CNOT1: CCR4-NOT Transcription Complex Subunit 1
A master regulator of mRNA deadenylation and gene expression, implicated in developmental disorders and cancer
Gene Information Card
| Symbol | CNOT1 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | 29899 ncbi.nlm.nih.gov/gene/29899 |
| Ensembl ID | ENSG00000125124 |
| UniProt ID | A5YKK6 |
| OMIM ID | 604917 |
| HGNC ID | 14008 |
| Aliases | CDC39, NOT1, NOT1H, hNOT1 |
Description
CNOT1 encodes the largest subunit of the CCR4-NOT complex, a major regulator of mRNA deadenylation and turnover. The complex controls gene expression by shortening poly(A) tails, thereby influencing mRNA stability and translation. CNOT1 serves as a scaffold for the assembly of other subunits and is essential for embryonic development. Mutations in CNOT1 are associated with neurodevelopmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and variable intellectual disability | Loss-of-function mutations in CNOT1 disrupt mRNA deadenylation, leading to altered gene expression profiles critical for neuronal development. | ClinVar, OMIM |
| Holoprosencephaly | CNOT1 mutations impair the CCR4-NOT complex function, affecting signaling pathways required for forebrain development. | ClinVar, OMIM |
| Breast cancer | CNOT1 overexpression or mutation alters mRNA stability of oncogenes and tumor suppressors, promoting cell proliferation. | COSMIC, NCBI Gene |
| Colorectal cancer | CNOT1 dysregulation affects the expression of genes involved in cell cycle and apoptosis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain cortex | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 8.5 | Low |
| Kidney | 10.1 | Medium |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.5 | Embryonic kidney cells |
| HeLa | 12.3 | Cervical cancer cells |
| K562 | 9.8 | Leukemia cells |
| HepG2 | 11.0 | Liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; associated with neurodevelopmental disorder |
| c.5678A>G (p.Tyr1893Cys) | Missense | <0.01% | Unknown significance; reported in cancer |
| c.2345_2346del (p.Leu782fs) | Frameshift | <0.05% | Loss of function; linked to holoprosencephaly |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the scaffold function of CNOT1, leading to impaired mRNA deadenylation and developmental defects.
Gain of Function (GOF)
Not well characterized; some missense mutations may enhance CNOT1 stability or interaction with other complex subunits, potentially contributing to oncogenesis.
Dominant Negative (DN)
Certain missense mutations may produce a protein that interferes with wild-type CNOT1 function, reducing complex activity and causing dominant phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • mRNA deadenylation | • regulation of transcription by RNA polymerase II |
| • CCR4-NOT complex | • poly(A) RNA binding |
| • protein binding |
Pathways
• mRNA surveillance pathway
• RNA degradation
• Cell cycle
Protein Summary
CNOT1 is a 2376-amino acid protein that acts as a scaffold for the CCR4-NOT complex. It contains multiple domains for interaction with other subunits and RNA. The protein is essential for deadenylation-dependent mRNA decay and also participates in transcriptional regulation. Its expression is ubiquitous, with higher levels in testis and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT12 Knockout HEK293 Cell Line | EDJ-KQ2920 | Human | 85456 | Details Get a Quote |
| CNOT10 Knockout HEK293 Cell Line | EDJ-KQ8292 | Human | 25904 | Details Get a Quote |
| CNOT11 Knockout HEK293 Cell Line | EDJ-KQ12964 | Human | 55571 | Details Get a Quote |
| CNOT11 Knockout A-549 Cell Line | EDJ-KQ40933 | Human | 55571 | Details Get a Quote |
| CNOT11 Knockout HCT 116 Cell Line | EDJ-KQ42179 | Human | 55571 | Details Get a Quote |
| CNOT11 Knockout HeLa Cell Line | EDJ-KQ42180 | Human | 55571 | Details Get a Quote |
| CNOT12 Knockout A-549 Cell Line | EDJ-KQ25393 | Human | 85456 | Details Get a Quote |
| CNOT12 Knockout HCT 116 Cell Line | EDJ-KQ25394 | Human | 85456 | Details Get a Quote |
| CNOT12 Knockout HeLa Cell Line | EDJ-KQ25395 | Human | 85456 | Details Get a Quote |
| CNOT10 Knockout A-549 Cell Line | EDJ-KQ34253 | Human | 25904 | Details Get a Quote |
| CNOT10 Knockout HCT 116 Cell Line | EDJ-KQ34254 | Human | 25904 | Details Get a Quote |
| CNOT10 Knockout HeLa Cell Line | EDJ-KQ34255 | Human | 25904 | Details Get a Quote |
