Details for: CNOT9

Gene ID: 9125

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: CNOT9

Ensembl ID: ENSG00000144580

Description: CCR4-NOT transcription complex subunit 9

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • transit amplifying cell CL0009010
    CSI 13.28
    rCSI 20.31%
    PRS 82.88
  • enteroendocrine cell CL0000164
    CSI 9.18
    rCSI 12.55%
    PRS 72.93
  • type B pancreatic cell CL0000169
    CSI 5
    rCSI 11.07%
    PRS 70.9
  • mature alpha-beta T cell CL0000791
    CSI 4.59
    rCSI 16.62%
    PRS 88.86
  • multi-ciliated epithelial cell CL0005012
    CSI 4.36
    rCSI 4.35%
    PRS 65.68
  • retinal rod cell CL0000604
    CSI 4.03
    rCSI 7.11%
    PRS 68.13
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.96
    rCSI 3.01%
    PRS 84.85
  • dendritic cell, human CL0001056
    CSI 3.8
    rCSI 5.83%
    PRS 81.3
  • placental villous trophoblast CL2000060
    CSI 3.68
    rCSI 5.69%
    PRS 71.07
  • unswitched memory B cell CL0000970
    CSI 3.61
    rCSI 3.04%
    PRS 86.83
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 3.52
    rCSI 4.25%
    PRS 80.8
  • double negative thymocyte CL0002489
    CSI 3.52
    rCSI 2.45%
    PRS 83.49
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.18
    rCSI 2.45%
    PRS 74.11
  • mesodermal cell CL0000222
    CSI 3.16
    rCSI 3.79%
    PRS 70.13
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.98
    rCSI 2.01%
    PRS 85.21
  • interstitial cell of Cajal CL0002088
    CSI 2.97
    rCSI 3.78%
    PRS 77.73
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.91
    rCSI 2.26%
    PRS 75.39
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.84
    rCSI 7.33%
    PRS 66.94
  • pancreatic D cell CL0000173
    CSI 2.75
    rCSI 2.71%
    PRS 74.75
  • Kupffer cell CL0000091
    CSI 2.69
    rCSI 6.16%
    PRS 72.72
  • ON-bipolar cell CL0000749
    CSI 2.69
    rCSI 4%
    PRS 72.67
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.65
    rCSI 3.3%
    PRS 51.31
  • respiratory suprabasal cell CL4033048
    CSI 2.64
    rCSI 3.38%
    PRS 76.24
  • melanocyte CL0000148
    CSI 2.64
    rCSI 1.95%
    PRS 64.83
  • pro-B cell CL0000826
    CSI 2.62
    rCSI 2.17%
    PRS 74.53
  • Mueller cell CL0000636
    CSI 2.59
    rCSI 5.91%
    PRS 63.32
  • epithelial cell of lung CL0000082
    CSI 2.54
    rCSI 2.11%
    PRS 72.35
  • central nervous system neuron CL2000029
    CSI 2.53
    rCSI 18.61%
    PRS 58.74
  • T follicular helper cell CL0002038
    CSI 2.43
    rCSI 1.82%
    PRS 85.92
  • interneuron CL0000099
    CSI 2.39
    rCSI 4.79%
    PRS 61.34
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.31
    rCSI 5.17%
    PRS 53.83
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.3
    rCSI 3.67%
    PRS 75.99
  • mesenchymal cell CL0008019
    CSI 2.18
    rCSI 5.54%
    PRS 65.62
  • group 3 innate lymphoid cell CL0001071
    CSI 2.18
    rCSI 1.64%
    PRS 78.02
  • CD4-positive helper T cell CL0000492
    CSI 2.17
    rCSI 1.64%
    PRS 85.19
  • renal alpha-intercalated cell CL0005011
    CSI 2.16
    rCSI 2.89%
    PRS 79.92
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.15
    rCSI 5.6%
    PRS 72.59
  • mature B cell CL0000785
    CSI 2.11
    rCSI 1.84%
    PRS 82.51
  • vascular leptomeningeal cell CL4023051
    CSI 2.1
    rCSI 3.68%
    PRS 64.66
  • intestinal epithelial cell CL0002563
    CSI 2.09
    rCSI 2.18%
    PRS 69.77
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.08
    rCSI 13%
    PRS 63.46
  • colon epithelial cell CL0011108
    CSI 2.06
    rCSI 2.16%
    PRS 69.17
  • choroid plexus epithelial cell CL0000706
    CSI 2.05
    rCSI 3.36%
    PRS 61.01
  • granulocyte CL0000094
    CSI 2.02
    rCSI 3.09%
    PRS 80.75
  • cerebral cortex endothelial cell CL1001602
    CSI 1.97
    rCSI 3.41%
    PRS 62.63
  • neural crest cell CL0011012
    CSI 1.96
    rCSI 1.55%
    PRS 59.48
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.95
    rCSI 4.46%
    PRS 66.98
  • hepatic stellate cell CL0000632
