CNOT6L
protein-codingCCR4-NOT transcription complex subunit 6 like, the group of CCR4-NOT transcription complex
Gene summary
Predicted to enable 3'-5'-RNA exonuclease activity. Involved in positive regulation of cell population proliferation and positive regulation of cytoplasmic mRNA processing body assembly. Located in cytosol and nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~106.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CNOT6L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144571.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 37 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 41 | 1 | 0 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653172.2 | 12 | MANE Select | |
| Ensembl | ENSP00000424896.1 | 12 | MANE Select | |
| RefSeq | NP_001273719.1 | 12 | Standard | |
| RefSeq | NP_001351935.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA degradation - Homo sapiens (human)
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
- Metabolism of RNA
Biological Process
- nuclear-transcribed mRNA poly(A) tail shortening
- mRNA processing
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
- positive regulation of cell population proliferation
- positive regulation of cytoplasmic mRNA processing body assembly
Molecular Function
- poly(A)-specific ribonuclease activity
- protein binding
- metal ion binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- CCR4-NOT complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264903
- Coding exons
- 12
- Length
- 106229
- Individuals with no LoFs
- 124634
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 124639
- p
- 0.0000201
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.61 | 119 | 293 | 0.406 | 0.0000150 | 3635 |
| Missense (PolyPhen) | 21 | 125.05 | 0.16793 | 1570 | ||
| Synonymous | 0.721 | 100 | 110 | 0.912 | 0.00000579 | 1040 |
| Loss of Function | 4.49 | 2 | 27.3 | 0.0733 | 0.00000133 | 366 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in the deadenylation-dependent degradation of mRNAs through the 3'-UTR AU-rich element-mediated mechanism. Involved in deadenylation-dependent degradation of CDKN1B mRNA. Its mRNA deadenylase activity can be inhibited by TOB1. Mediates cell proliferation and cell survival and prevents cellular senescence. {ECO:0000269|PubMed:17452450, ECO:0000269|PubMed:21233283}.;
Intolerance Scores
- LoFtool
- 0.505
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |