CNOT1

Summary

CNOT1 (CCR4-NOT transcription complex subunit 1, HGNC:7877) is a protein-coding gene on chromosome 16q21, encoding CCR4-NOT transcription complex subunit 1 (A5YKK6). 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 transcr…. It is a selective cancer dependency (DepMap: 72.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Enables armadillo repeat domain binding activity; molecular adaptor activity; and nuclear receptor binding activity. Contributes to poly(A)-specific ribonuclease activity. Involved in several processes, including negative regulation of intracellular signal transduction; positive regulation of cytoplasmic mRNA processing body assembly; and regulation of gene expression. Located in P-body. Part of CCR4-NOT complex. Implicated in Vissers-Bodmer syndrome and holoprosencephaly 12.

Source: NCBI Gene 23019 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 111 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 1,019 total — 19 pathogenic, 34 likely-pathogenic (top 3% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 13 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 18 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 23
• Cancer dependency (DepMap): dependent in 72.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.06 (highly constrained)
• MANE Select transcript: NM_016284
• Interaction hub: 2,562 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7877
Approved symbol	CNOT1
Name	CCR4-NOT transcription complex subunit 1
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	CDC39, NOT1H, KIAA1007, AD-005
Ensembl gene	ENSG00000125107
Ensembl biotype	protein_coding
OMIM	604917
Entrez	23019

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 20 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000317147

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 4, TSL 3: 7, TSL 4: 4, TSL 5: 3

ENST00000317147, ENST00000441024, ENST00000562046, ENST00000563130, ENST00000563283, ENST00000564557, ENST00000565605, ENST00000565697, ENST00000566240, ENST00000567133, ENST00000567188, ENST00000567285, ENST00000568158, ENST00000568917, ENST00000569020, ENST00000569240, ENST00000569263, ENST00000569732, ENST00000569882, ENST00000569916, ENST00000569924, ENST00000570139, ENST00000880845, ENST00000938267, ENST00000938268, ENST00000938269, ENST00000938270, ENST00000981087, ENST00000981088, ENST00001041599, ENST00001065137, ENST00001107859, ENST00001135596

RefSeq mRNA: 3 — MANE Select: NM_016284 NM_001265612, NM_016284, NM_206999

CCDS: CCDS10799, CCDS45501, CCDS58468

Canonical transcript exons

ENST00000317147 — 49 exons

Exon	Start	End
ENSE00001598351	58553782	58553860
ENSE00001599392	58536989	58537220
ENSE00001602076	58545361	58545491
ENSE00001602293	58582793	58582903
ENSE00001617083	58541501	58541620
ENSE00001622849	58580633	58580760
ENSE00001628119	58587345	58587413
ENSE00001632482	58558473	58558674
ENSE00001632878	58587780	58587878
ENSE00001634130	58539768	58539959
ENSE00001634833	58549719	58549898
ENSE00001636717	58581345	58581515
ENSE00001645392	58532232	58532395
ENSE00001654150	58546321	58546498
ENSE00001658140	58576463	58576582
ENSE00001662924	58551589	58551819
ENSE00001663046	58546672	58546749
ENSE00001663070	58542231	58542335
ENSE00001675588	58547566	58547682
ENSE00001691499	58537891	58538060
ENSE00001697515	58583056	58583182
ENSE00001700821	58585338	58585506
ENSE00001716391	58534147	58534395
ENSE00001748964	58574609	58574760
ENSE00001760333	58560212	58560362
ENSE00001764145	58587201	58587255
ENSE00001769368	58578699	58578939
ENSE00001770039	58547186	58547296
ENSE00001775315	58588799	58588906
ENSE00001782694	58586545	58586748
ENSE00001799281	58556847	58556993
ENSE00001891750	58519951	58521036
ENSE00002576463	58629728	58629826
ENSE00002719835	58599236	58599511
ENSE00003477453	58542428	58542568
ENSE00003512089	58551132	58551272
ENSE00003513446	58555251	58555537
ENSE00003535253	58525179	58525359
ENSE00003545087	58538772	58538914
ENSE00003557115	58528475	58528648
ENSE00003594949	58575007	58575129
ENSE00003663698	58523370	58523502
ENSE00003674550	58525989	58526138
ENSE00003678982	58530246	58530347
ENSE00003694120	58538158	58538266
ENSE00003739396	58521183	58521317
ENSE00003784078	58543607	58543903
ENSE00003789675	58531958	58532075
ENSE00003790565	58555784	58555908

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.4567 / max 1093.0895, expressed in 1825 samples.

