CNOT4: CCR4-NOT Transcription Complex Subunit 4
A key regulator of mRNA deadenylation and gene expression, implicated in developmental disorders and cancer.
Gene Information Card
| Symbol | CNOT4 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q33 |
| NCBI Gene ID | 4850 ncbi.nlm.nih.gov/gene/4850 |
| Ensembl ID | ENSG00000106344 |
| UniProt ID | O95628 |
| OMIM ID | 604913 |
| HGNC ID | 7880 |
| Aliases | NOT4, CLONE249, CCR4-associated factor 4 |
Description
CNOT4 encodes a subunit of the CCR4-NOT complex, a major regulator of mRNA deadenylation and turnover. The protein possesses E3 ubiquitin ligase activity and is involved in transcription regulation, RNA decay, and DNA damage response. CNOT4 is essential for normal development and its dysregulation is linked to neurodevelopmental disorders and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and variable intellectual disability | Loss-of-function mutations impair mRNA deadenylation, disrupting neuronal gene expression programs. | ClinVar, OMIM |
| Breast cancer | CNOT4 overexpression correlates with poor prognosis; may promote cell proliferation via altered mRNA stability. | COSMIC, NCBI |
| Colorectal cancer | Somatic mutations and copy number alterations affect CNOT4, potentially influencing Wnt/β-catenin signaling. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Brain | 8.2 | Medium |
| Heart | 6.1 | Medium |
| Liver | 4.3 | Low |
| Kidney | 5.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells; high expression |
| HeLa | 7.8 | Cervical cancer cells; moderate expression |
| MCF7 | 9.3 | Breast cancer cells; elevated expression |
| HepG2 | 4.5 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon; predicted loss of function |
| c.742C>T (p.Arg248*) | nonsense | <0.01% | Premature stop; loss of function |
| c.1054G>A (p.Glu352Lys) | missense | 0.02% | Alters ubiquitin ligase activity; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance E3 ligase activity.
Dominant Negative (DN)
Not reported for CNOT4.
View complete mutation data：
Gene Ontology (GO)
| • mRNA deadenylation (GO:0000289) | • ubiquitin protein ligase activity (GO:0061630) |
| • transcription coactivator activity (GO:0003713) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • CCR4-NOT complex (GO:0016283) |
Pathways
• mRNA surveillance pathway (KEGG: hsa03015)
• RNA degradation (KEGG: hsa03018)
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
Protein Summary
CNOT4 is a 575-amino acid protein containing a RING finger domain responsible for E3 ubiquitin ligase activity and a NOT-box domain for interaction with the CCR4-NOT complex. It mediates ubiquitination of target proteins, including histones and transcription factors, thereby influencing chromatin dynamics and gene expression. The protein is predominantly nuclear but shuttles to the cytoplasm.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT4 Knockout HEK293 Cell Line | EDJ-KQ5356 | Human | 4850 | Details Get a Quote |
| CNOT4 Knockout A-549 Cell Line | EDJ-KQ27234 | Human | 4850 | Details Get a Quote |
| CNOT4 Knockout HCT 116 Cell Line | EDJ-KQ28466 | Human | 4850 | Details Get a Quote |
| CNOT4 Knockout HeLa Cell Line | EDJ-KQ28467 | Human | 4850 | Details Get a Quote |
