Details for: ZNF45

Gene ID: 7596

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: ZNF45

Ensembl ID: ENSG00000124459

Description: zinc finger protein 45

Cell Significance Landscape

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.08
    rCSI 2.48%
    PRS 93
  • innate lymphoid cell CL0001065
    CSI 2.07
    rCSI 4.28%
    PRS 92.79
  • suprabasal keratinocyte CL4033013
    CSI 1.91
    rCSI 3.11%
    PRS 80.73
  • basal cell of epidermis CL0002187
    CSI 1.56
    rCSI 2.76%
    PRS 79.08
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.23
    rCSI 1.49%
    PRS 84.68
  • helper T cell CL0000912
    CSI 1.16
    rCSI 1.65%
    PRS 93.35
  • melanocyte of skin CL1000458
    CSI 1.08
    rCSI 1.47%
    PRS 80.11

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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    • High
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    • 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 [ZNF45](/details-gene/7596) is a protein-coding gene located on chromosome 19q13.31 that encodes Zinc Finger Protein 45. As a member of the C2H2-type zinc finger protein family, it contains a KRAB (Krüppel-associated box) domain, which is a potent transcriptional repression module ([Link](https://doi.org/10.1159/000134490)). Functional annotations consistently point to its role as a DNA-binding transcription factor that regulates gene expression from its location within the [nucleoplasm](/details-cell/GO:0005654). Expression data indicates that [ZNF45](/details-gene/7596) is a significant gene in a surprisingly diverse set of cell types, including neuronal, immune, and epidermal lineages, suggesting a fundamental role in transcriptional regulation across multiple tissues. ## Cellular Roles and Expression Landscape The **Overall** expression profile of [ZNF45](/details-gene/7596) highlights its significance in disparate cellular contexts, suggesting it is not a simple lineage-specific marker but rather a more broadly utilized transcriptional regulator. Its highest significance is observed in [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 2.08), indicating a potential role in specifying or maintaining the identity of this neuronal subtype. Concurrently, [ZNF45](/details-gene/7596) shows strong significance in both the innate and adaptive immune systems, with high CSI values in [innate lymphoid cells](/details-cell/CL0001065) (CSI: 2.07) as well as in adaptive lymphocytes like [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 1.23) and [helper T cells](/details-cell/CL0000912) (CSI: 1.16). The expression in T cells is consistent with early studies identifying zinc finger protein expression in these cells ([Link](https://pubmed.ncbi.nlm.nih.gov/2288909/)). A third major site of [ZNF45](/details-gene/7596) expression is the skin, where it is highly significant in both proliferative [basal cells of the epidermis](/details-cell/CL0002187) (CSI: 1.56) and differentiating [suprabasal keratinocytes](/details-cell/CL4033013) (CSI: 1.91), as well as in pigment-producing [melanocytes of the skin](/details-cell/CL1000458) (CSI: 1.08). This broad expression pattern across cells originating from different germ layers (ectoderm and mesoderm) suggests that [ZNF45](/details-gene/7596) may regulate fundamental cellular processes or repress a common set of target genes across these distinct lineages. ## Pathways and Molecular Function The molecular function of [ZNF45](/details-gene/7596) is firmly established as a transcriptional regulator. Gene Ontology annotations describe it as having [DNA binding](/details-pathway/GO:0003677) and [DNA-binding transcription factor activity](/details-pathway/GO:0003700), with a primary role in the [regulation of DNA-templated transcription](/details-pathway/GO:0006355). Its function is further supported by its involvement in Reactome pathways such as [Gene expression (transcription)](/details-pathway/R-HSA-74160) and [RNA polymerase II transcription](/details-pathway/R-HSA-73857). The presence of a KRAB domain strongly implies that [ZNF45](/details-gene/7596) functions as a transcriptional repressor ([Link](https://doi.org/10.1159/000134490)). KRAB-zinc finger proteins typically recruit co-repressor complexes to specific genomic loci, leading to chromatin condensation and silencing of target genes. Furthermore, evidence suggests that [ZNF45](/details-gene/7596) may be regulated by post-translational modifications, as it has been identified as a target of SUMOylation, a process known to modulate the activity and localization of transcription factors ([Link](https://doi.org/10.1038/nsmb.3366)). ## Research Directions The broad yet specific expression pattern of [ZNF45](/details-gene/7596) raises several questions about its precise regulatory roles in different tissues. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis:** Given its high significance in both [basal cells of the epidermis](/details-cell/CL0002187) and [suprabasal keratinocytes](/details-cell/CL4033013), [ZNF45](/details-gene/7596) may function as a transcriptional repressor that gates the epidermal differentiation program. It could silence genes associated with terminal differentiation in the basal layer, and its modulated activity could be necessary for proper stratification. 2. **Hypothesis:** In the immune system, the high significance of [ZNF45](/details-gene/7596) in both [innate lymphoid cells](/details-cell/CL0001065) and T cells suggests it represses a common set of lineage-inappropriate genes or developmental pathways, thereby helping to maintain the distinct identities and functional states of these lymphoid cells. **Key Experiment:** To test the role of [ZNF45](/details-gene/7596) in keratinocyte differentiation (Hypothesis 1), a compelling experiment would be to use a CRISPR-Cas9 knockout or CRISPRi-mediated knockdown of [ZNF45](/details-gene/7596) in primary human keratinocytes. These engineered cells could then be used to generate 3D organotypic skin equivalents. The impact of [ZNF45](/details-gene/7596) loss could be assessed by examining epidermal morphology via histology and by measuring the expression of key differentiation markers (e.g., Keratin 14, Keratin 10, Loricrin, Filaggrin) using immunofluorescence and quantitative PCR. Complementary RNA-seq analysis would identify the direct and indirect downstream gene targets regulated by [ZNF45](/details-gene/7596) during this process. **Therapeutic Potential:** As an intracellular transcription factor, [ZNF45](/details-gene/7596) presents a challenging therapeutic target for conventional biologics like antibodies. However, its role as a transcriptional repressor suggests that its dysregulation could contribute to diseases characterized by altered cellular identity or differentiation, such as cancer or inflammatory skin disorders (e.g., psoriasis). If [ZNF45](/details-gene/7596) were found to repress tumor suppressor genes, its inhibition could be a therapeutic goal, potentially achievable with small molecule inhibitors. Conversely, if it represses oncogenes, developing strategies to enhance its function or expression might be beneficial. Its widespread expression pattern, however, indicates that any systemic therapeutic intervention would need to be highly specific to avoid off-target effects in healthy tissues.

