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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNOT8
CCR4-NOT transcription complex subunit 8
Chromosome 5 · 5q33.2
NCBI Gene: 9337Ensembl: ENSG00000155508.14HGNC: HGNC:9207UniProt: B7Z9U0
78PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
3'-5'-RNA exonuclease activitypoly(A)-specific ribonuclease activityprotein bindingpositive regulation of cell population proliferationadolescent idiopathic scoliosiscervical cancerinfectionendocrine system disease
✦AI Summary

CNOT8 is a catalytic subunit of the CCR4-NOT deadenylase complex with 3'-5' poly(A) exoribonuclease activity 1. As part of the CCR4-NOT core complex, CNOT8 mediates mRNA degradation through deadenylation, the removal of poly(A) tails from mRNAs 2. CNOT8 functions in multiple interconnected processes: it participates in miRNA-mediated gene silencing through direct recruitment by YTHDF2 to destabilize m(6)A-modified RNAs 3, and it exhibits partial functional redundancy with CNOT7 in regulating cell proliferation 1. CNOT8 interacts with anti-proliferative BTG family proteins to modulate their biological activities 4. Beyond mRNA decay, CNOT8 contributes to induced pluripotent stem cell generation through deadenylation-dependent regulation of reprogramming-associated mRNAs 5, and it plays a role in cellular responses to ionizing radiation-induced DNA damage 6. Clinically, CNOT8 expression has been identified as a prognostic factor in clear cell renal cell carcinoma immunotherapy outcomes 7. The complex functions of CNOT8 reflect its central role in post-transcriptional gene expression control across diverse cellular contexts.

Sources cited
1
CNOT8 possesses deadenylase activity and shows partial redundancy with CNOT7 in regulating cell proliferation
PMID: 19605561
2
CNOT8 is part of the CCR4-NOT core complex with conserved deadenylation catalytic function
PMID: 28271483
3
CNOT8 participates in YTHDF2-mediated deadenylation of m(6)A-containing RNAs
PMID: 27558897
4
CNOT8 interacts with BTG/Tob family proteins in mRNA deadenylation and gene expression regulation
PMID: 19746446
5
CNOT8 deadenylase activity contributes to induced pluripotent stem cell generation
PMID: 27037025
6
CNOT8 is involved in cellular responses to ionizing radiation-induced DNA damage
PMID: 33178865
7
CNOT8 expression is associated with immunotherapy prognosis in clear cell renal cell carcinoma
PMID: 39288623
Disease Associationsⓘ20
adolescent idiopathic scoliosisOpen Targets
0.08Suggestive
cervical cancerOpen Targets
0.07Suggestive
infectionOpen Targets
0.06Suggestive
endocrine system diseaseOpen Targets
0.06Suggestive
cholelithiasisOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
brain cancerOpen Targets
0.03Suggestive
central nervous system cancerOpen Targets
0.03Suggestive
nervous system cancerOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.03Suggestive
Yersinia pestis infectious diseaseOpen Targets
0.03Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
head and neck squamous cell carcinomaOpen Targets
0.02Suggestive
squamous cell carcinomaOpen Targets
0.02Suggestive
mycosis fungoidesOpen Targets
0.02Suggestive
systemic lupus erythematosusOpen Targets
0.02Suggestive
bacterial diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DDX6Protein interaction100%CNOT2Protein interaction100%CNOT3Protein interaction100%CNOT4Protein interaction100%CNOT9Protein interaction100%CNOT10Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
58%
Brain
50%
Heart
29%
Ovary
29%
Liver
23%
Gene Interaction Network
Click a node to explore
CNOT8DDX6CNOT2CNOT3CNOT4CNOT9CNOT10
PROTEIN STRUCTURE
Preparing viewer…
PDB9E7U · 3.50 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.05Tolerant
Observed/Expected LoF0.48 [0.31–0.78]
RankingsWhere CNOT8 stands among ~20K protein-coding genes
  • #6,057of 20,598
    Most Researched78
  • #6,322of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedCNOT8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex.
PMID: 27558897
Nat Commun · 2016
1.00
2
Acute multi-level response to defective de novo chromatin assembly in S-phase.
PMID: 39536749
Mol Cell · 2024
0.90
3
The Ccr4-NOT deadenylase subunits CNOT7 and CNOT8 have overlapping roles and modulate cell proliferation.
PMID: 19605561
Mol Biol Cell · 2009
0.80
4
The mammalian anti-proliferative BTG/Tob protein family.
PMID: 19746446
J Cell Physiol · 2010
0.70
5
Prognostic significance of immune evasion-related genes in clear cell renal cell carcinoma immunotherapy.
PMID: 39288623
Int Immunopharmacol · 2024
0.60