CNOT3

CCR4-NOT transcription complex subunit 3, the group of CCR4-NOT transcription complex

Basic information

Region (hg38): 19:54137749-54155681

Previous symbols: [ "NOT3" ]

Links

ENSG00000088038NCBI:4849OMIM:604910HGNC:7879Uniprot:O75175AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder with speech delay, autism, and dysmorphic faciesADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic31201375

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNOT3 gene.

  • 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
2
clinvar
45
clinvar
6
clinvar
53
missense
1
clinvar
7
clinvar
86
clinvar
10
clinvar
3
clinvar
107
nonsense
3
clinvar
1
clinvar
1
clinvar
5
start loss
0
frameshift
13
clinvar
1
clinvar
14
inframe indel
2
clinvar
3
clinvar
1
clinvar
6
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
2
7
10
19
non coding
2
clinvar
17
clinvar
10
clinvar
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)1683900
19-54142930-G-A Likely benign (Aug 01, 2024)1879454
19-54143007-C-T Benign/Likely benign (Feb 01, 2024)1971441
19-54143119-G-A Uncertain significance (May 27, 2022)3337923
19-54143150-C-T Likely benign (Jan 02, 2024)2867600
19-54143168-T-TG Inborn genetic diseases Pathogenic (Apr 28, 2023)2526437
19-54143186-G-A Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Likely pathogenic (May 29, 2020)976757
19-54143190-C-T Uncertain significance (May 01, 2022)2650415
19-54143199-A-G Benign (Sep 22, 2023)1971306
19-54143439-C-G Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Uncertain significance (May 14, 2021)2441996
19-54143444-C-T Likely benign (Dec 01, 2022)1879455
19-54143462-G-A Benign (Jan 22, 2024)1970984
19-54143485-C-G Inborn genetic diseases Uncertain significance (Jul 07, 2022)2299965
19-54143492-AAAG-A Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Likely pathogenic (Sep 17, 2021)1709920
19-54143496-AAGG-A Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Uncertain significance (Feb 21, 2022)1709182
19-54143501-G-T Uncertain significance (Mar 08, 2023)2843911
19-54143660-C-G CNOT3-related disorder Likely pathogenic (Sep 15, 2022)2629348
19-54143660-C-T Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Pathogenic (Jun 08, 2022)972977
19-54143665-G-A Likely benign (Jul 06, 2022)2126337
19-54143692-G-A CNOT3-related disorder Likely benign (Jan 23, 2024)2869833
19-54143697-A-C Uncertain significance (Jan 04, 2024)3367453
19-54143698-C-T CNOT3-related disorder Likely benign (Oct 01, 2023)1675759
19-54143704-C-A Likely benign (Dec 01, 2023)3026614
19-54143706-A-G Uncertain significance (May 22, 2023)3343586
19-54143732-C-A Intellectual developmental disorder with speech delay, autism, and dysmorphic facies Likely pathogenic (Oct 24, 2022)1713134

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CNOT3protein_codingprotein_codingENST00000406403 1717976
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.007.26e-7125661031256640.0000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.762304560.5040.00002864892
Missense in Polyphen31155.470.19941650
Synonymous-0.5632001901.050.00001351445
Loss of Function5.81039.30.000.00000205435

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003740.0000176
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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