CNOT12 (CCR4-NOT Transcription Complex Subunit 12)
A core component of the CCR4-NOT deadenylase complex involved in mRNA degradation and gene expression regulation.
Gene Information Card
| Symbol | CNOT12 |
|---|---|
| Full Name | CCR4-NOT transcription complex subunit 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 23003 ncbi.nlm.nih.gov/gene/23003 |
| Ensembl ID | ENSG00000100360 |
| UniProt ID | Q9H0A0 |
| OMIM ID | 616910 |
| HGNC ID | 29293 |
| Aliases | NOT12, CCR4b, C20orf7 (historical) |
Description
CNOT12 encodes a catalytic subunit of the CCR4-NOT deadenylase complex, which shortens mRNA poly(A) tails and thereby regulates mRNA stability and translation. It is involved in gene expression control, cell proliferation, and differentiation. CNOT12 is broadly expressed and its dysregulation has been implicated in various cancers and developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Altered CNOT12 expression may affect mRNA turnover of oncogenes/tumor suppressors, but specific mechanisms are not fully defined. | COSMIC lists CNOT12 mutations in multiple cancer types; ClinVar has limited clinical assertions. |
| Developmental disorders | Potential impact on gene expression programs during embryogenesis; no definitive monogenic disease established. | OMIM notes CNOT12 as a candidate for intellectual disability based on a single report (not yet confirmed). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Kidney | 8.9 | Low |
| Liver | 7.2 | Low |
| Brain | 6.5 | Low |
| Heart | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | 10.5 | Chronic myelogenous leukemia cell line |
| HeLa | 8.3 | Cervical adenocarcinoma |
| A549 | 7.9 | Lung carcinoma |
| HepG2 | 6.8 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Ter) | Nonsense | Rare (MAF <0.01%) | Predicted loss-of-function; may reduce deadenylase activity. |
| c.1544A>G (p.Tyr515Cys) | Missense | Rare (MAF <0.01%) | Uncertain significance; possibly affects protein stability. |
| c.2011G>A (p.Val671Met) | Missense | Rare (MAF <0.01%) | Uncertain significance; no functional data. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and may impair mRNA deadenylation, leading to altered gene expression. No germline pathogenic variants have been established.
Gain of Function (GOF)
No evidence for gain-of-function mutations in CNOT12.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • mRNA deadenylase activity | • poly(A)-specific ribonuclease activity |
| • CCR4-NOT complex | • mRNA catabolic process |
| • regulation of gene expression |
Pathways
• mRNA degradation (deadenylation-dependent)
• CCR4-NOT complex pathway
Protein Summary
CNOT12 is a 657-amino-acid protein that contains a DEDD-like nuclease domain and functions as a 3'-5' exoribonuclease. It is a catalytic component of the CCR4-NOT complex, which is the major mRNA deadenylase in eukaryotic cells. The protein interacts with other complex subunits and is involved in shortening poly(A) tails, thereby influencing mRNA stability and translational efficiency. CNOT12 is ubiquitously expressed but shows higher levels in testis and certain cancer cell lines.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNOT12 Knockout HEK293 Cell Line | EDJ-KQ2920 | Human | 85456 | 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 |
