Details for: ZNF354B

Gene ID: 117608

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: ZNF354B

Ensembl ID: ENSG00000178338

Description: zinc finger protein 354B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 3.55
    rCSI 15.62%
    PRS 94.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.62
    rCSI 3.26%
    PRS 96.11
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.59
    rCSI 3.1%
    PRS 96.46
  • extravillous trophoblast CL0008036
    CSI 2.53
    rCSI 3.14%
    PRS 98.43
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.3
    rCSI 2.97%
    PRS 97
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.92
    rCSI 3.38%
    PRS 96.61
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.8
    rCSI 3.02%
    PRS 96.89
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.18
    rCSI 3.41%
    PRS 98.83

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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  • 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 [ZNF354B](/details-gene/117608) is a protein-coding gene that encodes Zinc Finger Protein 354B. Functional annotations strongly indicate that it operates as a nuclear transcription factor, specifically a DNA-binding transcriptional corepressor involved in the negative regulation of RNA polymerase II-mediated transcription. Expression data from the **Overall** context reveals its highly specific and significant role within the central nervous system, where it is a prominent marker for [neural progenitor cells](/details-cell/CL0011020) and various subtypes of GABAergic cortical interneurons. This expression pattern, combined with its molecular function, suggests a critical role for [ZNF354B](/details-gene/117608) in regulating gene expression programs during neurodevelopment and in maintaining the identity of specific neuronal populations. ## Cellular Roles and Expression Landscape The expression profile of [ZNF354B](/details-gene/117608) points to a specialized function primarily within the nervous system. The gene shows its highest significance in [neural progenitor cells](/details-cell/CL0011020) (CSI: 3.55), suggesting an important role during the early stages of neural development. Following this, [ZNF354B](/details-gene/117608) is a defining marker for several distinct classes of inhibitory interneurons in the cortex, including [pvalb GABAergic cortical interneurons](/details-cell/CL4023018), [VIP GABAergic cortical interneurons](/details-cell/CL4023016), [sst GABAergic cortical interneurons](/details-cell/CL4023017), and [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011). Its consistent high significance across these functionally diverse interneuron populations suggests it may be a core component of the transcriptional machinery that establishes or maintains the GABAergic phenotype. Beyond the nervous system, [ZNF354B](/details-gene/117608) also shows notable expression in [extravillous trophoblasts](/details-cell/CL0008036) and [microcirculation associated smooth muscle cells](/details-cell/CL0008035), indicating potential secondary roles in placental development and vascular regulation, respectively. The full-length cDNA for this gene was characterized as part of the Mammalian Gene Collection project [Link](https://doi.org/10.1101/gr.2596504). ## Pathways and Molecular Function Functionally, [ZNF354B](/details-gene/117608) is annotated as a nuclear protein ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) that participates directly in the regulation of gene expression. Its molecular functions are centered on its ability to interact with DNA and chromatin. It is characterized as having [DNA-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981) and [transcription corepressor activity](/details-cell/GO:0003714). This dual function is consistent with its involvement in the [negative regulation of transcription by rna polymerase ii](/details-cell/GO:0000122). These molecular activities are integral to broader biological processes, including 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). The role of [ZNF354B](/details-gene/117608) as a transcriptional corepressor aligns perfectly with its high significance in [neural progenitor cells](/details-cell/CL0011020), where the precise suppression of specific genetic programs is essential for guiding proper cellular differentiation and lineage commitment. Post-translational modification of the protein by SUMOylation has also been observed [Link](https://doi.org/10.1038/nsmb.3366). ## Research Directions The specific expression pattern and annotated function of [ZNF354B](/details-gene/117608) give rise to several testable hypotheses regarding its role in biology and disease. 1. **Hypothesis 1:** Given its high significance in multiple, distinct subtypes of cortical interneurons, [ZNF354B](/details-gene/117608) may function as a master regulator that actively represses a common set of non-GABAergic genes, thereby stabilizing the identity of these inhibitory neurons. 2. **Hypothesis 2:** The top expression of [ZNF354B](/details-gene/117608) in [neural progenitor cells](/details-cell/CL0011020), coupled with its corepressor activity, suggests it is critical for neural fate specification by suppressing genes associated with alternative developmental lineages (e.g., glial or ectodermal fates) during early neurogenesis. A key experiment to test the second hypothesis would be to use a CRISPR interference (CRISPRi) system to specifically knockdown [ZNF354B](/details-gene/117608) expression in human induced pluripotent stem cells (iPSCs) undergoing directed differentiation toward cortical neurons. Single-cell RNA sequencing (scRNA-seq) could then be performed at various time points during the differentiation protocol. This would allow for a direct assessment of whether the loss of [ZNF354B](/details-gene/117608) function leads to a failure in silencing non-neuronal genes and results in aberrant cell fate choices or developmental arrest. From a therapeutic standpoint, [ZNF354B](/details-gene/117608) is a challenging target. As an intracellular DNA-binding protein, it is not readily accessible to conventional antibody-based therapies or most small molecules. However, its specific expression pattern in developing and mature neurons suggests that its dysregulation could be implicated in neurodevelopmental or psychiatric disorders characterized by interneuron dysfunction. Therefore, it may serve as a valuable biomarker or a potential target for gene-based therapies in specific, well-defined neurological conditions rather than a candidate for pharmacological inhibition.

Genular Protein ID: 697701458

Symbol: Z354B_HUMAN

Name: Zinc finger protein 354B

UniProtKB Accession Codes:

Q96LW1 A8K0V2 Q5U5Z4

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 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 8 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 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 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 612
  • Mass: 70529
  • Checksum: D1E94FD6B22305B0
  • Sequence:
    • MAAGQREARP QVSLTFEDVA VLFTWDEWRK LAPSQRNLYR DVMLENYRNL VSLGLSFTKP 
KVISLLQQGE DPWEVEKDSS GVSSLGCKST PKMTKSTQTQ DSFQEQIRKR LKRDEPWNFI 
SERSCIYEEK LKKQQDKNEN LQIISVAHTK ILTVDRSHKN VEFGQNFYLK SVFIKQQRFA 
KEKTPSKCEI QRNSFKQNSN LLNQSKIKTA EKRYKCSTCE KAFIHNSSLR KHQKNHTGEK 
LFKCKECLKA FSQSSALIQH QRTHTGEKPY ICKECGKAFS HSASLCKHLR THTVEKCYRC 
KECGKSFSRR SGLFIHQKIH AQENPHKYNP GRKASSYSTS LSGSQKIHLR KKSYLCNECG 
NTFKSSSSLR YHQRIHTGEK PFKCSECGRA FSQSASLIQH ERIHTGEKPY RCNECGKGFT 
SISRLNRHRI IHTGEKLYNC NECGKALSSH STLIIHERIH TGEKPCKCKV CGKAFRQSSA 
LIQHQRMHTG ERPYKCNECD KTFRCNSSLS NHQRIHTGEK PYRCLECGMS FGQSAALIQH 
QRIHTGEKPF KCNTCGKTFR QSSSLIAHQR IHTGEKPYEC NACGKLFSQR SSLTNHYKIH 
IEEDSLKADL HV