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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CNOT9
CCR4-NOT transcription complex subunit 9
Chromosome 2 Β· 2q35
NCBI Gene: 9125Ensembl: ENSG00000144580.16HGNC: HGNC:10445UniProt: D5MQE1
78PubMed Papers
20Diseases
0Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
transcription coactivator activityepidermal growth factor receptor bindingprotein bindingkinase bindingmelanomaepilepsycutaneous melanomaIntellectual disability
✦AI Summary

CNOT9 is a core component of the CCR4-NOT deadenylase complex, which plays essential roles in mRNA metabolism and gene regulation 1. The protein functions as a scaffold that facilitates interactions between the CCR4-NOT complex and various regulatory proteins through tryptophan-binding pockets 2. CNOT9 directly binds to the DUF3819 domain of CNOT1, the scaffold protein of the complex, and this interaction stimulates deadenylation activity by the nuclease module 1. In microRNA-mediated silencing, CNOT9 serves as a critical effector by binding tryptophan-rich motifs in GW182/TNRC6 proteins, linking miRNA target recognition to mRNA deadenylation and decay 23. Similarly, CNOT9 interacts with tristetraprolin (TTP) through conserved tryptophan residues, enabling recruitment of the CCR4-NOT complex for AU-rich element-mediated mRNA decay 4. The protein also functions in transcriptional regulation and plant light signaling pathways 5. Clinically, de novo missense variants in CNOT9 cause neurodevelopmental disorders characterized by intellectual disability, seizures, muscular hypotonia, and facial dysmorphism, establishing CNOT9 as a disease gene 6. The tryptophan-binding properties of CNOT9 are fundamental to its diverse regulatory functions across multiple cellular pathways.

Sources cited
1
CNOT9 binds to CNOT1 DUF3819 domain and stimulates deadenylation activity
PMID: 30309886
2
CNOT9 contains tryptophan-binding pockets that interact with TNRC6/GW182 proteins in miRNA silencing
PMID: 24768540
3
CNOT9 binds to GW182 N-terminal domain through tryptophan-rich regions
PMID: 35822830
4
CNOT9 interacts with tristetraprolin through tryptophan residues for mRNA decay
PMID: 29291391
5
CNOT9 functions in plant phytochrome A-mediated light signaling
PMID: 33783355
6
De novo CNOT9 variants cause neurodevelopmental disorder with intellectual disability and seizures
PMID: 37092538
Disease Associationsβ“˜20
melanomaOpen Targets
0.38Weak
epilepsyOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.37Weak
neuroendocrine neoplasmOpen Targets
0.31Weak
mouth diseaseOpen Targets
0.12Weak
osteoarthritis, kneeOpen Targets
0.12Weak
spinal stenosisOpen Targets
0.11Weak
obesityOpen Targets
0.07Suggestive
Abnormality of the skeletal systemOpen Targets
0.07Suggestive
Back painOpen Targets
0.06Suggestive
ArthralgiaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
lymphatic malformation 11Open Targets
0.03Suggestive
breast cancerOpen Targets
0.02Suggestive
triple-negative breast cancerOpen Targets
0.02Suggestive
retinal degenerationOpen Targets
0.02Suggestive
Neurodevelopmental disorderOpen Targets
0.01Suggestive
retinitis pigmentosaOpen Targets
0.01Suggestive
ThymomaOpen Targets
0.01Suggestive
Pathogenic Variants4
NM_005444.3(CNOT9):c.680G>A (p.Arg227His)Pathogenic
not provided|CNOT9-associated neurodevelopmental disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 227
NM_005444.3(CNOT9):c.874C>T (p.Arg292Trp)Pathogenic
not provided|CNOT9-associated neurodevelopmental disorder|See cases
β˜…β˜…β˜†β˜†2025β†’ Residue 292
NM_005444.3(CNOT9):c.392C>T (p.Pro131Leu)Likely pathogenic
CNOT9-associated neurodevelopmental disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 131
NM_005444.3(CNOT9):c.136C>G (p.Arg46Gly)Likely pathogenic
CNOT9-associated neurodevelopmental disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 46
View on ClinVar β†—
Related Genes
MMP7Protein interaction100%CNOT4Protein interaction100%CNOT8Protein interaction100%CNOT6LProtein interaction100%TENT4AProtein interaction100%TENT4BProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
52%
Brain
52%
Ovary
50%
Lung
49%
Heart
36%
Gene Interaction Network
Click a node to explore
CNOT9MMP7CNOT4CNOT8CNOT6LTENT4ATENT4B
PROTEIN STRUCTURE
Preparing viewer…
PDB4CRU Β· 1.65 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.52Moderately Constrained
pLIβ“˜
0.96Intolerant
Observed/Expected LoF0.28 [0.16–0.52]
RankingsWhere CNOT9 stands among ~20K protein-coding genes
  • #6,058of 20,598
    Most Researched78
  • #3,764of 5,498
    Most Pathogenic Variants4
  • #3,243of 17,882
    Most Constrained (LOEUF)0.52 Β· top quartile
Genes detectedCNOT9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
N-terminal Ago-binding domain of GW182 contains a tryptophan-rich region that confer binding to the CCR4-NOT complex.
PMID: 35822830
Genes Cells Β· 2022
1.00
2
The central region of CNOT1 and CNOT9 stimulates deadenylation by the Ccr4-Not nuclease module.
PMID: 30309886
Biochem J Β· 2018
0.90
3
Structural and biochemical insights to the role of the CCR4-NOT complex and DDX6 ATPase in microRNA repression.
PMID: 24768538
Mol Cell Β· 2014
0.80
4
De novo variants in CNOT9 cause a neurodevelopmental disorder with or without epilepsy.
PMID: 37092538
Genet Med Β· 2023
0.70
5
Uncovering a novel function of the CCR4-NOT complex in phytochrome A-mediated light signalling in plants.
PMID: 33783355
Elife Β· 2021
0.60