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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNOT10
CCR4-NOT transcription complex subunit 10
Chromosome 3 · 3p22.3
NCBI Gene: 25904Ensembl: ENSG00000182973.21HGNC: HGNC:23817UniProt: Q9H9A5
81PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membraneprotein bindingCCR4-NOT complexnegative regulation of translationneurodegenerative diseasenephrotic syndromeattention deficit hyperactivity disorderhereditary attention deficit-hyperactivity disorder
✦AI Summary

CNOT10 is a component of the CCR4-NOT complex, one of the major cellular mRNA deadenylases 1. As part of the N-terminal CNOT1-CNOT10-CNOT11 module, CNOT10 functions as a structural platform for protein-protein interactions, with the CNOT11 antenna domain serving as a conserved binding site for regulatory factors like GGNBP2 1. The CNOT10/CNOT11 module is hierarchically assembled and conserved across eukaryotes except fungi 23. CNOT10 is essential for complex integrity and mRNA decay; its depletion destabilizes the NOT complex and prevents CAF1 deadenylase recruitment to target mRNAs 4. Beyond mRNA degradation, CNOT10 participates in miRNA-mediated repression and translational regulation 5. Recent evidence reveals CNOT10's involvement in innate immunity: CNOT10 regulates MDA5 sensing of unedited double-stranded RNA through interaction with GGNBP2, modulating type I interferon signaling and autoinflammatory responses 6. In stem cell differentiation, CNOT10 depletion affects expression of neuronal and pluripotency-related genes 5. While CNOT10 variants have been identified in regions of homozygosity in Müllerian aplasia patients 7, direct pathogenic roles require further investigation. CNOT10's multifaceted functions make it a central regulator of post-transcriptional gene expression.

Sources cited
1
CNOT10 is part of the N-terminal CNOT1-CNOT10-CNOT11 module that forms a structural platform for protein-protein interactions, with GGNBP2 as a conserved interacting partner
PMID: 36586408
2
CNOT10 regulates MDA5 sensing of unedited cellular dsRNA and modifies type I interferon signaling and autoinflammatory responses
PMID: 39576872
3
The NOT1-NOT10-NOT11 module has a conserved, flexible structure with hierarchical assembly where NOT11 binds NOT10, which then organizes binding to NOT1
PMID: 37460791
4
CNOT10 is essential for NOT complex integrity and mRNA decay; its depletion destabilizes the complex and prevents CAF1 deadenylase recruitment to mRNAs
PMID: 23221646
5
CNOT10 participates in stem cell differentiation, with its depletion affecting expression of neuronal and pluripotency-related genes
PMID: 33104214
6
CNOT10 interacts with CNOT11 and is required for CNOT10 association with the CCR4-NOT complex; the CNOT10/CNOT11 module is conserved in all eukaryotes except fungi
PMID: 23232451
7
CNOT10 resides within regions of homozygosity identified in Müllerian aplasia patients, though causation is not established
PMID: 29434669
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
nephrotic syndromeOpen Targets
0.27Weak
attention deficit hyperactivity disorderOpen Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.06Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.05Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.05Suggestive
schizophrenia 15Open Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
autismOpen Targets
0.05Suggestive
Phelan-McDermid syndromeOpen Targets
0.04Suggestive
Potocki-Lupski syndromeOpen Targets
0.03Suggestive
X-linked non-syndromic intellectual disabilityOpen Targets
0.03Suggestive
X-linked dominant intellectual disability - epilepsy syndromeOpen Targets
0.03Suggestive
hypertensionOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
leukemiaOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
melanomaOpen Targets
0.00Suggestive
ovarian cancerOpen Targets
0.00Suggestive
ThymomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MMP7Protein interaction100%CNOT2Protein interaction100%CNOT4Protein interaction100%CNOT8Protein interaction100%TOB1Protein interaction100%CPEB3Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
57%
Lung
54%
Liver
49%
Heart
47%
Brain
43%
Gene Interaction Network
Click a node to explore
CNOT10MMP7CNOT2CNOT4CNOT8TOB1CPEB3
PROTEIN STRUCTURE
Preparing viewer…
PDB8FY3 · 2.88 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.25 [0.17–0.41]
RankingsWhere CNOT10 stands among ~20K protein-coding genes
  • #5,851of 20,598
    Most Researched81
  • #2,058of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedCNOT10
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions.
PMID: 36586408
Cell Rep · 2023
1.00
2
GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing.
PMID: 39576872
Sci Immunol · 2024
0.90
3
Structure and assembly of the NOT10:11 module of the CCR4-NOT complex.
PMID: 37460791
Commun Biol · 2023
0.80
4
Trypanosome CNOT10 is essential for the integrity of the NOT deadenylase complex and for degradation of many mRNAs.
PMID: 23221646
Nucleic Acids Res · 2013
0.70
5
RNF219 interacts with CCR4-NOT in regulating stem cell differentiation.
PMID: 33104214
J Mol Cell Biol · 2020
0.60