Highest expression (Bgee): primordial germ cell in gonad, testis, ventricular zone, lower esophagus mucosa, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNOT1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Colon Transverse	eqtl	3.7e-09	-0.11	16:58634662:G:A
Muscle Skeletal	eqtl	1.7e-08	+0.09	16:58511881:C:T
Artery Tibial	sqtl	7.4e-08	-0.39	16:58568852:A:G
Adipose Subcutaneous	eqtl	2.9e-06	-0.12	16:58630161:G:T
Nerve Tibial	sqtl	1.7e-05	-0.37	16:58631485:C:G
Skin Sun Exposed Lower leg	eqtl	2.4e-05	-0.08	16:58634748:G:A
Adipose Visceral Omentum	sqtl	9.2e-05	+0.36	16:58507493:GAAAAC:G
Nerve Tibial	eqtl	1.5e-04	+0.11	16:58648929:C:T
Skin Sun Exposed Lower leg	sqtl	1.8e-04	-0.19	16:58532767:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.7e-04	+0.12	16:58639924:T:A
Adipose Subcutaneous	sqtl	4.2e-04	-0.27	16:58568852:A:G
Whole Blood	sqtl	4.2e-04	+0.38	16:58513618:C:T
Brain Cerebellum	eqtl	9.7e-04	+0.20	16:58644829:G:T
Cells Cultured fibroblasts	sqtl	1.1e-03	+0.86	16:58644774:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.6e-03	+0.29	16:58520237:G:T
Thyroid	sqtl	1.6e-03	+0.18	16:58633117:T:C
Brain Amygdala	eqtl	2.3e-03	+0.20	16:58026707:T:G
Colon Transverse	sqtl	2.7e-03	-0.36	16:58631485:C:G
Cells Cultured fibroblasts	eqtl	2.9e-03	-0.07	16:58633729:C:G
Artery Tibial	eqtl	3.2e-03	-0.06	16:58568321:T:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
157626	59.3168	1825
207909	3.7676	1557
157621	0.5810	330
157624	0.5344	237
157622	0.1465	44
157623	0.1104	31

