CNOT8
protein-codingCCR4-NOT transcription complex subunit 8, the group of CCR4-NOT transcription complex
Gene summary
Enables poly(A)-specific ribonuclease activity. Involved in miRNA-mediated gene silencing by mRNA destabilization and positive regulation of cell population proliferation. Located in nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Jul 2025]
- POP2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.2 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 CNOT8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001301073.2. 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 | 18 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 24 | 1 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001288002.1 | 6 | MANE Select | |
| Ensembl | ENSP00000285896.6 | 6 | MANE Select | |
| RefSeq | NP_001288003.1 | 5 | Standard | |
| RefSeq | NP_001288004.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cnot8 | Danio rerio | Structure: heart Quality: edematous abnormal |
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
- transcription, DNA-templated
- regulation of transcription, DNA-templated
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
- positive regulation of cell population proliferation
Molecular Function
- 3'-5'-exoribonuclease activity
- DNA-binding transcription factor activity
- RNA binding
- poly(A)-specific ribonuclease activity
- protein binding
Cellular Component
- P-body
- nucleus
- cytosol
- CCR4-NOT complex
- CCR4-NOT core complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000517876
- Coding exons
- 6
- Length
- 19241
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125744
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.16 | 78 | 153 | 0.508 | 0.00000738 | 1954 |
| Missense (PolyPhen) | 13 | 49.195 | 0.26425 | 685 | ||
| Synonymous | 0.601 | 48 | 53.6 | 0.896 | 0.00000245 | 523 |
| Loss of Function | 2.75 | 4 | 15.8 | 0.254 | 9.20e-7 | 178 |
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 | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000074 | 0.000070 | rare |
| South Asian | 0.000083 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT7. Catalytic component of the CCR4-NOT complex which is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity. {ECO:0000269|PubMed:12771185, ECO:0000269|PubMed:19605561, ECO:0000269|PubMed:20065043, ECO:0000269|PubMed:23236473}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.419
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |