Details for: ZSCAN21

Gene ID: 7589

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: ZSCAN21

Ensembl ID: ENSG00000166529

Description: zinc finger and SCAN domain containing 21

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Cell differentiation
    (GO:0030154)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Male meiosis i
    (GO:0007141)
  • Metal ion binding
    (GO:0046872)
  • Nucleus
    (GO:0005634)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Regulation of dna-templated transcription
    (GO:0006355)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Spermatogenesis
    (GO:0007283)

Significant Cells

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

  • progenitor cell CL0011026
    CSI 5.59
    rCSI 11.88%
    PRS 95.35
  • interneuron CL0000099
    CSI 3.9
    rCSI 7.84%
    PRS 96.29
  • neural crest cell CL0011012
    CSI 3.78
    rCSI 2.98%
    PRS 96.68
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.12
    rCSI 2.73%
    PRS 94.71
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.98
    rCSI 3.32%
    PRS 94.35
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.67
    rCSI 2.03%
    PRS 86.45
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.61
    rCSI 2.85%
    PRS 94.12

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 [ZSCAN21](/details-gene/7589) (zinc finger and SCAN domain containing 21) is a protein-coding gene located on chromosome 7q22.1. It encodes a putative transcription factor characterized by the presence of a SCAN domain and zinc finger motifs, consistent with a role in DNA binding and transcriptional regulation. Functional annotations strongly implicate [ZSCAN21](/details-gene/7589) in the positive regulation of transcription, cell differentiation, and spermatogenesis. Expression data highlights its significant role in developmental and neural contexts, with particularly high significance in [progenitor cells](/details-cell/CL0011026), [neural crest cells](/details-cell/CL0011012), and various subtypes of inhibitory [interneurons](/details-cell/CL0000099). A potential link to renal-cell carcinoma has also been reported, where it was identified as an antigen recognized by autologous antibodies ([OMIM](/details-gene/601261)) [Link](https://doi.org/10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5). ## Cellular Roles and Expression Landscape The expression profile of [ZSCAN21](/details-gene/7589) suggests a highly specialized function in cellular development and the nervous system. **Overall**, the gene shows its highest significance in precursor cell populations, including [progenitor cell](/details-cell/CL0011026) (CSI: 5.59) and [neural crest cell](/details-cell/CL0011012) (CSI: 3.78), which is consistent with its annotated role in [cell differentiation](/details-gene/GO:0030154). A predominant theme in its expression is a strong association with specific neuronal subtypes, particularly inhibitory interneurons. It is a significant marker in the broad [interneuron](/details-cell/CL0000099) category (CSI: 3.90) and more specific subtypes such as [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.12), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 1.98), and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 1.61). This pattern suggests [ZSCAN21](/details-gene/7589) may be a key transcriptional regulator involved in establishing or maintaining the identity and function of these specific GABAergic neurons. Interestingly, a moderate but notable significance is also observed in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 1.67), indicating a potential secondary role within a subset of the adaptive immune system. ## Pathways and Molecular Function The molecular function of [ZSCAN21](/details-gene/7589) is centered on transcriptional control, as supported by multiple Gene Ontology annotations. It is predicted to have [DNA-binding transcription activator activity, rna polymerase ii-specific](/details-gene/GO:0001228) and [rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-gene/GO:0000978). Its function is localized to the [nucleus](/details-gene/GO:0005634), which is the expected subcellular compartment for a transcription factor. Biologically, [ZSCAN21](/details-gene/7589) is implicated in several key processes: * **Transcriptional Regulation:** It is involved in both the general [regulation of dna-templated transcription](/details-gene/GO:0006355) and the more specific [positive regulation of transcription by rna polymerase ii](/details-gene/GO:0045944). * **Development and Differentiation:** Its role in [cell differentiation](/details-gene/GO:0030154) aligns with its high expression in progenitor and neural crest cells. * **Reproduction:** A highly specific role is suggested by its annotation in [spermatogenesis](/details-gene/GO:0007283) and [male meiosis i](/details-gene/GO:0007141), indicating it may be crucial for male germ cell development. * **Binding Activities:** The protein is also annotated with [metal ion binding](/details-gene/GO:0046872), characteristic of zinc finger proteins, and general [protein binding](/details-gene/GO:0005515), suggesting it may function as part of larger protein complexes to regulate gene expression. The initial sequencing and characterization of this gene were part of large-scale cDNA projects aimed at cataloging human genes [Link](https://doi.org/10.1101/gr.gr1547r), [Link](https://doi.org/10.1101/gr.2596504), and mapping the human genome [Link](https://doi.org/10.1126/science.1083423). ## Research Directions The available data points to several key areas for future investigation into the function of [ZSCAN21](/details-gene/7589). Its specific expression pattern and functional annotations lead to several testable hypotheses. **Proposed Hypotheses:** 1. Given its high significance in progenitor cells and multiple interneuron subtypes, [ZSCAN21](/details-gene/7589) acts as a fate-determining transcription factor that drives the differentiation of neural progenitors specifically towards GABAergic interneuron lineages. 2. Based on the strong GO annotations for [spermatogenesis](/details-gene/GO:0007283) and [male meiosis i](/details-gene/GO:0007141), [ZSCAN21](/details-gene/7589) is essential for the progression of male germ cells through meiosis, and its loss would lead to male infertility. 3. The identification of [ZSCAN21](/details-gene/7589) as an antigen in renal-cell carcinoma suggests that it is a cancer-testis antigen, a class of proteins normally restricted to germ cells but ectopically expressed in tumors, making it a target for the immune system [Link](https://doi.org/10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5). **Experimental Approach:** To test the hypothesis regarding its role in interneuron development, an *in vitro* differentiation model using human pluripotent stem cells (hPSCs) could be employed. * **Model:** Direct differentiation of a CRISPR-Cas9 generated [ZSCAN21](/details-gene/7589)-knockout hPSC line and an isogenic wild-type control line into cortical interneurons. * **Analysis:** At various time points during differentiation, cell populations would be analyzed using single-cell RNA sequencing (scRNA-seq) to map developmental trajectories and identify points of divergence. * **Validation:** The final neuronal populations would be assessed by immunofluorescence and electrophysiology to confirm the identity and functional maturation of interneuron subtypes (e.g., SST+, LAMP5+). A failure of knockout cells to efficiently generate these subtypes compared to controls would support the hypothesis. **Therapeutic Potential:** As a nuclear transcription factor, [ZSCAN21](/details-gene/7589) is a challenging direct therapeutic target. However, its potential status as a tumor-associated antigen, specifically in renal-cell carcinoma, presents a promising avenue for immunotherapy. If its expression is confirmed to be highly specific to tumor cells and absent from most healthy adult somatic tissues (with the exception of immune-privileged germ cells), it could serve as an ideal target. Therapeutic strategies could include the development of T-cell receptor (TCR)-engineered T cells or cancer vaccines designed to elicit a robust immune response against [ZSCAN21](/details-gene/7589)-expressing cancer cells.