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.16	gold quality
left testis	UBERON:0004533	99.03	gold quality
right testis	UBERON:0004534	99.01	gold quality
ventricular zone	UBERON:0003053	98.80	gold quality
lower esophagus mucosa	UBERON:0035834	98.49	gold quality
esophagus mucosa	UBERON:0002469	98.38	gold quality
testis	UBERON:0000473	98.35	gold quality
ganglionic eminence	UBERON:0004023	98.24	gold quality
mucosa of transverse colon	UBERON:0004991	98.19	gold quality
esophagus squamous epithelium	UBERON:0006920	98.02	gold quality
epithelium of esophagus	UBERON:0001976	97.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.86	gold quality
skin of abdomen	UBERON:0001416	97.83	gold quality
skin of leg	UBERON:0001511	97.80	gold quality
esophagus	UBERON:0001043	97.71	gold quality
transverse colon	UBERON:0001157	97.62	gold quality
granulocyte	CL:0000094	97.60	gold quality
colonic epithelium	UBERON:0000397	97.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.58	gold quality
right uterine tube	UBERON:0001302	97.52	gold quality
ectocervix	UBERON:0012249	97.52	gold quality
bone marrow cell	CL:0002092	97.50	gold quality
ileal mucosa	UBERON:0000331	97.50	gold quality
embryo	UBERON:0000922	97.45	gold quality
small intestine	UBERON:0002108	97.39	gold quality
minor salivary gland	UBERON:0001830	97.33	gold quality
spleen	UBERON:0002106	97.26	gold quality
body of stomach	UBERON:0001161	97.24	gold quality
vagina	UBERON:0000996	97.22	gold quality
stromal cell of endometrium	CL:0002255	97.19	gold quality
right lung	UBERON:0002167	97.19	gold quality
mouth mucosa	UBERON:0003729	97.18	gold quality
upper lobe of left lung	UBERON:0008952	97.15	gold quality
right adrenal gland cortex	UBERON:0035827	97.15	gold quality
rectum	UBERON:0001052	97.13	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.10	gold quality
intestine	UBERON:0000160	97.08	gold quality
mucosa of stomach	UBERON:0001199	97.08	gold quality
right ovary	UBERON:0002118	97.05	gold quality
tongue squamous epithelium	UBERON:0006919	97.05	gold quality
zone of skin	UBERON:0000014	97.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.03	gold quality
stomach	UBERON:0000945	97.01	gold quality
right adrenal gland	UBERON:0001233	97.01	gold quality
colon	UBERON:0001155	96.99	gold quality
squamous epithelium	UBERON:0006914	96.96	gold quality
lymph node	UBERON:0000029	96.95	gold quality
large intestine	UBERON:0000059	96.95	gold quality
left ovary	UBERON:0002119	96.94	gold quality
lower esophagus	UBERON:0013473	96.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.94	gold quality
endocervix	UBERON:0000458	96.93	gold quality
left uterine tube	UBERON:0001303	96.91	gold quality
male germ cell	CL:0000015	96.89	gold quality
metanephros cortex	UBERON:0010533	96.85	gold quality
left adrenal gland	UBERON:0001234	96.79	gold quality
upper lobe of lung	UBERON:0008948	96.79	gold quality
body of uterus	UBERON:0009853	96.79	gold quality
adenohypophysis	UBERON:0002196	96.77	gold quality
cortical plate	UBERON:0005343	96.77	gold quality
right lobe of thyroid gland	UBERON:0001119	96.76	gold quality
tibial nerve	UBERON:0001323	96.76	gold quality
left adrenal gland cortex	UBERON:0035825	96.76	gold quality
sperm	CL:0000019	96.74	gold quality
left lobe of thyroid gland	UBERON:0001120	96.74	gold quality
tonsil	UBERON:0002372	96.69	gold quality
body of pancreas	UBERON:0001150	96.68	gold quality
sigmoid colon	UBERON:0001159	96.65	gold quality
popliteal artery	UBERON:0002250	96.64	gold quality
tibial artery	UBERON:0007610	96.64	gold quality
adrenal cortex	UBERON:0001235	96.48	gold quality
uterine cervix	UBERON:0000002	96.47	gold quality
right coronary artery	UBERON:0001625	96.44	gold quality
saliva-secreting gland	UBERON:0001044	96.43	gold quality
thyroid gland	UBERON:0002046	96.42	gold quality
pituitary gland	UBERON:0000007	96.36	gold quality
adrenal gland	UBERON:0002369	96.36	gold quality
aorta	UBERON:0000947	96.35	gold quality
pharyngeal mucosa	UBERON:0000355	96.32	gold quality
leukocyte	CL:0000738	96.30	gold quality
vermiform appendix	UBERON:0001154	96.28	gold quality
gastrocnemius	UBERON:0001388	96.24	gold quality
adrenal tissue	UBERON:0018303	96.23	gold quality
monocyte	CL:0000576	96.16	gold quality
fundus of stomach	UBERON:0001160	96.16	gold quality
ovary	UBERON:0000992	96.14	gold quality
mononuclear cell	CL:0000842	96.13	gold quality
islet of Langerhans	UBERON:0000006	96.11	gold quality
pancreas	UBERON:0001264	96.11	gold quality
left coronary artery	UBERON:0001626	96.11	gold quality
caecum	UBERON:0001153	96.09	gold quality
sural nerve	UBERON:0015488	96.09	gold quality
right lobe of liver	UBERON:0001114	96.06	gold quality
descending thoracic aorta	UBERON:0002345	96.05	gold quality
oral cavity	UBERON:0000167	96.04	gold quality
thoracic aorta	UBERON:0001515	96.03	gold quality
peritoneum	UBERON:0002358	96.03	gold quality
omental fat pad	UBERON:0010414	96.03	gold quality
ascending aorta	UBERON:0001496	96.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.16
E-MTAB-6524	no	101.63