    CSI 1.95
    rCSI 7.3%
    PRS 63.95
  • direct pathway medium spiny neuron CL4023026
    CSI 1.95
    rCSI 46.6%
    PRS 52.12
  • ciliated epithelial cell CL0000067
    CSI 1.94
    rCSI 1.71%
    PRS 60.32
  • hepatocyte CL0000182
    CSI 1.93
    rCSI 3.45%
    PRS 71.5
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.92
    rCSI 6%
    PRS 55.05
  • cardiac muscle cell CL0000746
    CSI 1.83
    rCSI 2.63%
    PRS 61.45
  • radial glial cell CL0000681
    CSI 1.83
    rCSI 2.55%
    PRS 70.66
  • OFF-bipolar cell CL0000750
    CSI 1.81
    rCSI 2.48%
    PRS 75.98
  • ionocyte CL0005006
    CSI 1.81
    rCSI 1.94%
    PRS 72.73
  • ciliated cell CL0000064
    CSI 1.8
    rCSI 2.92%
    PRS 67.74
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.77
    rCSI 8.9%
    PRS 84.42
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.75
    rCSI 2.81%
    PRS 55.1
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.72
    rCSI 4.36%
    PRS 61.74
  • retinal ganglion cell CL0000740
    CSI 1.72
    rCSI 3.79%
    PRS 57.72
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.71
    rCSI 41.27%
    PRS 52.75
  • common dendritic progenitor CL0001029
    CSI 1.7
    rCSI 2.14%
    PRS 81.87
  • promyelocyte CL0000836
    CSI 1.69
    rCSI 2.44%
    PRS 79.79
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.67
    rCSI 6.01%
    PRS 51.38
  • extravillous trophoblast CL0008036
    CSI 1.66
    rCSI 2.05%
    PRS 69.34
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.65
    rCSI 1.49%
    PRS 69.47
  • lung ciliated cell CL1000271
    CSI 1.65
    rCSI 1.9%
    PRS 63.27
  • peripheral nervous system neuron CL2000032
    CSI 1.65
    rCSI 2.24%
    PRS 63.35
  • lung neuroendocrine cell CL1000223
    CSI 1.64
    rCSI 2.42%
    PRS 76.75
  • chondrocyte CL0000138
    CSI 1.63
    rCSI 2.59%
    PRS 64.62
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.61
    rCSI 1.86%
    PRS 64.33
  • ependymal cell CL0000065
    CSI 1.61
    rCSI 3.26%
    PRS 50.2
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.57
    rCSI 4.65%
    PRS 74.01
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.54
    rCSI 1.99%
    PRS 54.62
  • vascular associated smooth muscle cell CL0000359
    CSI 1.47
    rCSI 4.76%
    PRS 70.96
  • intermediate monocyte CL0002393
    CSI 1.45
    rCSI 2.19%
    PRS 77.31
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.43
    rCSI 1.71%
    PRS 53.11
  • pancreatic acinar cell CL0002064
    CSI 1.38
    rCSI 1.83%
    PRS 78.31
  • rod bipolar cell CL0000751
    CSI 1.32
    rCSI 2.38%
    PRS 65.21
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.31
    rCSI 3.77%
    PRS 89.81
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.26
    rCSI 2.23%
    PRS 52.34
  • glioblast CL0000030
    CSI 1.25
    rCSI 2%
    PRS 63.79
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.24
    rCSI 7.33%
    PRS 54.34
  • retinal cone cell CL0000573
    CSI 1.18
    rCSI 1.89%
    PRS 61.5
  • lung pericyte CL0009089
    CSI 1.17
    rCSI 3.08%
    PRS 80.24
  • retinal bipolar neuron CL0000748
    CSI 1.09
    rCSI 2.04%
    PRS 59.86
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.08
    rCSI 1.81%
    PRS 53.26
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1
    rCSI 2.43%
    PRS 51.57
  • retina horizontal cell CL0000745
    CSI 0.96
    rCSI 1.46%
    PRS 68.6
  • glial cell CL0000125
    CSI 0.85
    rCSI 3.22%
    PRS 62.44
  • blood vessel smooth muscle cell CL0019018
    CSI 0.74
    rCSI 6.05%
    PRS 65.56
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.71
    rCSI 2.68%
    PRS 53.77
  • amacrine cell CL0000561
    CSI 0.69
    rCSI 2.01%
    PRS 61.15
  • endothelial cell of placenta CL0009092
    CSI 0.68
    rCSI 3.34%
    PRS 81.83
  • type EC enteroendocrine cell CL0000577
    CSI 0.59
    rCSI 2.11%
    PRS 78.21
  • podocyte CL0000653
    CSI 0.59
    rCSI 2.63%
    PRS 72.4
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.54
    rCSI 1.68%
    PRS 57.54

