Details for: MIS12

Gene ID: 79003

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: MIS12

Ensembl ID: ENSG00000167842

Description: MIS12 kinetochore complex component

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 5.19
    rCSI 4.16%
    PRS 95.62
  • pro-B cell CL0000826
    CSI 3.92
    rCSI 3.24%
    PRS 94.01
  • unswitched memory B cell CL0000970
    CSI 3.63
    rCSI 3.05%
    PRS 97.99
  • naive T cell CL0000898
    CSI 3.28
    rCSI 2.28%
    PRS 98.6
  • CD4-positive helper T cell CL0000492
    CSI 3.26
    rCSI 2.47%
    PRS 98.19
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.15
    rCSI 2.2%
    PRS 95.69
  • mature B cell CL0000785
    CSI 3.06
    rCSI 2.66%
    PRS 97.31
  • T follicular helper cell CL0002038
    CSI 3.05
    rCSI 2.28%
    PRS 98.18
  • perivascular cell CL4033054
    CSI 3
    rCSI 4.1%
    PRS 95.61
  • small pre-B-II cell CL0000954
    CSI 2.97
    rCSI 2.86%
    PRS 97.57
  • neural crest cell CL0011012
    CSI 2.85
    rCSI 2.25%
    PRS 87.81
  • rod bipolar cell CL0000751
    CSI 2.83
    rCSI 5.09%
    PRS 89.21
  • group 3 innate lymphoid cell CL0001071
    CSI 2.68
    rCSI 2.02%
    PRS 95.33
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.47
    rCSI 2.51%
    PRS 96.75
  • retina horizontal cell CL0000745
    CSI 2.4
    rCSI 3.65%
    PRS 90.58
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.38
    rCSI 2.75%
    PRS 86.81
  • intestine goblet cell CL0019031
    CSI 2.3
    rCSI 2.04%
    PRS 91.27
  • lung ciliated cell CL1000271
    CSI 2.25
    rCSI 2.61%
    PRS 88.88
  • retinal bipolar neuron CL0000748
    CSI 2.2
    rCSI 4.12%
    PRS 86.57
  • ciliated epithelial cell CL0000067
    CSI 2.11
    rCSI 1.85%
    PRS 85.99
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.08
    rCSI 4.65%
    PRS 83.42
  • retinal rod cell CL0000604
    CSI 1.96
    rCSI 3.45%
    PRS 89.82
  • peripheral nervous system neuron CL2000032
    CSI 1.87
    rCSI 2.55%
    PRS 87.78
  • radial glial cell CL0000681
    CSI 1.84
    rCSI 2.55%
    PRS 91.83
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.84
    rCSI 1.66%
    PRS 92.33
  • mesenchymal cell CL0008019
    CSI 1.74
    rCSI 4.43%
    PRS 89.3
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.71
    rCSI 3.03%
    PRS 82.45
  • glioblast CL0000030
    CSI 1.59
    rCSI 2.54%
    PRS 87.04
  • basal cell CL0000646
    CSI 1.57
    rCSI 2.1%
    PRS 90.85
  • type B pancreatic cell CL0000169
    CSI 1.53
    rCSI 3.4%
    PRS 93.08
  • retinal cone cell CL0000573
    CSI 1.42
    rCSI 2.28%
    PRS 86.7
  • podocyte CL0000653
    CSI 0.84
    rCSI 3.75%
    PRS 93.43