Genular Protein ID: 1767313270

Symbol: ZSC21_HUMAN

Name: Zinc finger and SCAN domain-containing protein 21

UniProtKB Accession Codes:

Q9Y5A6 A4D2A6 D6W5T9 Q9H0B5

Database IDs:

ABCD 1 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 1 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 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 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 4 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: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

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: 10508479

Title: Antigens recognized by autologous antibody in patients with renal-cell carcinoma.

PubMed ID: 10508479

DOI: 10.1002/(sici)1097-0215(19991112)83:4&lt;456::aid-ijc4&gt;3.0.co;2-5

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: 473
  • Mass: 53658
  • Checksum: D9A26694B114B96F
  • Sequence:
    • MMTKVLGMAP VLGPRPPQEQ VGPLMVKVEE KEEKGKYLPS LEMFRQRFRQ FGYHDTPGPR 
EALSQLRVLC CEWLRPEIHT KEQILELLVL EQFLTILPQE LQAWVQEHCP ESAEEAVTLL 
EDLERELDEP GHQVSTPPNE QKPVWEKISS SGTAKESPSS MQPQPLETSH KYESWGPLYI 
QESGEEQEFA QDPRKVRDCR LSTQHEESAD EQKGSEAEGL KGDIISVIIA NKPEASLERQ 
CVNLENEKGT KPPLQEAGSK KGRESVPTKP TPGERRYICA ECGKAFSNSS NLTKHRRTHT 
GEKPYVCTKC GKAFSHSSNL TLHYRTHLVD RPYDCKCGKA FGQSSDLLKH QRMHTEEAPY 
QCKDCGKAFS GKGSLIRHYR IHTGEKPYQC NECGKSFSQH AGLSSHQRLH TGEKPYKCKE 
CGKAFNHSSN FNKHHRIHTG EKPYWCHHCG KTFCSKSNLS KHQRVHTGEG EAP