CNOT4

protein-coding

CCR4-NOT transcription complex subunit 4, the group of CCR4-NOT transcription complex|Ring finger proteins|RNA binding motif containing

Gene summary

The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

Previous symbols:

NOT4

MANE transcript

NM_001190850.2

Inheritance

—

ClinVar variants

U:62

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr7:135,361,795-135,510,145

External References & Databases

Ensembl (ENSG00000080802)

Transcript & Mutation Effects

hg38 • Region Span ~148.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNOT4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001190850.2. 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			3 clinvar			3
missense			55 clinvar			55
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	62	0	0	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001190850.2	RefSeq	NP_001177779.1	11	MANE Select
ENST00000541284.6	Ensembl	ENSP00000445508.1	11	MANE Select
NM_001008225.3	RefSeq	NP_001008226.1	10	Standard
NM_001190847.2	RefSeq	NP_001177776.1	10	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

nuclear-transcribed mRNA poly(A) tail shortening
ubiquitin-dependent protein catabolic process
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
protein ubiquitination
regulation of megakaryocyte differentiation

Molecular Function

RNA binding
ubiquitin-protein transferase activity
protein binding
metal ion binding

Cellular Component

nucleus
cytosol
CCR4-NOT complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000541284
Coding exons: 11
Length: 148329
Individuals with no LoFs: 114657
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 114658
p: 0.00000436

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.49	207	405	0.512	0.0000217	4688
Missense (PolyPhen)		45	153.58	0.293		1801
Synonymous	0.348	147	152	0.964	0.00000867	1394
Loss of Function	5.17	1	33.1	0.0302	0.00000181	364

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)	0.0000094	0.0000094	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has E3 ubiquitin ligase activity, promoting ubiquitination and degradation of target proteins (PubMed:11823428, PubMed:22159038, PubMed:26575292). Involved in activation of the JAK/STAT pathway (PubMed:11823428, PubMed:22159038). Catalyzes ubiquitination of methylated RBM15 (PubMed:26575292). {ECO:0000269|PubMed:11823428, ECO:0000269|PubMed:22159038, ECO:0000269|PubMed:26575292}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.120
RVIS EVS: 0.04
RVIS percentile EVS: 57.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.912

Gene Damage Prediction

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