Genular Protein ID: 679161752

Symbol: ZNF45_HUMAN

Name: Zinc finger protein 45

UniProtKB Accession Codes:

Q02386 P17016 P78472 Q9P1U9

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 6 Ensembl 3 ExpressionAtlas 1 GO 4 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 2 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 Reactome 1 RefSeq 16 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9067431

Title: Complete coding sequence, exon/intron arrangement and chromosome location of ZNF45, a KRAB-domain-containing gene.

PubMed ID: 9067431

DOI: 10.1159/000134490

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: 1559709

Title: The identification and characterization of KRAB-domain-containing zinc finger proteins.

PubMed ID: 1559709

DOI: 10.1016/0888-7543(92)90451-w

PubMed ID: 2288909

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

PubMed ID: 2288909

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: 682
  • Mass: 78242
  • Checksum: 9C8E536EB00FCE8B
  • Sequence:
    • MTKSKEAVTF KDVAVVFSEE ELQLLDLAQR KLYRDVMLEN FRNVVSVGHQ STPDGLPQLE 
REEKLWMMKM ATQRDNSSGA KNLKEMETLQ EVGLRYLPHE ELFCSQIWQQ ITRELIKYQD 
SVVNIQRTGC QLEKRDDLHY KDEGFSNQSS HLQVHRVHTG EKPYKGEHCV KSFSWSSHLQ 
INQRAHAGEK PYKCEKCDNA FRRFSSLQAH QRVHSRAKSY TNDASYRSFS QRSHLPHHQR 
VPTGENPYKY EECGRNVGKS SHCQAPLIVH TGEKPYKCEE CGVGFSQRSY LQVHLKVHTG 
KKPYKCEECG KSFSWRSRLQ AHERIHTGEK PYKCNACGKS FSYSSHLNIH CRIHTGEKPY 
KCEECGKGFS VGSHLQAHQI SHTGEKPYKC EECGKGFCRA SNLLDHQRGH TGEKPYQCDA 
CGKGFSRSSD FNIHFRVHTG EKPYKCEECG KGFSQASNLL AHQRGHTGEK PYKCGTCGKG 
FSRSSDLNVH CRIHTGEKPY KCERCGKAFS QFSSLQVHQR VHTGEKPYQC AECGKGFSVG 
SQLQAHQRCH TGEKPYQCEE CGKGFCRASN FLAHRGVHTG EKPYRCDVCG KRFRQRSYLQ 
AHQRVHTGER PYKCEECGKV FSWSSYLQAH QRVHTGEKPY KCEECGKGFS WSSSLIIHQR 
VHADDEGDKD FPSSEDSHRK TR