CNOT6
protein-codingCCR4-NOT transcription complex subunit 6, the group of CCR4-NOT transcription complex
Gene summary
This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~84.0 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 CNOT6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001370472.1. 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 | 31 | 31 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 36 | 0 | 0 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001357401.1 | 11 | MANE Select | |
| Ensembl | ENSP00000261951.4 | 11 | MANE Select | |
| RefSeq | NP_001357402.1 | 11 | Standard | |
| RefSeq | NP_001357403.1 | 10 | 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
- regulation of translation
- 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
- RNA binding
- exoribonuclease activity
- poly(A)-specific ribonuclease activity
- protein binding
- metal ion binding
Cellular Component
- nucleus
- cytosol
- membrane
- CCR4-NOT complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393356
- Coding exons
- 11
- Length
- 83994
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125747
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 184 | 300 | 0.614 | 0.0000152 | 3660 |
| Missense (PolyPhen) | 29 | 77.562 | 0.37389 | 972 | ||
| Synonymous | 0.0120 | 112 | 112 | 0.999 | 0.00000591 | 1055 |
| Loss of Function | 3.31 | 8 | 26.4 | 0.304 | 0.00000129 | 339 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Poly(A) nuclease with 3'-5' RNase activity. 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. Involved in mRNA decay mediated by the major-protein- coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA. The increase of ligand-dependent ESR1-mediated transcription is much smaller, if any. Mediates cell proliferation and cell survival and prevents cellular senescence. {ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:20065043, ECO:0000269|PubMed:21233283}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- LoFtool
- 0.315
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.908
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |