Details for: DSN1

Gene ID: 79980

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: DSN1

Ensembl ID: ENSG00000149636

Description: DSN1 component of MIS12 kinetochore complex

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • fibroblast of lung CL0002553
    CSI 4.25
    rCSI 3.96%
    PRS 98.6
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.97
    rCSI 2.77%
    PRS 98.78
  • neural crest cell CL0011012
    CSI 3.8
    rCSI 3.01%
    PRS 95.83
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.41
    rCSI 2.95%
    PRS 98.48
  • retinal rod cell CL0000604
    CSI 3.38
    rCSI 5.96%
    PRS 95.33
  • common myeloid progenitor CL0000049
    CSI 3.34
    rCSI 2.7%
    PRS 98.57
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.64
    rCSI 3.39%
    PRS 96.31
  • promyelocyte CL0000836
    CSI 2.59
    rCSI 3.74%
    PRS 98.05
  • transit amplifying cell of colon CL0009011
    CSI 2.51
    rCSI 2.95%
    PRS 97.98
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.43
    rCSI 2.81%
    PRS 94.35
  • radial glial cell CL0000681
    CSI 2.23
    rCSI 3.09%
    PRS 97.47
  • mesenchymal cell CL0008019
    CSI 2.11
    rCSI 5.35%
    PRS 96.4
  • glioblast CL0000030
    CSI 2.03
    rCSI 3.23%
    PRS 94.56
  • placental villous trophoblast CL2000060
    CSI 1.97
    rCSI 3.05%
    PRS 96.82
  • retinal cone cell CL0000573
    CSI 1.66
    rCSI 2.68%
    PRS 93.89
  • large pre-B-II cell CL0000957
    CSI 1.66
    rCSI 4.74%
    PRS 96.98
  • primitive red blood cell CL0002355
    CSI 0.97
    rCSI 5.23%
    PRS 97.85
  • erythroid progenitor cell CL0000038
    CSI 0.67
    rCSI 3.82%
    PRS 98.19

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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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 [DSN1](/details-gene/79980), or DSN1 component of MIS12 kinetochore complex, is a protein-coding gene located on chromosome 20q11.23. It encodes a critical component of the MIS12 kinetochore complex, which is essential for the proper attachment of spindle microtubules to chromosomes during cell division [Link](https://doi.org/10.1038/ncb1187). Its primary function is central to maintaining genomic stability by ensuring accurate chromosome segregation during mitosis. Consistent with this fundamental role, expression analysis reveals that [DSN1](/details-gene/79980) is a significant marker for highly proliferative cells across a wide array of lineages. These include structural cells such as [fibroblast of lung](/details-cell/CL0002553), progenitor cells of the immune system like [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557), and developmental precursors including [neural crest cell](/details-cell/CL0011012). ## Cellular Roles and Expression Landscape The expression pattern of [DSN1](/details-gene/79980) is not restricted to a specific cell lineage but is instead a strong indicator of a cell's proliferative state. The **Overall** analysis shows its high significance in diverse cell populations that share a common feature of rapid division or high proliferative potential. * **Mesenchymal and Structural Proliferation:** The gene shows the highest significance in [fibroblast of lung](/details-cell/CL0002553) (CSI: 4.25), a cell type known for its role in tissue repair and extracellular matrix production, which involves active proliferation. Its prominence is also noted in other cells of mesenchymal origin, such as [mesenchymal cell](/details-cell/CL0008019). * **Hematopoietic and Immune Progenitors:** [DSN1](/details-gene/79980) is highly significant in several immune progenitor cells, including [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 3.97), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 3.41), and [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.34). This suggests its critical role during the rapid cell divisions required for hematopoiesis. * **Neural Development and Neoplasia:** The gene is prominently expressed in various neural progenitors, such as [neural crest cell](/details-cell/CL0011012) (CSI: 3.80), [neuroblast (sensu Vertebrata)](/details-cell/CL0000031), and [radial glial cell](/details-cell/CL0000681). Notably, it is also significant in [glioblast](/details-cell/CL0000030), a malignant brain tumor cell type, underscoring its association with uncontrolled cell division in cancer. * **Epithelial Tissue Renewal:** Its high score in [transit amplifying cell of colon](/details-cell/CL0009011) highlights its importance in the constant renewal of epithelial tissues like the intestinal lining. Collectively, the widespread expression of [DSN1](/details-gene/79980) in these varied, actively dividing cell populations confirms its fundamental and universal role in the machinery of cell proliferation. ## Pathways and Molecular Function Functionally, [DSN1](/details-gene/79980) is integral to the process of mitosis. As a core member of the MIS12 complex, it localizes to the [kinetochore](/details-cell/GO:0000776), specifically the [outer kinetochore](/details-cell/GO:0000940), where it facilitates the stable connection between chromosomes and the spindle apparatus [Link](https://doi.org/10.1083/jcb.200509158). This role is critical for the biological process of [Attachment of spindle microtubules to kinetochore](/details-cell/GO:0008608), which is a prerequisite for proper chromosome alignment and segregation. Reactome pathway analysis further corroborates its central role in [Cell cycle, mitotic](/details-cell/R-HSA-69278). [DSN1](/details-gene/79980) is involved in multiple checkpoints and phases of mitosis, including the [Mitotic spindle checkpoint](/details-cell/R-HSA-69618), [Mitotic prometaphase](/details-cell/R-HSA-68877), and the [Separation of sister chromatids](/details-cell/R-HSA-2467813). Interestingly, beyond its canonical cell cycle functions, [DSN1](/details-gene/79980) is also annotated in the [Innate immune system](/details-cell/R-HSA-168249) and [Neutrophil degranulation](/details-cell/R-HSA-6798695) pathways. This, along with its cellular component annotation in the [azurophil granule lumen](/details-cell/GO:0035578), may suggest a secondary or context-specific role in the development or function of immune cells, particularly neutrophils. ## Research Directions The essential and universal function of [DSN1](/details-gene/79980) in cell division makes it a compelling subject for research, particularly in the context of diseases characterized by aberrant proliferation, such as cancer. Its high significance score in [glioblast](/details-cell/CL0000030) cells points directly to its potential involvement in tumorigenesis. Based on the available data, several testable hypotheses can be proposed: 1. Given its indispensable role in the mitotic checkpoint, targeted inhibition of [DSN1](/details-gene/79980) function or expression in rapidly dividing cancer cells, such as glioblastoma, will lead to mitotic failure, aneuploidy, and subsequent cell death, positioning it as a potential therapeutic target. 2. The unexpected association of [DSN1](/details-gene/79980) with [Neutrophil degranulation](/details-cell/R-HSA-6798695) suggests it may have a moonlighting function in terminally differentiated neutrophils or that its regulation is uniquely coupled to effector functions during myelopoiesis, linking the cell cycle machinery to innate immune processes. A key experiment to test the first hypothesis could be designed as follows: * To evaluate the role of [DSN1](/details-gene/79980) as a therapeutic target in glioblastoma, a CRISPR interference (CRISPRi) system could be employed to achieve inducible knockdown of [DSN1](/details-gene/79980) in patient-derived [glioblast](/details-cell/CL0000030) cell lines. The effects of its depletion could be assessed by quantifying cell viability over time, analyzing cell cycle distribution via flow cytometry, and monitoring for markers of mitotic catastrophe and apoptosis using immunofluorescence and western blotting. **Therapeutic Potential:** As a crucial factor for cell proliferation, [DSN1](/details-gene/79980) represents an attractive target for anti-cancer therapies. The therapeutic strategy would focus on **inhibition**. However, because [DSN1](/details-gene/79980) is also essential for healthy, proliferating tissues (e.g., in the hematopoietic system and gut epithelium), systemic inhibitors would likely have high toxicity. Therefore, the development of targeted delivery systems, such as antibody-drug conjugates or lipid nanoparticles carrying siRNAs or small molecule inhibitors, would be critical to direct the therapeutic agent specifically to tumor cells and improve the therapeutic window.

