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

ENSG00000111596 ∙ NCBI:4848 ∙ OMIM:604909 ∙ HGNC:7878 ∙ Uniprot:Q9NZN8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the CNOT2 gene.

• Inborn_genetic_diseases (29 variants)
• not_provided (22 variants)
• Intellectual_developmental_disorder_with_nasal_speech,_dysmorphic_facies,_and_variable_skeletal_anomalies (5 variants)
• CNOT2-related_disorder (3 variants)
• Normal_pregnancy (2 variants)
• ADNP-related_multiple_congenital_anomalies_-_intellectual_disability_-_autism_spectrum_disorder (2 variants)
• Neurodevelopmental_disorder (1 variants)
• not_specified (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. These statistics are base on transcript: NM_000014515.7. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense	1		44	5		50
nonsense	2					2
start loss						0
frameshift	1	2				3
splice donor/acceptor (+/-2bp)		1	1			2
Total	4	3	45	6	0

GnomAD

Source: gnomAD

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: 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. 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

• 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

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