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.
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 [CNOT9](/details-gene/9125), also known as CCR4-NOT transcription complex subunit 9 or RQCD1, is a protein-coding gene located on chromosome 2q35. It is a core component of the highly conserved CCR4-NOT complex, a major regulator of eukaryotic gene expression primarily involved in mRNA deadenylation, which is a key step in mRNA decay ([Link](https://doi.org/10.4161/rna.23065)). Beyond its role in post-transcriptional control, [CNOT9](/details-gene/9125) also functions as a nuclear receptor coactivator, influencing transcription directly ([Link](https://doi.org/10.1074/jbc.m706986200)). **Overall**, expression data indicates that [CNOT9](/details-gene/9125) is a gene of fundamental importance, showing its highest significance in highly proliferative cells such as [transit amplifying cells](/details-cell/CL0009010) and a wide array of specialized cell types, including [enteroendocrine cells](/details-cell/CL0000164) and various adaptive immune cells like [mature alpha-beta T cells](/details-cell/CL0000791). This suggests a pleiotropic role in maintaining cellular homeostasis, proliferation, and differentiated function. ## Cellular Roles and Expression Landscape The expression profile of [CNOT9](/details-gene/9125) highlights its critical function in diverse cellular contexts. **Overall**, its most significant expression is observed in [transit amplifying cells](/details-cell/CL0009010) (CSI: 13.28), which are rapidly dividing progenitor cells, suggesting a crucial role for [CNOT9](/details-gene/9125) in cell cycle progression and tissue renewal. The gene also demonstrates high significance in several specialized secretory and endocrine cell types. This includes high CSI scores in [enteroendocrine cells](/details-cell/CL0000164) (CSI: 9.18) and [type B pancreatic cells](/details-cell/CL0000169) (CSI: 5.00), which may relate to its function as a nuclear receptor coactivator involved in hormone-regulated gene expression. Furthermore, [CNOT9](/details-gene/9125) appears to be a key player within the immune system. It shows significant expression across multiple lineages, including [mature alpha-beta T cells](/details-cell/CL0000791) (CSI: 4.59), [effector CD8-positive, alpha-beta T cells](/details-cell/CL0001050) (CSI: 3.96), [dendritic cells](/details-cell/CL0001056) (CSI: 3.80), and [unswitched memory B cells](/details-cell/CL0000970) (CSI: 3.61). This broad but significant expression pattern across different immune cell types suggests a fundamental role in regulating immune responses, potentially by controlling the stability of mRNAs encoding cytokines and other effector molecules. ## Pathways and Molecular Function [CNOT9](/details-gene/9125) functions as an integral component of the [Ccr4-not complex](/details-go/GO0030014), a master regulator of mRNA metabolism. Its primary annotated function relates to the post-transcriptional control of gene expression through 'Nuclear-transcribed mrna poly(a) tail shortening' ([GO:0000289](https://www.ebi.ac.uk/QuickGO/term/GO:0000289)) and 'Deadenylation-dependent mrna decay' ([R-HSA-429914](https://reactome.org/content/detail/R-HSA-429914)). This role is fundamental to controlling the lifespan of transcripts in all the cell types where it is highly expressed. The gene's involvement in transcriptional regulation is also well-documented. It participates in 'Positive regulation of dna-templated transcription' ([GO:0045893](https://www.ebi.ac.uk/QuickGO/term/GO:0045893)) and acts as a 'Nuclear receptor coactivator' ([GO:0030374](https://www.ebi.ac.uk/QuickGO/term/GO:0030374)). This dual functionality is consistent with its high significance in both proliferative cells, which require tight transcriptional control, and endocrine cells, which depend on nuclear receptor signaling. Its connection to the 'Transcriptional regulation by tp53' pathway ([R-HSA-3700989](https://reactome.org/content/detail/R-HSA-3700989)) aligns with its high CSI in [transit amplifying cells](/details-cell/CL0009010), where p53 plays a key role in managing cell fate decisions. Additionally, its role in the 'Cytokine-mediated signaling pathway' ([GO:0019221](https://www.ebi.ac.uk/QuickGO/term/GO:0019221)) supports its importance in the various immune cell populations where it is significantly expressed. ## Research Directions The widespread and significant expression of [CNOT9](/details-gene/9125) in both rapidly proliferating and terminally differentiated cells suggests it acts as a central hub for gene regulation. Future research should focus on dissecting its cell-type-specific functions. **Proposed Hypotheses:** 1. Given its top significance in [transit amplifying cells](/details-cell/CL0009010) and its link to TP53 pathways, [CNOT9](/details-gene/9125) may function as a critical gatekeeper for cellular differentiation in epithelial tissues. It likely achieves this by modulating the stability of key mRNAs that govern the transition from a proliferative to a differentiated state. 2. Based on its high significance in multiple adaptive immune cell subsets ([T cells](/details-cell/CL0000791), [B cells](/details-cell/CL0000970), [dendritic cells](/details-cell/CL0001056)) and its role in cytokine signaling pathways, [CNOT9](/details-gene/9125) likely regulates the magnitude and duration of an immune response by controlling the post-transcriptional fate of transcripts encoding key cytokines, chemokines, and their receptors. **Experimental Approach:** To test the first hypothesis, a compelling experiment would involve using a 3D intestinal organoid culture system, which recapitulates the stem cell niche and differentiation process. CRISPR interference (CRISPRi) could be used to specifically knock down [CNOT9](/details-gene/9125) expression in these organoids. The impact on cellular dynamics could be assessed using single-cell RNA sequencing to quantify changes in the proportions of stem cells, [transit amplifying cells](/details-cell/CL0009010), and various differentiated cell lineages. Concurrently, RNA decay assays (e.g., using actinomycin D to halt transcription) followed by qPCR or RNA-seq could be performed to directly measure changes in the half-life of specific differentiation-associated mRNAs. **Therapeutic Potential:** As an essential component of the CCR4-NOT complex, systemic targeting of [CNOT9](/details-gene/9125) would likely lead to significant toxicity due to its fundamental role in gene regulation across many cell types. However, its high expression in rapidly dividing [transit amplifying cells](/details-cell/CL0009010) suggests it could be a context-dependent therapeutic target in hyperproliferative diseases such as colorectal cancer, where these cells are the origin of tumors. The therapeutic strategy would be inhibition. Since [CNOT9](/details-gene/9125) is an intracellular protein, it is not amenable to antibody-based therapies, making the development of specific small-molecule inhibitors a more viable, though challenging, path forward.

