CNOT9: CCR4-NOT Transcription Complex Subunit 9
A key regulator of mRNA deadenylation and gene expression, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | CNOT9 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 9125 ncbi.nlm.nih.gov/gene/9125 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | Q9Y2X0 |
| OMIM ID | 604083 |
| HGNC ID | 14075 |
| Aliases | RCD-8, CAF40, POP2B, QM, Smad anchor for receptor activation (SARA) |
Description
CNOT9 encodes a subunit of the CCR4-NOT complex, a major regulator of mRNA deadenylation and turnover. The protein interacts with the NOT module and is involved in post-transcriptional gene regulation, including mRNA decay, translational repression, and signaling pathways such as TGF-β. It is also known as RCD-8 (required for cell differentiation) and CAF40.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | CNOT9 overexpression may promote tumorigenesis by altering mRNA stability of oncogenes and tumor suppressors. | PMID: 23431136 |
| Colorectal cancer | CNOT9 mutations and altered expression are associated with poor prognosis and metastasis. | PMID: 25686104 |
| Developmental disorders | Homozygous loss-of-function mutations in CNOT9 cause a syndromic neurodevelopmental disorder with intellectual disability and facial dysmorphism. | PMID: 31006511 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Brain | 10.5 | Medium |
| Liver | 8.3 | Medium |
| Heart | 6.1 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.0 | Embryonic kidney cells; high expression |
| HeLa | 9.8 | Cervical cancer cells; moderate expression |
| MCF7 | 7.5 | Breast cancer cells; moderate expression |
| HepG2 | 6.2 | Liver cancer cells; low expression |
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.328C>T (p.Arg110*) | Nonsense | Rare | Premature stop; loss of function |
| c.502G>A (p.Gly168Arg) | Missense | Rare | Impaired protein stability and complex assembly |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in CNOT9 lead to truncated or unstable proteins, reducing CCR4-NOT complex activity and mRNA deadenylation.
Gain of Function (GOF)
Not well characterized; overexpression in some cancers may act as a gain-of-function by increasing turnover of specific mRNAs.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly168Arg) may disrupt complex assembly and exert dominant-negative effects on mRNA decay.
View complete mutation data：
Gene Ontology (GO)
| • mRNA deadenylation | • regulation of mRNA stability |
| • negative regulation of translation | • TGF-beta receptor signaling pathway |
| • cytoplasm | • CCR4-NOT complex |
Pathways
• mRNA surveillance pathway
• TGF-beta signaling pathway
• RNA degradation
Protein Summary
CNOT9 is a 299-amino acid protein containing a CAF40 domain that mediates interaction with the NOT module of the CCR4-NOT complex. It functions as a scaffold and regulator of deadenylation, influencing mRNA stability and translation. The protein also shuttles between nucleus and cytoplasm and participates in TGF-β signaling by interacting with SMAD proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT9 Knockout HEK293 Cell Line | EDJ-KQ2609 | Human | 9125 | Details Get a Quote |
| CNOT9 Knockout A-549 Cell Line | EDJ-KQ23325 | Human | 9125 | Details Get a Quote |
| CNOT9 Knockout HCT 116 Cell Line | EDJ-KQ23326 | Human | 9125 | Details Get a Quote |
| CNOT9 Knockout HeLa Cell Line | EDJ-KQ23327 | Human | 9125 | Details Get a Quote |
