CNOT1

CCR4-NOT transcription complex subunit 1, the group of CCR4-NOT transcription complex|Small nucleolar RNA protein coding host genes|Armadillo like helical domain containing|MIF4G domain containing proteins

Basic information

Region (hg38): 16:58519951-58629885

Previous symbols: [ "NOT1" ]

Links

ENSG00000125107 ∙ NCBI:23019 ∙ OMIM:604917 ∙ HGNC:7877 ∙ Uniprot:A5YKK6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• holoprosencephaly 12 with or without pancreatic agenesis (Strong), mode of inheritance: AD
• Vissers-Bodmer syndrome (Strong), mode of inheritance: AD
• holoprosencephaly 12 with or without pancreatic agenesis (Moderate), mode of inheritance: AD
• holoprosencephaly 12 with or without pancreatic agenesis (Strong), mode of inheritance: AD
• Vissers-Bodmer syndrome (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• holoprosencephaly 12 with or without pancreatic agenesis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Holoprosencephaly 12, with or without pancreatic agenesis	AD	Audiologic/Otolaryngologic; Endocrine	In addition to other findings, the condition has been described as sometimes involving congenital absence of the pancreas, which leads to medical interventions to manage early-onset insulin-dependent diabetes mellitus and the need for pancreatic enzyme replacement; In some individuals, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	28525974; 31006510; 32553196

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNOT1 gene.

• Vissers-Bodmer syndrome (3 variants)
• Neurodevelopmental delay (2 variants)
• Nuerodevelopment disorder (1 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNOT1 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	96	15	113
missense	2	1	205	11	3	222
nonsense	2	2	2			6
start loss						0
frameshift		7	3	2	2	14
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	3	2	1			6
splice region		1	13	21	6	41
non coding			1	58	70	129
Total	7	13	218	167	90

Variants in CNOT1

This is a list of pathogenic ClinVar variants found in the CNOT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-58520876-C-T			Benign (May 10, 2021)
16-58520968-C-G			Uncertain significance (Nov 18, 2023)
16-58521000-C-T			Likely benign (Nov 08, 2022)
16-58521021-G-A			Benign (Jun 29, 2023)
16-58521188-G-A			Likely benign (Oct 13, 2022)
16-58521215-A-T			Uncertain significance (Sep 04, 2023)
16-58521227-C-T			Likely benign (Mar 01, 2024)
16-58521252-T-C			Uncertain significance (Oct 19, 2023)
16-58521261-GTAA-G			Uncertain significance (Mar 22, 2023)
16-58521265-T-G			Likely pathogenic (Dec 13, 2022)
16-58521270-A-C			Uncertain significance (Feb 28, 2022)
16-58521271-G-C			Uncertain significance (Aug 17, 2023)
16-58521333-A-C			Likely benign (Dec 12, 2023)
16-58523305-G-GA			Benign (May 10, 2021)
16-58523363-C-T			Likely benign (Sep 21, 2023)
16-58523396-C-G			Likely benign (Jun 03, 2022)
16-58523434-T-C			Uncertain significance (May 20, 2022)
16-58523435-G-A			Likely benign (Oct 13, 2022)
16-58523438-G-A		CNOT1-related disorder	Benign (Jan 30, 2024)
16-58523468-C-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
16-58523496-T-G			Uncertain significance (Jan 15, 2023)
16-58523509-AT-A			Likely benign (Nov 15, 2022)
16-58525085-C-T			Benign (May 10, 2021)
16-58525168-G-A			Benign (Jan 18, 2024)
16-58525182-C-T			Uncertain significance (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNOT1	protein_coding	protein_coding	ENST00000317147	48	109936

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.56e-20	125740	0	4	125744	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	7.25	561	1.30e+3	0.433	0.0000691	15670
Missense in Polyphen		51	290.68	0.17545		3560
Synonymous	-0.514	470	456	1.03	0.0000240	4564
Loss of Function	10.3	1	125	0.00800	0.00000681	1440

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000176
Middle Eastern	0.0000546	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffolding 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. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of emryonic stem (ES) cell identity. {ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599}.
• 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: 0.135

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -1.9
• rvis_percentile_EVS: 1.97

Haploinsufficiency Scores

• pHI: 0.468
• hipred: Y
• hipred_score: 0.783
• ghis: 0.679

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cnot1
• 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); muscle phenotype

Zebrafish Information Network

• Gene name: cnot1
• Affected structure: anatomical system
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;nuclear-transcribed mRNA poly(A) tail shortening;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;multicellular organism development;positive regulation of cytoplasmic mRNA processing body assembly;negative regulation of translation;negative regulation of intracellular estrogen receptor signaling pathway;gene silencing by miRNA;negative regulation of retinoic acid receptor signaling pathway;positive regulation of nuclear-transcribed mRNA poly(A) tail shortening;positive regulation of mRNA catabolic process;RNA phosphodiester bond hydrolysis, exonucleolytic;positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;regulation of stem cell population maintenance
• Cellular component: P-body;extracellular space;nucleus;cytosol;membrane;CCR4-NOT complex
• Molecular function: RNA binding;poly(A)-specific ribonuclease activity;protein binding;protein domain specific binding;estrogen receptor binding;protein-containing complex scaffold activity;retinoic acid receptor binding;armadillo repeat domain binding