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	102.8
Testis	tissue	101.0	high
Thymus	tissue	71.1
Esophagus	tissue	68.7	high
Tonsil	tissue	65.2	high
Colon	tissue	56.3	high
Parathyroid gland	tissue	56.0	high
Lymph node	tissue	54.2	medium
Rectum	tissue	53.8	high
Postcentral gyrus	tissue	53.0
Duodenum	tissue	51.4	high
Small intestine	tissue	49.2	high
Nucleus accumbens	tissue	48.4
Hippocampus	tissue	46.8	medium
Urinary bladder	tissue	45.8	high
Cerebellum	tissue	44.4	high
Appendix	tissue	44.2	high
Locus coeruleus	tissue	43.9
Bone marrow	tissue	43.0	medium
Midbrain	tissue	41.7
Putamen	tissue	41.3
Tongue	tissue	41.2
Thalamus	tissue	41.0
Skin 1	tissue	40.8	high
Superior colliculi	tissue	40.8
Hypothalamus	tissue	40.6
Corpus callosum	tissue	40.6
Medulla oblongata	tissue	40.5
Spinal cord	tissue	40.5
Spleen	tissue	40.2	medium
Substantia nigra	tissue	39.8
Skeletal muscle	tissue	39.7	medium
Thyroid gland	tissue	39.7	high
Stomach 1	tissue	39.6	medium
Periaqueductal gray	tissue	39.5
Pons	tissue	39.0
Septum	tissue	38.9
Pancreas	tissue	38.7	high
Hippocampal formation	tissue	38.5
Ventral forebrain	tissue	37.9
Basal ganglia	tissue	37.8	high
Olfactory bulb	tissue	37.5
Vagina	tissue	37.2	high
Kidney	tissue	37.1	high
Cerebral cortex	tissue	37.0	high
Somatosensory cortex	tissue	37.0
Fallopian tube	tissue	36.6	high
Occipital cortex	tissue	36.3
Motor cortex	tissue	35.6
Prefrontal cortex	tissue	34.8
Temporal cortex	tissue	34.8
Entorhinal cortex	tissue	34.7
Breast	tissue	33.9	high
Retrosplenial and cingulate cortex	tissue	33.9
Amygdala	tissue	33.8
Liver	tissue	33.5	high
Retrosplenial cortex	tissue	33.1
Placenta	tissue	33.0	high
Cervix	tissue	32.6	medium
Insular cortex	tissue	32.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (65.0), Vermis (63.9), Cerebellar cortex (61.3), Corpus callosum, splenium (white matter) (61.2), Corpus callosum, genu (white matter) (60.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CNOT1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 72 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-586	99.65	70.40	2051

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.064, missense Z 9.16 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000317147 splits into 13 regions with different missense tolerance; 3 are missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
16:58,520,961–58,528,581	140 / 324.6	0.43	no
16:58,528,582–58,528,627	0 / 18.1	0.00	yes (p 2.1e-05)
16:58,528,628–58,530,307	25 / 31.2	0.80	no
16:58,530,308–58,532,001	7 / 35.6	0.20	yes (p 1.6e-06)
16:58,532,002–58,537,962	133 / 328.2	0.41	no
16:58,537,963–58,541,620	170 / 273.1	0.62	no
16:58,542,231–58,542,313	3 / 35.1	0.09	yes (p 6.2e-08)
16:58,542,314–58,545,449	133 / 230.4	0.58	no
16:58,545,450–58,546,406	52 / 50.2	1.04	no
16:58,546,407–58,551,626	124 / 289.3	0.43	no
16:58,551,627–58,553,809	77 / 90.5	0.85	no
16:58,553,810–58,555,900	74 / 184.6	0.40	no
16:58,555,901–58,599,337	706 / 1021.2	0.69	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 72.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Panc 08.13 (-1.952), HCC-78 (-1.527), NB-4 (-1.476), KARPAS-299 (-1.443), SLR 20 (-1.443), NCI-H1975 (-1.43), KP-3 (-1.413), EM-2 (-1.385), PE/CA-PJ15 (-1.375), HCC1806 (-1.356), SCC-9 (-1.343), CAS-1 (-1.342), SU-DHL-10 (-1.333), SK-BR-3 (-1.305), G-292, clone A141B1 (-1.298).

