CNOT2
protein-codingCCR4-NOT transcription complex subunit 2, the group of CCR4-NOT transcription complex
Gene summary
This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]
- NOT2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~112.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0032832
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0032832
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CNOT2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014515.7. 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 | 5 | 5 | ||||
| missense | 54 | 6 | 60 | |||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 1 | 6 | ||
| splice donor/acceptor (+/-2bp) | 1 | 6 | 7 | |||
| Total | 3 | 6 | 61 | 11 | 0 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055330.1 | 15 | MANE Select | |
| Ensembl | ENSP00000229195.3 | 15 | MANE Select | |
| RefSeq | NP_001186231.1 | 15 | Standard | |
| RefSeq | NP_001186232.1 | 15 | 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
- 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
Molecular Function
- RNA polymerase II transcription corepressor binding
- transcription coregulator activity
- poly(A)-specific ribonuclease activity
- protein binding
Cellular Component
- P-body
- nucleus
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000229195
- Coding exons
- 15
- Length
- 112000
- Individuals with no LoFs
- 124567
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124569
- p
- 0.00000803
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.65 | 119 | 295 | 0.403 | 0.0000148 | 3566 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- 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 |