CNOT3 (CCR4-NOT transcription complex subunit 3)

Gene

• Entrez ID: 4849
• Gene name: CCR4-NOT transcription complex subunit 3
• Gene symbol: CNOT3
• Synonyms (NCBI Gene): IDDSADF, LENG2, NOT3, NOT3H
• Chromosome: 19
• Chromosome location: 19q13.42

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs753475896	C>-,CC,CCC	Uncertain-significance, pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT051783	hsa-let-7c-5p	CLASH	23622248
MIRT039544	hsa-miR-652-3p	CLASH	23622248
MIRT038618	hsa-miR-185-3p	CLASH	23622248
MIRT900388	hsa-miR-1343	CLIP-seq
MIRT900389	hsa-miR-2115	CLIP-seq
MIRT900390	hsa-miR-3150a-3p	CLIP-seq
MIRT900391	hsa-miR-3175	CLIP-seq
MIRT900392	hsa-miR-3192	CLIP-seq
MIRT900393	hsa-miR-4313	CLIP-seq
MIRT900394	hsa-miR-4667-5p	CLIP-seq
MIRT900395	hsa-miR-4700-5p	CLIP-seq
MIRT900396	hsa-miR-4728-5p	CLIP-seq
MIRT900397	hsa-miR-4779	CLIP-seq
MIRT900398	hsa-miR-486-3p	CLIP-seq
MIRT900399	hsa-miR-516a-3p	CLIP-seq
MIRT900400	hsa-miR-765	CLIP-seq
MIRT900401	hsa-miR-939	CLIP-seq
MIRT900388	hsa-miR-1343	CLIP-seq
MIRT900389	hsa-miR-2115	CLIP-seq
MIRT900392	hsa-miR-3192	CLIP-seq
MIRT2202759	hsa-miR-4525	CLIP-seq
MIRT2202760	hsa-miR-4716-3p	CLIP-seq
MIRT900397	hsa-miR-4779	CLIP-seq
MIRT900398	hsa-miR-486-3p	CLIP-seq
MIRT900399	hsa-miR-516a-3p	CLIP-seq
MIRT900400	hsa-miR-765	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000289	Process	Nuclear-transcribed mRNA poly(A) tail shortening	IBA
GO:0000289	Process	Nuclear-transcribed mRNA poly(A) tail shortening	NAS	31320642
GO:0000932	Component	P-body	IBA
GO:0000932	Component	P-body	IEA
GO:0000932	Component	P-body	ISS
GO:0001829	Process	Trophectodermal cell differentiation	IEA
GO:0005515	Function	Protein binding	IPI	10637334, 12207886, 16189514, 16778766, 17452450, 18377426, 20211142, 21981923, 21984185, 24736845, 26496610, 28514442, 31515488, 32296183, 32814053, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006417	Process	Regulation of translation	IEA
GO:0030014	Component	CCR4-NOT complex	IDA	19558367
GO:0030014	Component	CCR4-NOT complex	NAS	19558367
GO:0030015	Component	CCR4-NOT core complex	IBA
GO:0030015	Component	CCR4-NOT core complex	IEA
GO:0031047	Process	Regulatory ncRNA-mediated gene silencing	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	28032897
GO:2000036	Process	Regulation of stem cell population maintenance	IBA
GO:2000036	Process	Regulation of stem cell population maintenance	IEA
GO:2000036	Process	Regulation of stem cell population maintenance	IMP	22367759

Other IDs

• MIM: 604910
• HGNC: 7879
• e!Ensembl: ENSG00000088038

Protein

• UniProt ID: O75175
• Protein name: CCR4-NOT transcription complex subunit 3 (CCR4-associated factor 3) (Leukocyte receptor cluster member 2)
• Protein 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 initiati
• PDB: 4C0D, 4C0G, 5FU6, 5FU7, 9C3H, 9C3I
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04065	Not3	3 → 232	Not1 N-terminal domain, CCR4-Not complex component	Family
  PF04153	NOT2_3_5	620 → 747	NOT2 / NOT3 / NOT5 family	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. Highly expressed in brain, heart, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes. {ECO:0000269|PubMed:10637334}.
• Sequence:

  MADKRKLQGEIDRCLKKVSEGVEQFEDIWQKLHNAANANQKEKYEADLKKEIKKLQRLRD
  QIKTWVASNEIKDKRQLIDNRKLIETQMERFKVVERETKTKAYSKEGLGLAQKVDPAQKE
  KEEVGQWLTNTIDTLNMQVDQFESEVESLSVQTRKKKGDKDKQDRIEGLKRHIEKHRYHV
  RMLETILRMLDNDSILVDAIRKIKDDVEYYVDSSQDPDFEENEFLYDDLDLEDIPQALVA
  TSPPSHSHMEDEIFNQSSSTPTSTTSSSPIPPSPANCTTENSEDDKKRGRSTDSEVSQSP
  AKNGSKPVHSNQHPQSPAVPPTYPSGPPPAASALSTTPGNNGVPAPAAPPSALGPKASPA
  PSHNSGTPAPYAQAVAPPAPSGPSTTQPRPPSVQPSGGGGGGSGGGGSSSSSNSSAGGGA
  GKQNGATSYSSVVADSPAEVALSSSGGNNASSQALGPPSGPHNPPPSTSKEPSAAAPTGA
  GGVAPGSGNNSGGPSLLVPLPVNPPSSPTPSFSDAKAAGALLNGPPQFSTAPEIKAPEPL
  SSLKSMAERAAISSGIEDPVPTLHLTERDIILSSTSAPPASAQPPLQLSEVNIPLSLGVC
  PLGPVPLTKEQLYQQAMEEAAWHHMPHPSDSERIRQYLPRNPCPTPPYHHQMPPPHSDTV
  EFYQRLSTETLFFIFYYLEGTKAQYLAAKALKKQSWRFHTKYMMWFQRHEEPKTITDEFE
  QGTYIYFDYEKWGQRKKEGFTFEYRYLEDRDLQ