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 Analyzed for its expression specificity (CSI Z-SCORE), [MIS12](/gene/79003) is identified not as a cell type-specific marker but as a ubiquitously expressed gene essential for a fundamental biological process. Its expression pattern is consistent with its well-established role as a core component of the kinetochore, which is required for chromosome segregation during mitosis in all proliferating cells. ## Cellular Roles and Expression Landscape The expression profile of [MIS12](/gene/79003), when evaluated for specificity, highlights its role as a housekeeping gene involved in cell division rather than a marker of cellular identity. In the **Overall** context, the gene displays a CSI (Z-SCORE) of approximately 0.00 across a wide array of cell types, including hematopoietic progenitors like [pro-B cell](/details-cell/CL0000826) and developing lymphocytes such as [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810) and [double-positive, alpha-beta thymocyte](/details-cell/CL0000809). This score, combined with high non-significant p-values (e.g., p > 0.6), indicates that the expression of [MIS12](/gene/79003) is not statistically enriched in any single cell type relative to others. Instead, its presence in diverse and often highly proliferative lineages—ranging from immune cells ([unswitched memory B cell](/details-cell/CL0000970), [naive T cell](/details-cell/CL0000898)) to non-hematopoietic cells like [perivascular cell](/details-cell/CL4033054) and [retina horizontal cell](/details-cell/CL0000745)—suggests that its expression is primarily dictated by the cell's proliferative state rather than its specific function or lineage. This is strongly supported by its essential function in mitosis, as documented in several studies (PubMed: [12515822](https://pubmed.ncbi.nlm.nih.gov/12515822/), [16585270](https://pubmed.ncbi.nlm.nih.gov/16585270/)). ## Pathways and Molecular Function The functional annotations for [MIS12](/gene/79003) align perfectly with its broad expression pattern in dividing cells. As a core component of the Mis12/MIND complex ([GO:0000444](https://www.ebi.ac.uk/QuickGO/term/GO:0000444)), it is localized to the kinetochore ([GO:0000776](https://www.ebi.ac.uk/QuickGO/term/GO:0000776)) and plays a critical, conserved role in cell division. Seminal research has demonstrated that the human Mis12 complex is indispensable for kinetochore assembly and the proper segregation of chromosomes (PubMed: [16585270](https://pubmed.ncbi.nlm.nih.gov/16585270/)). Its involvement is central to numerous Reactome pathways governing cell cycle progression, including '[Cell cycle, mitotic](/details-pathway/R-HSA-69278)', '[M phase](/details-pathway/R-HSA-68886)', and '[Mitotic spindle checkpoint](/details-pathway/R-HSA-69618)'. Specifically, [MIS12](/gene/79003) is integral to the '[Attachment of mitotic spindle microtubules to kinetochore](/details-go/GO:0051315)', a process that ensures genomic stability during cell division. Research by Goshima et al. established its essential role in equal chromosome segregation (DOI: [10.1083/jcb.200210005](https://doi.org/10.1083/jcb.200210005)). This function explains why its transcript is required in any cell population undergoing proliferation, from thymic development to B cell memory formation. ## Research Directions Given that [MIS12](/gene/79003) expression levels are a proxy for mitotic activity rather than cell identity, future research should focus on the regulation of its function and its potential as a biomarker or therapeutic target in diseases of uncontrolled proliferation. ### Testable Hypotheses 1. **Hypothesis:** Post-translational modifications (PTMs), rather than transcript abundance, are the primary mechanism regulating [MIS12](/gene/79003) function during the immune response. Specifically, phosphorylation of MIS12 may be significantly different between rapidly expanding effector T cells and quiescent naive T cells, despite similar mRNA levels. * **Experiment:** Perform immunoprecipitation of MIS12 from synchronized populations of activated and naive T cells, followed by quantitative mass spectrometry (phosphoproteomics) to identify and compare phosphorylation sites and their stoichiometry. 2. **Hypothesis:** While broadly expressed, subtle variations in the stoichiometry of the Mis12/MIND complex components may exist across different lineages, leading to differential fidelity of chromosome segregation. For example, hematopoietic stem and progenitor cells may have a more robustly assembled complex compared to terminally differentiated cells re-entering the cell cycle. * **Experiment:** Use proximity-ligation assays (PLA) or co-immunoprecipitation followed by Western blot to quantify the interaction strength between [MIS12](/gene/79003) and its core partners (e.g., DSN1, NSL1, PMF1) in isolated hematopoietic stem cells versus mature B cells induced to proliferate in vitro. 3. **Hypothesis:** The ubiquitous expression of [MIS12](/gene/79003) makes it a dependency in aneuploid cancer cells, which experience high levels of mitotic stress. Therefore, partial inhibition of [MIS12](/gene/79003) function will be selectively lethal to cancer cells while being tolerated by healthy proliferating cells. * **Experiment:** Develop or utilize a small molecule inhibitor targeting [MIS12](/gene/79003) or its interactions. Treat a panel of cancer cell lines with varying degrees of aneuploidy alongside healthy, proliferating primary cells (e.g., activated T cells, intestinal organoids) and measure the differential impact on mitotic catastrophe, apoptosis, and overall viability. ### Therapeutic Potential The essential and universal role of [MIS12](/gene/79003) in cell division makes it a compelling, albeit challenging, target for anti-cancer therapies. Its function is critical for the survival of rapidly proliferating tumor cells. The primary challenge lies in achieving a therapeutic window that distinguishes cancer cells from healthy, rapidly dividing tissues such as the gut epithelium and hematopoietic progenitors. Strategies could involve developing inhibitors that target cancer-specific PTMs on MIS12 or exploiting synthetic lethality by combining a MIS12-targeting agent with drugs that inhibit other cell cycle checkpoint proteins frequently mutated in cancers.

Genular Protein ID: 3149670301

Symbol: MIS12_HUMAN

Name: Protein MIS12 homolog

UniProtKB Accession Codes:

Q9H081 Q96N24

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 EMDB 3 Ensembl 3 ExpressionAtlas 1 GO 12 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 6 RefSeq 9 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TopDownProteomics 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: 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: 12515822

Title: Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway.

PubMed ID: 12515822

DOI: 10.1083/jcb.200210005

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23891108

Title: Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK.

PubMed ID: 23891108

DOI: 10.1016/j.cub.2013.06.040

Sequence Information:

  • Length: 205
  • Mass: 24140
  • Checksum: 8CC906E843D4BD56
  • Sequence:
    • MSVDPMTYEA QFFGFTPQTC MLRIYIAFQD YLFEVMQAVE QVILKKLDGI PDCDISPVQI 
RKCTEKFLCF MKGHFDNLFS KMEQLFLQLI LRIPSNILLP EDKCKETPYS EEDFQHLQKE 
IEQLQEKYKT ELCTKQALLA ELEEQKIVQA KLKQTLTFFD ELHNVGRDHG TSDFRESLVS 
LVQNSRKLQN IRDNVEKESK RLKIS

Genular Protein ID: 201810472

Symbol: A8K1M4_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K1M4

Database IDs:

ARBA 8 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMR 1

Sequence Information:

  • Length: 205
  • Mass: 24110
  • Checksum: 8CD51B2983D4BD56
  • Sequence:
    • MSVDPMTYEA QFFGFTPQTC MLRIYIAFQD YLFEVMQAVE QVILKKLDGI PDCDISPVQI 
RKCTEKFLCF MKGHFDNLFS KMEQLFLQLI LRIPSNILLP EDKCKETPYS EEDFQHLQKE 
IEQLQEKYKT ELCTKQALLA ELEEQKIVQA KLKQTLTFFD ELHNVGRDHG TGDFRESLVS 
LVQNSRKLQN IRDNVEKESK RLKIS