Details for: ZKSCAN8

Gene ID: 7745

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: ZKSCAN8

Ensembl ID: ENSG00000198315

Description: zinc finger with KRAB and SCAN domains 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mucosal invariant T cell CL0000940
    CSI 4.73
    rCSI 3.82%
    PRS 98.35
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.44
    rCSI 3.1%
    PRS 95.98
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.98
    rCSI 3.71%
    PRS 88.1
  • group 3 innate lymphoid cell CL0001071
    CSI 2.71
    rCSI 2.04%
    PRS 97.6
  • vascular leptomeningeal cell CL4023051
    CSI 2.66
    rCSI 4.66%
    PRS 94.65
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.62
    rCSI 3.13%
    PRS 89.73
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.57
    rCSI 1.98%
    PRS 98.09
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.38
    rCSI 5.34%
    PRS 89.99
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.12
    rCSI 2.74%
    PRS 90.48
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.93
    rCSI 3.42%
    PRS 89.33
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.83
    rCSI 3.08%
    PRS 89.77
  • cardiac muscle cell CL0000746
    CSI 1.46
    rCSI 2.1%
    PRS 91.46

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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Comma-separated if multiple.
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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 [ZKSCAN8](/details-gene/7745) (Zinc finger with KRAB and SCAN domains 8) is a protein-coding gene located on chromosome 6p22.1. Functionally, it is characterized as a DNA-binding transcription factor that specifically regulates gene expression via RNA polymerase II. Its protein structure includes a SCAN box and a KRAB domain, which are typically involved in protein-protein interactions and transcriptional repression, respectively ([Link](https://pubmed.ncbi.nlm.nih.gov/9244436/)). The protein localizes to the '[Nucleus](/details-gene/GO:0005634)', consistent with its role in transcription. **Overall**, expression data reveals that [ZKSCAN8](/details-gene/7745) is a significant gene in a diverse range of cell types, including specialized immune cells such as the '[mucosal invariant T cell](/details-cell/CL0000940)', hematopoietic progenitors like the '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)', and multiple subtypes of cortical interneurons, suggesting a fundamental role in regulating cellular identity across different lineages. ## Cellular Roles and Expression Landscape The expression profile of [ZKSCAN8](/details-gene/7745) highlights its importance in distinct and functionally diverse cellular contexts. **Overall**, the gene shows the highest significance in '[mucosal invariant T cell](/details-cell/CL0000940)' (CSI: 4.73), a unique T cell lineage, and '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' (CSI: 3.44), indicating a potential role in both the innate-like adaptive immune system and hematopoietic development. Furthermore, [ZKSCAN8](/details-gene/7745) is notably prominent in the central nervous system, with high significance scores across multiple GABAergic cortical interneuron subtypes, including '[pvalb GABAergic cortical interneuron](/details-cell/CL4023018)', '[VIP GABAergic cortical interneuron](/details-cell/CL4023016)', '[sst GABAergic cortical interneuron](/details-cell/CL4023017)', and '[lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)'. This widespread yet specific expression pattern within neuronal subsets suggests it may contribute to the transcriptional programs that define the identity and function of these inhibitory neurons. The gene's significance extends to other cell types such as '[group 3 innate lymphoid cell](/details-cell/CL0001071)', '[vascular leptomeningeal cell](/details-cell/CL4023051)', and '[cardiac muscle cell](/details-cell/CL0000746)', reinforcing its broad but specific regulatory roles in various tissues. ## Pathways and Molecular Function The functional annotations for [ZKSCAN8](/details-gene/7745) firmly establish it as a key component of the transcriptional machinery. Its primary biological process is the '[Regulation of transcription by rna polymerase ii](/details-gene/GO:0006357)', which is supported by its molecular function as a '[Dna-binding transcription factor activity, rna polymerase ii-specific](/details-gene/GO:0000981)'. This activity is part of the broader Reactome pathways '[Gene expression (transcription)](/details-pathway/R-HSA-74160)' and '[Rna polymerase ii transcription](/details-pathway/R-HSA-73857)'. As a zinc finger protein, its '[Metal ion binding](/details-gene/GO:0046872)' function is integral to its ability to bind DNA at cis-regulatory regions. The annotation for '[Protein binding](/details-gene/GO:0005515)' suggests it likely operates as part of a larger protein complex, a common feature for KRAB and SCAN domain-containing proteins which often recruit co-repressors to modulate gene expression. Furthermore, multiple studies have identified [ZKSCAN8](/details-gene/7745) as a target of post-translational modifications, including phosphorylation and SUMOylation, suggesting its transcriptional activity is dynamically regulated in response to cellular signals like mitosis and DNA damage ([Link](https://doi.org/10.1073/pnas.0805139105), [Link](https://doi.org/10.1038/nsmb.2890)). ## Research Directions The diverse expression pattern of [ZKSCAN8](/details-gene/7745) across seemingly unrelated, highly specialized cell types points to a fundamental yet context-specific regulatory role that warrants further investigation. ### Proposed Hypotheses 1. **Hypothesis 1:** Given its high significance in multiple distinct subtypes of cortical inhibitory neurons ('[pvalb](/details-cell/CL4023018)', '[VIP](/details-cell/CL4023016)', '[sst](/details-cell/CL4023017)'), '[ZKSCAN8](/details-gene/7745)' may function as a master regulator that establishes or maintains the transcriptional identity and functional properties of these specific interneuron classes during neurodevelopment. 2. **Hypothesis 2:** The high significance of '[ZKSCAN8](/details-gene/7745)' in both a hematopoietic progenitor ('[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)') and mature lymphoid cells ('[mucosal invariant T cell](/details-cell/CL0000940)', '[group 3 innate lymphoid cell](/details-cell/CL0001071)') suggests it regulates a core set of genes governing lineage commitment and terminal differentiation shared between these developmental pathways. ### Key Experimental Approach To test Hypothesis 1, the role of '[ZKSCAN8](/details-gene/7745)' in cortical interneuron specification could be investigated using a conditional knockout mouse model. By crossing a floxed '[ZKSCAN8](/details-gene/7745)' allele with a Cre-driver line specific to cortical interneuron progenitors (e.g., *Nkx2-1*-Cre), one could specifically ablate the gene in this lineage. The resulting phenotype could be assessed using a combination of single-cell RNA sequencing (scRNA-seq) on the postnatal cortex to determine if the normal diversity and transcriptional profiles of interneuron subtypes are disrupted, and patch-clamp electrophysiology to measure functional deficits in the affected neurons. ### Therapeutic Potential As an intracellular transcription factor, '[ZKSCAN8](/details-gene/7745)' represents a challenging direct drug target using conventional small molecules or antibodies. Its widespread expression in critical cell types within the immune, hematopoietic, and nervous systems raises a significant risk of off-target effects with systemic therapies. Therefore, its potential as a therapeutic target is likely limited. However, if future research links mutations or dysregulation of '[ZKSCAN8](/details-gene/7745)' to specific pathologies, such as neurodevelopmental disorders or hematological malignancies, it could serve as a valuable diagnostic biomarker. In such specific contexts, therapeutic strategies might involve indirect modulation of its downstream targets or advanced gene-level interventions rather than direct inhibition of the protein itself.