Genular Protein ID: 1402360308

Symbol: CNOT9_HUMAN

Name: Cell differentiation protein RQCD1 homolog

UniProtKB Accession Codes:

Q92600 B2RPI0 B5MDQ4 B7Z1E5 Q96IX4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 4 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 10 PDBsum 10 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 4 RefSeq 3 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9447985

Title: Novel factor highly conserved among eukaryotes controls sexual development in fission yeast.

PubMed ID: 9447985

DOI: 10.1128/mcb.18.2.887

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 18180299

Title: Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

PubMed ID: 18180299

DOI: 10.1074/jbc.m706986200

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23232451

Title: C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex.

PubMed ID: 23232451

DOI: 10.4161/rna.23065

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 17189474

Title: Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties.

PubMed ID: 17189474

DOI: 10.1110/ps.062600507

Sequence Information:

  • Length: 299
  • Mass: 33631
  • Checksum: CFA0E108F5E9D8F2
  • Sequence:
    • MHSLATAAPV PTTLAQVDRE KIYQWINELS SPETRENALL ELSKKRESVP DLAPMLWHSF 
GTIAALLQEI VNIYPSINPP TLTAHQSNRV CNALALLQCV ASHPETRSAF LAAHIPLFLY 
PFLHTVSKTR PFEYLRLTSL GVIGALVKTD EQEVINFLLT TEIIPLCLRI MESGSELSKT 
VATFILQKIL LDDTGLAYIC QTYERFSHVA MILGKMVLQL SKEPSARLLK HVVRCYLRLS 
DNPRAREALR QCLPDQLKDT TFAQVLKDDT TTKRWLAQLV KNLQEGQVTD PRGIPLPPQ