Details for: MIS18A

Gene ID: 54069

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: MIS18A

Ensembl ID: ENSG00000159055

Description: MIS18 kinetochore protein A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pro-B cell CL0000826
    CSI 4.27
    rCSI 3.54%
    PRS 96.37
  • interneuron CL0000099
    CSI 3.75
    rCSI 7.52%
    PRS 92.41
  • neural crest cell CL0011012
    CSI 3.32
    rCSI 2.62%
    PRS 92
  • transit amplifying cell of colon CL0009011
    CSI 3.31
    rCSI 3.88%
    PRS 95.79
  • rod bipolar cell CL0000751
    CSI 3.09
    rCSI 5.55%
    PRS 92.24
  • placental villous trophoblast CL2000060
    CSI 3.04
    rCSI 4.7%
    PRS 94.29
  • stem cell CL0000034
    CSI 2.89
    rCSI 2.78%
    PRS 93.56
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.83
    rCSI 2.45%
    PRS 96.69
  • intestine goblet cell CL0019031
    CSI 2.78
    rCSI 2.47%
    PRS 94.07
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.77
    rCSI 2.51%
    PRS 94.98
  • ciliated epithelial cell CL0000067
    CSI 2.74
    rCSI 2.41%
    PRS 89.73
  • intestinal epithelial cell CL0002563
    CSI 2.6
    rCSI 2.72%
    PRS 94.03
  • mesodermal cell CL0000222
    CSI 2.56
    rCSI 3.08%
    PRS 95.43
  • OFF-bipolar cell CL0000750
    CSI 2.52
    rCSI 3.45%
    PRS 93.89
  • hematopoietic stem cell CL0000037
    CSI 2.48
    rCSI 1.65%
    PRS 96.36
  • common myeloid progenitor CL0000049
    CSI 2.41
    rCSI 1.95%
    PRS 96.43
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.38
    rCSI 2.75%
    PRS 90.38
  • retina horizontal cell CL0000745
    CSI 2.38
    rCSI 3.62%
    PRS 93.59
  • multi-ciliated epithelial cell CL0005012
    CSI 2.34
    rCSI 2.33%
    PRS 91.73
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.33
    rCSI 6.88%
    PRS 95.35
  • promyelocyte CL0000836
    CSI 2.33
    rCSI 3.35%
    PRS 96.32
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.32
    rCSI 2.97%
    PRS 93.05
  • radial glial cell CL0000681
    CSI 2.32
    rCSI 3.22%
    PRS 94.57
  • respiratory hillock cell CL4030023
    CSI 2.27
    rCSI 4.05%
    PRS 97.06
  • peripheral nervous system neuron CL2000032
    CSI 2.23
    rCSI 3.04%
    PRS 91.63
  • common dendritic progenitor CL0001029
    CSI 2.02
    rCSI 2.53%
    PRS 97.8
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.98
    rCSI 3.49%
    PRS 87.65
  • club cell CL0000158
    CSI 1.95
    rCSI 2.86%
    PRS 93.13
  • glioblast CL0000030
    CSI 1.92
    rCSI 3.07%
    PRS 90.53
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.8
    rCSI 2.32%
    PRS 88.98
  • mesenchymal cell CL0008019
    CSI 1.63
    rCSI 4.13%
    PRS 93.15
  • erythroid progenitor cell CL0000038
    CSI 1.44
    rCSI 8.27%
    PRS 96.53
  • large pre-B-II cell CL0000957
    CSI 1.22
    rCSI 3.47%
    PRS 94.68
  • transit amplifying cell of small intestine CL0009012
    CSI 0.95
    rCSI 4.17%
    PRS 96.82
  • primitive red blood cell CL0002355
    CSI 0.94
    rCSI 5.09%
    PRS 95.9
  • pluripotent stem cell CL0002248
    CSI 0.32
    rCSI 9.66%
    PRS 97.66