Genular Protein ID: 4106941190

Symbol: ZKSC8_HUMAN

Name: Zinc finger protein with KRAB and SCAN domains 8

UniProtKB Accession Codes:

Q15776 A1L3D4 B4DYF1 Q4VAR1 Q4VAR2 Q4VAR3 Q9H4T1

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 4 ExpressionAtlas 1 GO 5 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 5 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9244436

Title: Three genes encoding zinc finger proteins on human chromosome 6p21.3: members of a new subclass of the Kruppel gene family containing the conserved SCAN box domain.

PubMed ID: 9244436

DOI: 10.1006/geno.1997.4806

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 8673473

Title: A strategy for cloning the hereditary hemochromatosis gene.

PubMed ID: 8673473

DOI: 10.1006/bcmd.1995.0024

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 25218447

Title: Uncovering global SUMOylation signaling networks in a site-specific manner.

PubMed ID: 25218447

DOI: 10.1038/nsmb.2890

PubMed ID: 25772364

Title: SUMO-2 orchestrates chromatin modifiers in response to DNA damage.

PubMed ID: 25772364

DOI: 10.1016/j.celrep.2015.02.033

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: 578
  • Mass: 65816
  • Checksum: 0A4FCA610DFF31F2
  • Sequence:
    • MAEESRKPSA PSPPDQTPEE DLVIVKVEED HGWDQESSLH ESNPLGQEVF RLRFRQLRYQ 
ETLGPREALI QLRALCHQWL RPDLNTKEQI LELLVLEQFL TILPEELQTL VKEHQLENGE 
EVVTLLEDLE RQIDILGRPV SARVHGHRVL WEEVVHSASA PEPPNTQLQS EATQHKSPVP 
QESQERAMST SQSPTRSQKG SSGDQEMTAT LLTAGFQTLE KIEDMAVSLI REEWLLDPSQ 
KDLCRDNRPE NFRNMFSLGG ETRSENRELA SKQVISTGIQ PHGETAAKCN GDVIRGLEHE 
EARDLLGRLE RQRGNPTQER RHKCDECGKS FAQSSGLVRH WRIHTGEKPY QCNVCGKAFS 
YRSALLSHQD IHNKVKRYHC KECGKAFSQN TGLILHQRIH TGEKPYQCNQ CGKAFSQSAG 
LILHQRIHSG ERPYECNECG KAFSHSSHLI GHQRIHTGEK PYECDECGKT FRRSSHLIGH 
QRSHTGEKPY KCNECGRAFS QKSGLIEHQR IHTGERPYKC KECGKAFNGN TGLIQHLRIH 
TGEKPYQCNE CGKAFIQRSS LIRHQRIHSG EKSESISV

Genular Protein ID: 2722665497

Symbol: Q59HG5_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q59HG5

Database IDs:

ARBA 7 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 2 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 5 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 2 RefSeq 3 SAM 1 SMART 2 SUPFAM 2

Sequence Information:

  • Length: 441
  • Mass: 49855
  • Checksum: C24F731DA64C2D71
  • Sequence:
    • KEVSARVHGH RVLWEEVVHS ASAPEPPNTQ LQSEATQHKS PVPQESQERA MSTSQSPTRS 
QKGSSGDQEM TATLLTAGFQ TLEKIEDMAV SLIREEWLLD PSQKDLCRDN RPENFRNMFS 
LGGETRSENR ELASKQVIST GIQPHGETAA KCNGDVIRGL EHEEARDLLG RLERQRGNPT 
QERRHKCDEC GKSFAQSSGL VRHWRIHTGE KPYQCNVCGK AFSYRSALLS HQDIHNKVKR 
YHCKECGKAF SQNTGLILHQ RIHTGEKPYQ CNQCGKAFSQ SAGLILHQRI HSGERPYECN 
ECGKAFSHSS HLIGHQRIHT GEKPYECDEC GKTFRRSSHL IGHQRSHTGE KPYKCNECGR 
AFSQKSGLIE HQRIHTGERP YKCKECGKAF NGNTGLIQHL RIHTGEKPYQ CNECGKAFIQ 
RSSLIRHQRI HSGEKSESIS V