [Sequence-specific dna binding](/details-go/GO:0043565), which are core functions for controlling gene expression programs. Its involvement in the Reactome pathways for [Gene expression (transcription)](https://reactome.org/content/detail/R-HSA-74160) and [Rna polymerase ii transcription](https://reactome.org/content/detail/R-HSA-73857) further solidifies this role. Cellular component annotations place the protein within the [Nucleus](/details-go/GO:0005634), specifically in the [Nucleoplasm](/details-go/GO:0005654) and [Nucleolus](/details-go/GO:0005730), which is the expected location for a transcription factor. This localization is likely reinforced by the interaction of its KRAB domain with KAP1, a known mechanism for tethering such proteins within the nucleus ([Link](https://doi.org/10.1007/s00018-013-1359-4)). This molecular machinery enables [ZNF300](/details-gene/91975) to execute its regulatory functions during the development of the cell types in which it is highly expressed. ## Research Directions The specific expression pattern of [ZNF300](/details-gene/91975) in neural progenitors and developing neurons positions it as a critical factor in neurogenesis, making its dysregulation a potential contributor to neurodevelopmental disorders or malignancies derived from these cell types. ### Proposed Hypotheses 1. **[ZNF300](/details-gene/91975) acts as a key regulator in maintaining the undifferentiated state of [neural progenitor cell](/details-cell/CL0011020)s, and its downregulation is a prerequisite for their terminal differentiation into mature neurons.** This is suggested by its peak expression in progenitor and neuroblast populations. 2. **Misexpression or mutation of [ZNF300](/details-gene/91975) disrupts the transcriptional fidelity of interneuron development, potentially contributing to the pathology of neurodevelopmental disorders characterized by an excitatory/inhibitory imbalance.** This hypothesis is based on its high significance in GABAergic interneuron lineages. ### Key Experimental Approach To test the hypothesis that [ZNF300](/details-gene/91975) regulates neural progenitor differentiation, a loss-of-function study could be performed. Specifically, a CRISPR-Cas9 knockout or an inducible shRNA knockdown of [ZNF300](/details-gene/91975) could be implemented in human iPSCs or primary [neural progenitor cell](/details-cell/CL0011020)s. These cells would then be subjected to a directed differentiation protocol. The effect of [ZNF300](/details-gene/91975) depletion could be assessed by single-cell RNA sequencing (scRNA-seq) at multiple time points to determine if its absence leads to premature or aberrant differentiation, or a shift in cell fate trajectories. ### Therapeutic Potential As an intracellular DNA-binding protein, [ZNF300](/details-gene/91975) is a challenging target for conventional small-molecule inhibitors. However, its highly specific expression in progenitor and neural lineages suggests potential therapeutic relevance. If its activity is found to be aberrantly high in neuroblastomas or other pediatric brain tumors that retain a progenitor-like phenotype, it could be a candidate for targeted degradation (e.g., PROTACs) or for nucleic acid-based therapies like antisense oligonucleotides designed to reduce its expression levels. The therapeutic strategy would focus on inhibition or downregulation to promote differentiation and halt uncontrolled proliferation in a pathological context.

Genular Protein ID: 3277292136

Symbol: ZN300_HUMAN

Name: Zinc finger protein 300

UniProtKB Accession Codes:

Q96RE9 A8MY91 B3KU35 B4DU78 F5GWS1 Q06DQ3 Q17RP3 Q5H9N5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 ExpressionAtlas 1 GO 11 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 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 Reactome 1 RefSeq 3 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14746915

Title: Identification and functional analysis of a novel human KRAB/C2H2 zinc finger gene ZNF300.

PubMed ID: 14746915

DOI: 10.1016/j.bbaexp.2003.11.011

PubMed ID: 17541838

Title: Molecular cloning and characterization of a novel splice variant of human ZNF300 gene, which expressed highly in testis.

PubMed ID: 17541838

DOI: 10.1080/10425170701243393

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 23665872

Title: Novel activity of KRAB domain that functions to reinforce nuclear localization of KRAB-containing zinc finger proteins by interacting with KAP1.

PubMed ID: 23665872

DOI: 10.1007/s00018-013-1359-4

Sequence Information:

  • Length: 604
  • Mass: 68743
  • Checksum: EABCF821E9FAC441
  • Sequence:
    • MMKSQGLVSF KDVAVDFTQE EWQQLDPSQR TLYRDVMLEN YSHLVSMGYP VSKPDVISKL 
EQGEEPWIIK GDISNWIYPD EYQADGRQDR KSNLHNSQSC ILGTVSFHHK ILKGVTRDGS 
LCSILKVCQG DGQLQRFLEN QDKLFRQVTF VNSKTVTEAS GHKYNPLGKI FQECIETDIS 
IQRFHKYDAF KKNLKPNIDL PSCYKSNSRK KPDQSFGGGK SSSQSEPNSN LEKIHNGVIP 
FDDNQCGNVF RNTQSLIQYQ NVETKEKSCV CVTCGKAFAK KSQLIVHQRI HTGKKPYDCG 
ACGKAFSEKF HLVVHQRTHT GEKPYDCSEC GKAFSQKSSL IIHQRVHTGE KPYECSECGK 
AFSQKSPLII HQRIHTGEKP YECRECGKAF SQKSQLIIHH RAHTGEKPYE CTECGKAFCE 
KSHLIIHKRI HTGEKPYKCA QCEEAFSRKT ELITHQLVHT GEKPYECTEC GKTFSRKSQL 
IIHQRTHTGE KPYKCSECGK AFCQKSHLIG HQRIHTGEKP YICTECGKAF SQKSHLPGHQ 
RIHTGEKPYI CAECGKAFSQ KSDLVLHQRI HTGERPYQCA ICGKAFIQKS QLTVHQRIHT 
VVKS