CNOT2
CCR4-NOT transcription complex subunit 2, the group of CCR4-NOT transcription complex
Basic information
Region (hg38): 12:70243002-70354993
Previous symbols: [ "NOT2" ]
Links
Phenotypes
GenCC
Source:
- intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies (Strong), mode of inheritance: AD
- intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal; Neurologic | 31145527; 31512373 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNOT2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 28 | 31 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 2 | 2 | ||||
| non coding | 2 | |||||
| Total | 2 | 1 | 30 | 4 | 0 |
Variants in CNOT2
This is a list of pathogenic ClinVar variants found in the CNOT2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CNOT2 | protein_coding | protein_coding | ENST00000229195 | 15 | 112000 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000187 | 124567 | 0 | 2 | 124569 | 0.00000803 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.65 | 119 | 295 | 0.403 | 0.0000148 | 3566 |
| Missense in Polyphen | 17 | 77.754 | 0.21864 | 986 | ||
| Synonymous | 0.942 | 92 | 104 | 0.883 | 0.00000546 | 999 |
| Loss of Function | 5.03 | 2 | 33.3 | 0.0600 | 0.00000181 | 384 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000177 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: 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. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of emryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}.;
- Pathway
- RNA degradation - Homo sapiens (human);Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Metabolism of RNA;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain;TP53 Regulates Transcription of Cell Cycle Genes;Transcriptional Regulation by TP53;Deadenylation of mRNA;Deadenylation-dependent mRNA decay
(Consensus)
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- loftool
- rvis_EVS
- -0.12
- rvis_percentile_EVS
- 44.89
Haploinsufficiency Scores
- pHI
- 0.287
- hipred
- Y
- hipred_score
- 0.739
- ghis
- 0.616
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cnot2
- Phenotype
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;nuclear-transcribed mRNA poly(A) tail shortening;trophectodermal cell differentiation;regulation of transcription by RNA polymerase II;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;positive regulation of cytoplasmic mRNA processing body assembly;negative regulation of translation;gene silencing by RNA;negative regulation of intracellular estrogen receptor signaling pathway;RNA phosphodiester bond hydrolysis, exonucleolytic;regulation of stem cell population maintenance
- Cellular component
- P-body;nucleus;cytoplasm;cytosol;plasma membrane;membrane;CCR4-NOT complex;CCR4-NOT core complex
- Molecular function
- RNA polymerase II transcription corepressor binding;transcription coregulator activity;poly(A)-specific ribonuclease activity;protein binding