CNOT3
Basic information
Region (hg38): 19:54137749-54155681
Previous symbols: [ "NOT3" ]
Links
Phenotypes
GenCC
Source:
- intellectual developmental disorder with speech delay, autism, and dysmorphic facies (Strong), mode of inheritance: AD
- complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
- intellectual developmental disorder with speech delay, autism, and dysmorphic facies (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | 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 | 31201375 |
ClinVar
This is a list of variants' phenotypes submitted to
- Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (10 variants)
- not provided (7 variants)
- Inborn genetic diseases (3 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNOT3 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 | 45 | 53 | ||||
missense | 86 | 10 | 107 | |||
nonsense | 5 | |||||
start loss | 0 | |||||
frameshift | 13 | 14 | ||||
inframe indel | 6 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 2 | 7 | 10 | 19 | ||
non coding | 17 | 10 | 29 | |||
Total | 18 | 11 | 94 | 72 | 20 |
Variants in CNOT3
This is a list of pathogenic ClinVar variants found in the CNOT3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
19-54142920-T-G | Uncertain significance (Oct 27, 2021) | |||
19-54142930-G-A | Likely benign (Aug 01, 2024) | |||
19-54143007-C-T | Benign/Likely benign (Feb 01, 2024) | |||
19-54143119-G-A | Uncertain significance (May 27, 2022) | |||
19-54143150-C-T | Likely benign (Jan 02, 2024) | |||
19-54143168-T-TG | Inborn genetic diseases | Pathogenic (Apr 28, 2023) | ||
19-54143186-G-A | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Likely pathogenic (May 29, 2020) | ||
19-54143190-C-T | Uncertain significance (May 01, 2022) | |||
19-54143199-A-G | Benign (Sep 22, 2023) | |||
19-54143439-C-G | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Uncertain significance (May 14, 2021) | ||
19-54143444-C-T | Likely benign (Dec 01, 2022) | |||
19-54143462-G-A | Benign (Jan 22, 2024) | |||
19-54143485-C-G | Inborn genetic diseases | Uncertain significance (Jul 07, 2022) | ||
19-54143492-AAAG-A | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Likely pathogenic (Sep 17, 2021) | ||
19-54143496-AAGG-A | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Uncertain significance (Feb 21, 2022) | ||
19-54143501-G-T | Uncertain significance (Mar 08, 2023) | |||
19-54143660-C-G | CNOT3-related disorder | Likely pathogenic (Sep 15, 2022) | ||
19-54143660-C-T | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Pathogenic (Jun 08, 2022) | ||
19-54143665-G-A | Likely benign (Jul 06, 2022) | |||
19-54143692-G-A | CNOT3-related disorder | Likely benign (Jan 23, 2024) | ||
19-54143697-A-C | Uncertain significance (Jan 04, 2024) | |||
19-54143698-C-T | CNOT3-related disorder | Likely benign (Oct 01, 2023) | ||
19-54143704-C-A | Likely benign (Dec 01, 2023) | |||
19-54143706-A-G | Uncertain significance (May 22, 2023) | |||
19-54143732-C-A | Intellectual developmental disorder with speech delay, autism, and dysmorphic facies | Likely pathogenic (Oct 24, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
CNOT3 | protein_coding | protein_coding | ENST00000406403 | 17 | 17976 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.00 | 7.26e-7 | 125661 | 0 | 3 | 125664 | 0.0000119 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 3.76 | 230 | 456 | 0.504 | 0.0000286 | 4892 |
Missense in Polyphen | 31 | 155.47 | 0.1994 | 1650 | ||
Synonymous | -0.563 | 200 | 190 | 1.05 | 0.0000135 | 1445 |
Loss of Function | 5.81 | 0 | 39.3 | 0.00 | 0.00000205 | 435 |
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) | 0.0000374 | 0.0000176 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.0000327 | 0.0000327 |
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. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:22342980, 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
- 0.102
Intolerance Scores
- loftool
- 0.408
- rvis_EVS
- -0.6
- rvis_percentile_EVS
- 18.14
Haploinsufficiency Scores
- pHI
- 0.731
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.518
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.948
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cnot3
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; immune system phenotype;
Gene ontology
- Biological process
- nuclear-transcribed mRNA poly(A) tail shortening;trophectodermal cell differentiation;regulation of transcription, DNA-templated;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;negative regulation of translation;gene silencing by RNA;positive regulation of cold-induced thermogenesis;regulation of stem cell population maintenance
- Cellular component
- P-body;nucleus;cytosol;CCR4-NOT complex;CCR4-NOT core complex
- Molecular function
- protein binding