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

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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 [MIS18A](/details-gene/54069) (MIS18 kinetochore protein A) is a protein-coding gene located on chromosome 21q22.11. It encodes the Mis18-alpha protein, a critical component of the kinetochore-associated machinery essential for proper chromosome segregation during mitosis. The primary function of [MIS18A](/details-gene/54069) is to prime the centromere for the deposition of the centromere-specific histone H3 variant, CENP-A, a foundational step for kinetochore assembly. Its expression profile reflects this role, showing high significance in a wide array of highly proliferative cell types, including hematopoietic progenitors such as [pro-B cell](/details-cell/CL0000826), neural progenitors, and various tissue-specific stem and transit-amplifying cells. ## Cellular Roles and Expression Landscape The expression pattern of [MIS18A](/details-gene/54069) is strongly indicative of its fundamental role in cell division and proliferation. **Overall**, the gene exhibits high significance in numerous populations of progenitor and stem cells across different lineages, underscoring its conserved function in maintaining genomic integrity during cell renewal. Key cell types where [MIS18A](/details-gene/54069) shows high significance include: * **Hematopoietic System:** The gene is a prominent marker in hematopoietic progenitors, including [pro-B cell](/details-cell/CL0000826) (CSI: 4.27), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.83), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.77), and [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 2.48). This is consistent with the high mitotic activity required for hematopoiesis. * **Neural and Progenitor Cells:** High significance is observed in [interneuron](/details-cell/CL0000099) (CSI: 3.75), [neural crest cell](/details-cell/CL0011012) (CSI: 3.32), and retinal cells like [rod bipolar cell](/details-cell/CL0000751) (CSI: 3.09). While some of these are post-mitotic, high expression may reflect developmental origins or potentially a role in chromatin maintenance. * **Epithelial and Tissue-Specific Progenitors:** The gene is also highly significant in cells responsible for tissue turnover and development, such as [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 3.31), [placental villous trophoblast](/details-cell/CL2000060) (CSI: 3.04), and [intestine goblet cell](/details-cell/CL0019031) (CSI: 2.78). The broad but specific expression in these diverse, actively dividing cell populations confirms that [MIS18A](/details-gene/54069) is a core component of the machinery governing cell proliferation. ## Pathways and Molecular Function Functionally, [MIS18A](/details-gene/54069) is integral to the maintenance of chromosome stability. It operates as part of the CENP-A recruiting complex, which is essential for the proper assembly of the centromere. Research has shown that Mis18-alpha, in concert with Mis18-beta and M18BP1, is required for priming the centromere for the recruitment of CENP-A during the G1 phase of the cell cycle ([Link](https://doi.org/10.1016/j.devcel.2006.11.002)). This role is reflected in its associated biological processes and pathways: * **Biological Process (GO):** The gene is annotated with functions central to mitosis, including [Cell division](/details-cell/GO:0051301), [Cenp-a containing chromatin assembly](/details-cell/GO:0034080), and [Chromosome segregation](/details-cell/GO:0007059). It is also involved in [Protein localization to chromosome, centromeric region](/details-cell/GO:0071459). * **Molecular Function (GO):** It exhibits [Protein binding](/details-cell/GO:0005515) and [Protein-macromolecule adaptor activity](/details-cell/GO:0030674), which are necessary for its role in assembling the multi-protein complex at the centromere. * **Cellular Component (GO):** [MIS18A](/details-gene/54069) localizes to the [Chromosome, centromeric region](/details-cell/GO:0000775) and is a component of the [Cenp-a recruiting complex](/details-cell/GO:0098654) within the [Nucleus](/details-cell/GO:0005634). * **Reactome Pathways:** Its function is situated within the broader context of the [Cell cycle](/details-cell/R-HSA-1640170), specifically in [Chromosome maintenance](/details-cell/R-HSA-73886) and the [Deposition of new cenpa-containing nucleosomes at the centromere](/details-cell/R-HSA-606279). ## Research Directions Given the essential role of [MIS18A](/details-gene/54069) in centromere function and cell division, future research should focus on its potential role in disease, particularly in cancers characterized by chromosomal instability. **Proposed Hypotheses:** 1. **Hypothesis 1: Role in Oncogenesis via Aneuploidy.** Dysregulation of [MIS18A](/details-gene/54069) expression or function in rapidly dividing cells, such as [transit amplifying cell of colon](/details-cell/CL0009011) or hematopoietic progenitors, leads to errors in CENP-A deposition. This would result in defective kinetochore formation, chromosome mis-segregation, and aneuploidy, thereby promoting tumorigenesis. 2. **Hypothesis 2: Non-Mitotic Functions in Post-Mitotic Cells.** The high significance of [MIS18A](/details-gene/54069) in terminally differentiated cells like [interneuron](/details-cell/CL0000099) suggests a potential non-canonical, non-mitotic role. In these cells, [MIS18A](/details-gene/54069) may contribute to the long-term maintenance of centromeric chromatin structure and heterochromatin organization, which is crucial for preserving genomic stability over the lifespan of the cell. **Proposed Key Experiment:** To test the first hypothesis, one could investigate the consequences of [MIS18A](/details-gene/54069) loss in a relevant cancer model. A suitable experiment would involve using CRISPR-Cas9 to knock out [MIS18A](/details-gene/54069) in a colorectal cancer cell line. The resulting cellular phenotype could be assessed by quantifying rates of mitotic errors (e.g., lagging chromosomes, anaphase bridges) using live-cell imaging of fluorescently labeled histones and tubulin. Furthermore, the downstream consequence of aneuploidy could be measured directly via karyotyping or single-cell whole-genome sequencing to determine if [MIS18A](/details-gene/54069) depletion induces specific patterns of chromosomal gains or losses. **Therapeutic Potential:** As a critical regulator of cell division, [MIS18A](/details-gene/54069) presents a potential target for anti-cancer therapeutics. Inhibition of its function would be expected to disrupt kinetochore assembly, leading to mitotic arrest and cell death (mitotic catastrophe) preferentially in highly proliferative cancer cells. However, its essential role in healthy progenitor populations, such as [hematopoietic stem cell](/details-cell/CL0000037), suggests that systemic inhibition could cause severe on-target toxicities, including myelosuppression and gastrointestinal damage. Therefore, therapeutic strategies targeting [MIS18A](/details-gene/54069) would likely require tumor-specific delivery mechanisms, such as encapsulation in nanoparticles or conjugation to a tumor-targeting antibody, to be clinically viable.

