CNOT2: A Key Regulator of Transcription and mRNA Decay
Comprehensive gene card for CNOT2, a subunit of the CCR4-NOT complex involved in gene expression control and linked to developmental disorders and cancer.
Gene Information Card
| Symbol | CNOT2 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.21 |
| NCBI Gene ID | 4848 ncbi.nlm.nih.gov/gene/4848 |
| Ensembl ID | ENSG00000111596 |
| UniProt ID | Q9NZN8 |
| OMIM ID | 604909 |
| HGNC ID | 7878 |
| Aliases | CDC36, NOT2, HSPC131 |
Description
CNOT2 encodes a subunit of the CCR4-NOT complex, a major regulator of gene expression. The complex controls transcription initiation, mRNA deadenylation, and mRNA decay. CNOT2 is essential for complex stability and mediates interactions with transcription factors and RNA-binding proteins. It plays roles in cell proliferation, differentiation, and development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 76 (MRD76) | Loss-of-function mutations in CNOT2 disrupt CCR4-NOT complex function, impairing mRNA regulation and neuronal gene expression. | ClinVar; OMIM #619512 |
| Colorectal cancer | CNOT2 overexpression correlates with poor prognosis; promotes cell proliferation and metastasis via Wnt/β-catenin pathway activation. | COSMIC; PMID: 31591470 |
| Breast cancer | CNOT2 amplification and overexpression linked to tumor progression and tamoxifen resistance. | COSMIC; PMID: 30108147 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 14.2 | Medium |
| Brain (cerebellum) | 10.5 | Medium |
| Heart | 8.1 | Medium |
| Liver | 6.3 | Low |
| Lung | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.1 | Cervical cancer cell line |
| K562 | 9.8 | Leukemia cell line |
| HepG2 | 7.4 | Hepatocellular carcinoma cell line |
| A549 | 6.5 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; predicted loss of function |
| c.325C>T (p.Arg109*) | Nonsense | Rare | Premature stop; loss of function |
| c.632_633del (p.Glu211Glyfs*12) | Frameshift | Rare | Loss of function |
| c.1045G>A (p.Glu349Lys) | Missense | Rare | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations in CNOT2 are classified as loss-of-function, leading to haploinsufficiency and intellectual disability.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CNOT2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting CCR4-NOT complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • CCR4-NOT complex (GO:0030014) | • magnesium ion binding (GO:0000287) |
| • nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288) | • regulation of transcription, DNA-templated (GO:0006355) |
Pathways
• mRNA surveillance pathway (KEGG: hsa03015)
• RNA degradation (KEGG: hsa03018)
• Cell cycle (Reactome: R-HSA-1640170)
Protein Summary
CNOT2 is a 540-amino-acid protein (60 kDa) containing a NOT2/NOT3/NOT5 domain essential for CCR4-NOT complex integrity. It localizes to the nucleus and interacts with transcription factors (e.g., TBP, TFIID) and RNA-binding proteins. CNOT2 is required for mRNA deadenylation and decay, and its dysregulation contributes to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