• Sequence length: 753

Pathways

KEGG:

RNA degradation

Reactome:

Deadenylation of mRNA
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
CNOT3-associated disorder	Pathogenic	rs2075273330	RCV005622169	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CNOT3-related disorder	Likely pathogenic; Pathogenic	rs2074547544, rs753475896	RCV003414162 RCV004751757	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual developmental disorder with speech delay, autism, and dysmorphic facies	Pathogenic; Likely pathogenic	rs2146638782, rs2146758722, rs2146646096, rs2518137990, rs2075273330, rs2517256882, rs2517294280, rs2514436908, rs2514116435, rs2514644148, rs2517525537, rs2518058484, rs2517611666, rs1213228037, rs2518542445, rs753475896, rs1600471396, rs1600501018, rs1600504088, rs1600514073, rs2074547544, rs2074521998	RCV001706941 RCV002249370 RCV002251052 RCV002286442 RCV002286457 RCV002290262 RCV002302842 RCV002472291 RCV002470305 RCV003232958 RCV003314128 RCV003315270 RCV004809995 RCV003988703 RCV003989449 RCV000856720 RCV000856721 RCV000856722 RCV000856723 RCV000856724 RCV002286829 RCV001254143	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Moyamoya angiopathy with developmental delay	Likely pathogenic	rs2074638284, rs2074949880	RCV001261733 RCV001261734	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Autism spectrum disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Complex neurodevelopmental disorder	Conflicting classifications of pathogenicity	ClinVar ClinGen, GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual disability	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult T-Cell Lymphoma/Leukemia	T-Cell Lymphoma/Leukemia	BEFREE	16865235		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	31630801		★☆☆☆☆ Found in Text Mining only
Ankylosing spondylitis	Ankylosing Spondylitis	BEFREE	22294640		★☆☆☆☆ Found in Text Mining only
Arterial Occlusive Diseases	Arterial occlusive disease	Pubtator	31474762	Stimulate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	34208845	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	28358798		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	31177396		★☆☆☆☆ Found in Text Mining only
Carcinoma Small Cell	Small cell carcinoma	Pubtator	31201375	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Disease	Chronic disease	Pubtator	34208845	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	27899379		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	20371351, 29438013		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	31201375		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	31201375, 31474762	Associate	★☆☆☆☆ Found in Text Mining only
Dowling Degos Disease	Dowling degos disease	Pubtator	31201375	Associate	★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	10637334, 11696541, 12215531, 17273961, 20371351, 21897366, 22495309, 23280189, 24267886, 26637982, 26821858, 27824329, 28135719, 28263302		★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	31474762	Associate	★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	20371351, 29438013		★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	Pubtator	40603987	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	31201375		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Intellectual developmental disorder	Pubtator	31201375, 31474762	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Keratoconus	Keratoconus	Pubtator	36811882	Associate	★☆☆☆☆ Found in Text Mining only
Language Development Disorders	Language development disorders	Pubtator	34208845	Associate	★☆☆☆☆ Found in Text Mining only
Lipodystrophy	Lipodystrophy	BEFREE	28032897		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	28358798		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	31177396		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	29610475, 29662167		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27899379, 28588606, 30531840, 31177396		★☆☆☆☆ Found in Text Mining only
Mental Retardation Autosomal Recessive 7	Intellectual developmental disorder	Pubtator	34208845	Associate	★☆☆☆☆ Found in Text Mining only
Moyamoya Disease	Moyamoya Disease	BEFREE	31474762		★☆☆☆☆ Found in Text Mining only
Moyamoya disease 1	Moyamoya disease	Pubtator	31474762	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	30809292	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23263491, 27899379, 30144809, 30531840		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	31201375		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	30531840		★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	GWASCAT_DG	30450575		★☆☆☆☆ Found in Text Mining only
Precursor T-cell acute lymphoblastic leukemia	Lymphoblastic Leukemia	Orphanet			★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	23263491, 27151989, 30144809, 30531840		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	CTD_human_DG	23263491		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	ORPHANET_DG	23263491		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	CGI_DG			★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	29610475, 29662167		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal Degeneration	Retinal degeneration	Pubtator	23144630	Inhibit	★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	23144630, 24116917		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	23144630, 24116917, 36338669	Associate	★☆☆☆☆ Found in Text Mining only