CNOT6 (CCR4-NOT Transcription Complex Subunit 6) - Structure, Function, and Clinical Relevance
A comprehensive biomedical overview of the CNOT6 gene, its protein product, expression patterns, mutations, and associated diseases, based on authoritative genomic and proteomic databases.
Gene Information Card
| Symbol | CNOT6 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 57472 ncbi.nlm.nih.gov/gene/57472 |
| Ensembl ID | ENSG00000113300 |
| UniProt ID | Q9ULM6 |
| OMIM ID | 608951 |
| HGNC ID | 14103 |
| Aliases | CCR4, CCR4A, Ccr4a, FLJ11072, MGC126562, MGC126564 |
Description
CNOT6 encodes the CCR4-NOT transcription complex subunit 6, a catalytic component of the CCR4-NOT deadenylase complex. This complex is involved in mRNA deadenylation, a key step in mRNA decay and translational regulation. CNOT6 possesses 3'-5' exonuclease activity and is essential for the removal of poly(A) tails, thereby influencing gene expression post-transcriptionally. The protein is widely expressed and plays roles in various cellular processes including cell cycle, differentiation, and stress response. Mutations and dysregulation of CNOT6 have been implicated in several diseases, particularly cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Altered CNOT6 expression may affect mRNA stability of oncogenes or tumor suppressors, contributing to tumorigenesis. | COSMIC database lists CNOT6 mutations in colorectal cancer samples; studies suggest dysregulation in tumor tissues. |
| Breast cancer | CNOT6 may influence estrogen receptor signaling via mRNA decay of specific targets; expression changes correlate with prognosis. | COSMIC and literature reports indicate CNOT6 alterations in breast cancer; functional studies show impact on cell proliferation. |
| Hepatocellular carcinoma | CNOT6-mediated deadenylation may regulate genes involved in cell cycle and apoptosis, affecting tumor growth. | COSMIC lists CNOT6 mutations in liver cancer; experimental evidence shows altered expression in HCC cell lines. |
| Lung cancer | CNOT6 mutations or expression changes could affect mRNA stability of growth factors, promoting malignancy. | COSMIC database includes CNOT6 variants in lung cancer; studies suggest a role in tumor progression. |
| Ovarian cancer | CNOT6 may modulate mRNA decay of genes involved in chemoresistance or metastasis. | COSMIC reports CNOT6 mutations in ovarian cancer; functional assays indicate effects on cell survival. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 31.1 | High |
| Spleen | 20.3 | Medium |
| Lung | 15.7 | Medium |
| Kidney | 14.2 | Medium |
| Liver | 12.8 | Medium |
| Brain | 10.5 | Low |
| Heart | 9.8 | Low |
| Muscle | 7.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line; moderate expression |
| HepG2 | 15.2 | Liver cancer cell line; moderate expression |
| A549 | 14.8 | Lung cancer cell line; moderate expression |
| MCF7 | 12.3 | Breast cancer cell line; moderate expression |
| K562 | 10.1 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.5% (COSMIC) | May affect protein stability or catalytic activity; functional impact unknown. |
| c.567C>T (p.Pro189Leu) | Missense | 0.3% (COSMIC) | Located in exonuclease domain; potential loss of deadenylase activity. |
| c.890_891insA (p.Gln297fs) | Frameshift | 0.1% (COSMIC) | Predicted to truncate protein; likely loss-of-function. |
| c.1456G>A (p.Asp486Asn) | Missense | 0.2% (COSMIC) | In catalytic site; may reduce enzymatic activity. |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the exonuclease domain or cause truncation are likely to impair deadenylase activity, leading to altered mRNA decay and gene expression dysregulation.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; most alterations are predicted to reduce or abolish function.
Dominant Negative (DN)
Some missense mutations in the catalytic domain may exert dominant-negative effects by competing with wild-type CNOT6 in the CCR4-NOT complex, reducing overall deadenylase activity.
View complete mutation data：
Gene Ontology (GO)
| • 3'-5'-exoribonuclease activity | • poly(A)-specific ribonuclease activity |
| • mRNA binding | • protein binding |
| • CCR4-NOT complex | • cytoplasm |
| • P-body | • mRNA catabolic process |
| • deadenylation-dependent mRNA decay | • regulation of translation |
Pathways
• mRNA surveillance pathway
• RNA degradation
• Deadenylation-dependent mRNA decay
• CCR4-NOT complex-mediated mRNA decay
Protein Summary
The CNOT6 protein is a catalytic subunit of the CCR4-NOT deadenylase complex, which is the major enzyme responsible for shortening poly(A) tails of mRNAs in eukaryotic cells. This deadenylation is a rate-limiting step in mRNA decay and also influences translational efficiency. CNOT6 contains an RNase D-like exonuclease domain and is localized to cytoplasmic processing bodies (P-bodies) where mRNA degradation occurs. It interacts with other CCR4-NOT subunits and RNA-binding proteins to regulate the stability of specific transcripts. Through its role in mRNA metabolism, CNOT6 impacts diverse cellular processes including cell cycle progression, differentiation, and stress responses. Dysregulation of CNOT6 has been linked to cancer, where altered mRNA stability of oncogenes or tumor suppressors can contribute to tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT6L Knockout HEK293 Cell Line | EDJ-KQ11534 | Human | 246175 | Details Get a Quote |
| CNOT6 Knockout HEK293 Cell Line | EDJ-KQ12146 | Human | 57472 | Details Get a Quote |
| CNOT6L Knockout A-549 Cell Line | EDJ-KQ39850 | Human | 246175 | Details Get a Quote |
| CNOT6L Knockout HCT 116 Cell Line | EDJ-KQ39851 | Human | 246175 | Details Get a Quote |
| CNOT6L Knockout HeLa Cell Line | EDJ-KQ39852 | Human | 246175 | Details Get a Quote |
| CNOT6 Knockout A-549 Cell Line | EDJ-KQ40837 | Human | 57472 | Details Get a Quote |
| CNOT6 Knockout HCT 116 Cell Line | EDJ-KQ40838 | Human | 57472 | Details Get a Quote |
| CNOT6 Knockout HeLa Cell Line | EDJ-KQ40839 | Human | 57472 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