Genular Protein ID: 2600520432

Symbol: DSN1_HUMAN

Name: Kinetochore-associated protein DSN1 homolog

UniProtKB Accession Codes:

Q9H410 B4DWT2 E1P5U9 Q5JW55 Q5JW56 Q9H8P4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 EMDB 3 Ensembl 4 ExpressionAtlas 1 GO 15 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 7 RefSeq 6 SIGNOR 1 SMR 1 STRING 1 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: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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: 15502821

Title: A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1.

PubMed ID: 15502821

DOI: 10.1038/ncb1187

PubMed ID: 16585270

Title: The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation.

PubMed ID: 16585270

DOI: 10.1083/jcb.200509158

PubMed ID: 17981135

Title: Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1.

PubMed ID: 17981135

DOI: 10.1016/j.devcel.2007.09.005

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

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

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23035123

Title: Mitotic regulator SKAP forms a link between kinetochore core complex KMN and dynamic spindle microtubules.

PubMed ID: 23035123

DOI: 10.1074/jbc.m112.406652

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 356
  • Mass: 40067
  • Checksum: C75E113BE2A82A8B
  • Sequence:
    • MTSVTRSEII DEKGPVMSKT HDHQLESSLS PVEVFAKTSA SLEMNQGVSE ERIHLGSSPK 
KGGNCDLSHQ ERLQSKSLHL SPQEQSASYQ DRRQSWRRAS MKETNRRKSL HPIHQGITEL 
SRSISVDLAE SKRLGCLLLS SFQFSIQKLE PFLRDTKGFS LESFRAKASS LSEELKHFAD 
GLETDGTLQK CFEDSNGKAS DFSLEASVAE MKEYITKFSL ERQTWDQLLL HYQQEAKEIL 
SRGSTEAKIT EVKVEPMTYL GSSQNEVLNT KPDYQKILQN QSKVFDCMEL VMDELQGSVK 
QLQAFMDEST QCFQKVSVQL GKRSMQQLDP SPARKLLKLQ LQNPPAIHGS GSGSCQ

Genular Protein ID: 1355998632

Symbol: A8K3X3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K3X3

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 1 SAM 1

Sequence Information:

  • Length: 356
  • Mass: 40093
  • Checksum: 50F94C06DF75FB43
  • Sequence:
    • MTPVTRSEII DEKGPVMSKT HDHQLESSLS PVEVFAKTSA SLEMNQGVSE ERIHLGSSPK 
KGGNCDLSHQ ERLQSKSLHL SPQEQSASYQ DRRQSWRRSS MKETNRRKSL HPIHQGITEL 
SRSISVDLAE SKRLGCLLLS SFQFSIQKLE PFLRDTKGFS LESFRAKASS LSEELKHFAD 
GLETDGTLQK CFEDSNGKAS DFSLEASVAE MKEYITKFSL ERQTWDQLLL HYQQEAKEIL 
SRGSTEAKIT EVKVEPMTYL GSSQNEVLNT KPDYQKILQN QSKVFDCMEL VMDELQGSVK 
QLQAFMDEST QCFQKVSVQL GKRSMQQLDP SPARKLLKLQ LQNPPAIHGS GSGSCQ