CNOT8 (CCR4-NOT Transcription Complex Subunit 8) - A Key Regulator of Gene Expression and mRNA Decay
Explore the CNOT8 gene, its protein product, associated diseases, expression patterns, and functional roles in cellular processes.
Gene Information Card
| Symbol | CNOT8 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 8 |
| Gene Type | protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 9337 ncbi.nlm.nih.gov/gene/9337 |
| Ensembl ID | ENSG00000155508 |
| UniProt ID | Q9UFF9 |
| OMIM ID | 603282 |
| HGNC ID | 9199 |
| Aliases | POP2, CALIF, hPOP2, CCR4-NOT transcription complex subunit 8 |
Description
The CNOT8 gene encodes a catalytic subunit of the CCR4-NOT complex, a major regulator of mRNA metabolism. This complex is involved in mRNA deadenylation, which is the initial and rate-limiting step in mRNA decay, and also plays roles in transcription regulation, DNA damage response, and protein quality control. CNOT8, along with CNOT7, forms the catalytic core of the complex, providing poly(A)-specific 3'-5' exonuclease activity. It is a ubiquitously expressed protein essential for normal cellular function, and its dysregulation has been implicated in various cancers and developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Cancer (various types) | Dysregulation of CNOT8 expression can alter the stability of mRNAs encoding oncogenes or tumor suppressors, thereby affecting cell proliferation and survival. Its role in the CCR4-NOT complex is crucial for maintaining cellular homeostasis, and its aberrant expression can contribute to tumorigenesis. | COSMIC, PubMed |
| Developmental disorders | CNOT8 is essential for early embryonic development. Mutations or altered expression can disrupt gene expression programs critical for proper development, potentially leading to developmental abnormalities. | PubMed, OMIM |
| Potential role in neurological disorders | Given its role in mRNA decay, CNOT8 may influence synaptic plasticity and neuronal function. Altered expression could contribute to the pathophysiology of certain neurological conditions. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Bone marrow | 12.3 | Low |
| Spleen | 11.8 | Low |
| Lymph node | 11.5 | Low |
| Testis | 10.9 | Low |
| Brain (cerebellum) | 10.5 | Low |
| Liver | 9.8 | Low |
| Kidney | 9.5 | Low |
| Heart | 9.2 | Low |
| Lung | 8.9 | Low |
| Pancreas | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| K-562 (leukemia) | 14.2 | Moderate expression |
| HeLa (cervical cancer) | 13.5 | Moderate expression |
| A549 (lung cancer) | 12.8 | Moderate expression |
| MCF7 (breast cancer) | 12.1 | Moderate expression |
| HepG2 (liver cancer) | 11.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| Missense mutations (various) | Single nucleotide variants | Low (<1%) | May alter protein stability or catalytic activity, potentially affecting mRNA decay efficiency. |
| Copy number alterations | Amplification or deletion | Variable | Altered gene dosage can lead to overexpression or underexpression of CNOT8, disrupting cellular mRNA homeostasis. |
| Frameshift mutations | Insertion/deletion | Very rare | Likely result in a truncated, non-functional protein, leading to loss of CNOT8 function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CNOT8 are expected to impair the deadenylase activity of the CCR4-NOT complex, leading to stabilization of target mRNAs. This could result in aberrant expression of genes involved in cell cycle control, apoptosis, and differentiation, potentially contributing to tumorigenesis or developmental defects.
Gain of Function (GOF)
Gain-of-function mutations that increase CNOT8 catalytic activity are less well-characterized. They could theoretically lead to accelerated mRNA decay, reducing the expression of critical proteins and disrupting cellular processes. However, such mutations are not commonly reported.
Dominant Negative (DN)
A dominant-negative effect could occur if a mutant CNOT8 protein retains the ability to bind to the CCR4-NOT complex but lacks catalytic activity. This would inhibit the function of the wild-type complex, effectively reducing overall deadenylase activity and leading to similar consequences as loss-of-function mutations.
View complete mutation data：
Gene Ontology (GO)
| • 3'-5'-exoribonuclease activity | • poly(A) binding |
| • mRNA binding | • protein binding |
| • nucleus | • cytoplasm |
| • CCR4-NOT complex | • mRNA catabolic process |
| • nuclear-transcribed mRNA catabolic process | • deadenylation-dependent decay |
| • regulation of transcription by RNA polymerase II | • DNA damage response |
| • cell cycle |
Pathways
• mRNA surveillance pathway
• RNA degradation
• Deadenylation-dependent mRNA decay
• Cell cycle
• Gene expression
Protein Summary
The CNOT8 protein is a key catalytic subunit of the CCR4-NOT complex, functioning as a poly(A)-specific 3'-5' exonuclease. It is responsible for the deadenylation of mRNA poly(A) tails, a critical step in initiating mRNA decay. CNOT8 is involved in multiple cellular processes, including transcription regulation, mRNA quality control, and DNA damage response. It is a ubiquitously expressed protein essential for cellular homeostasis, and its dysregulation is linked to cancer and developmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT8 Knockout HEK293 Cell Line | EDJ-KQ6552 | Human | 9337 | Details Get a Quote |
| CNOT8 Knockout A-549 Cell Line | EDJ-KQ30748 | Human | 9337 | Details Get a Quote |
| CNOT8 Knockout HCT 116 Cell Line | EDJ-KQ30749 | Human | 9337 | Details Get a Quote |
| CNOT8 Knockout HeLa Cell Line | EDJ-KQ30750 | Human | 9337 | Details Get a Quote |