Genular Protein ID: 2584201989

Symbol: MS18A_HUMAN

Name: Protein Mis18-alpha

UniProtKB Accession Codes:

Q9NYP9 B2R562 Q542Z0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEBI 4 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 3 Ensembl 1 GO 10 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 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 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10773462

Title: Criteria for gene identification and features of genome organization: analysis of 6.5 Mb of DNA sequence from human chromosome 21.

PubMed ID: 10773462

DOI: 10.1016/s0378-1119(00)00089-5

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

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: 17199038

Title: Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1.

PubMed ID: 17199038

DOI: 10.1016/j.devcel.2006.11.002

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: 26921242

Title: Centromere localization and function of Mis18 requires Yippee-like domain-mediated oligomerization.

PubMed ID: 26921242

DOI: 10.15252/embr.201541520

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: 233
  • Mass: 25863
  • Checksum: A07522806C4B6221
  • Sequence:
    • MAGVRSLRCS RGCAGGCECG DKGKCSDSSL LGKRLSEDSS RHQLLQKWAS MWSSMSEDAS 
VADMERAQLE EEAAAAEERP LVFLCSGCRR PLGDSLSWVA SQEDTNCILL RCVSCNVSVD 
KEQKLSKREK ENGCVLETLC CAGCSLNLGY VYRCTPKNLD YKRDLFCLSV EAIESYVLGS 
SEKQIVSEDK ELFNLESRVE IEKSLTQMED VLKALQMKLW EAESKLSFAT CKS