Literature-anchored findings (GeneRIF, showing 34)

• purification and characterization of 1.0 MDa yeast CCR4-NOT complex identifies two novel components, CAF40 and CAF130: yeast CAF40 binds human NOT1 (PMID:11733989)
• CNOT1 interacts in a ligand-dependent manner with RXR and represses transcription mediated by several RXR heterodimers. (PMID:16778766)
• Data show that Ccr4-Not function in RNA splicing and nuclear export, and that CNOT1 binds CNOT4 in yeast two-hybrid assays. (PMID:19558367)
• Depletion of CNOT1 induces cell death in a caspase-dependent manner. (PMID:21976065)
• Cnot1, Cnot2, and Cnot3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in mouse and human ESCs. (PMID:22367759)
• The NOT1 MIF4G domain binds CAF1 through a pre-formed interface and leaves the CAF1 catalytic site fully accessible to RNA substrates. (PMID:22977175)
• Authors identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex. (PMID:23644599)
• The CNOT2-CNOT3 heterodimer is stabilized and tightly anchored to the surface of CNOT1 through an unexpected intertwined arrangement of peptide regions lacking defined secondary structure. (PMID:24121232)
• SNP rs7188697 A/G significantly associated with response to dendritic cells therapeutic HIV vaccine (PMID:24433985)
• Crystal structures of the DDX6, CNOT1 and CNOT9 complexes. (PMID:24768538)
• Crystal structure of the DDX6, CNOT9 and CNOT1 complex. (PMID:24768540)
• CNOT1 facilitates recruitment of DDX6 to miRNA-targeted mRNAs, placing DDX6 as a downstream effector in the miRNA silencing pathway. (PMID:25035296)
• Single nucleotide polymorphism in CNOT1 gene is associated with osteosarcoma susceptibility. (PMID:25663449)
• miRNAs, AGOs, GW182, the CCR4-NOT complex, and DDX6/Me31B repress and degrade polyadenylated mRNA targets that are translated via scanning-independent mechanisms in both human and Drosophila melanogaster cells (PMID:27009120)
• we demonstrate that joint deletion of two short conserved motifs that bind UNR and DDX6 relieves repression of 4E-T-bound mRNA, in part reliant on the 4E-T-DDX6-CNOT1 axis. (PMID:27342281)
• YTHDF2 recruits the CCR4-NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m6A-containing RNAs by CAF1 and CCR4. (PMID:27558897)
• the CNOT1-LMNA-Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression, which could be a potential target for gene therapy. (PMID:28188704)
• Increased expression of MHC II genes after knock-down or knock-out of either CNOT1, CNOT2, or CNOT3 subunit was seen in a variety of cell systems and also in naive macrophages from CNOT3 conditional knock-out mice. (PMID:28615693)
• our data suggest the involvement of hNOT-1/ALG3-1 in various molecular contexts determining essential processes associated with distinct cellular machineries and related to various pathologies, such as cancer, viral infections, neuronal and immunological disorders and Congenital Disorders of Glycosylation. (PMID:29547901)
• These results together with the authors’ previous study, have identified that CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTPmediated ICAM1 and IL8 mRNA decay. (PMID:29956766)
• Data suggest that the CCR4-NOT transcription complex subunit 1 (CNOT1)-CCR4-NOT transcription complex subunit 9 (CNOT9) components stimulate deadenylation by the nuclease module. (PMID:30309886)
• CNOT1 Mutation is associated with Holoprosencephaly. (PMID:31006510)
• CNOT1 Mutation is associated with a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development. (PMID:31006513)
• Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. (PMID:31791371)
• A Quantitative Genetic Interaction Map of HIV Infection. (PMID:32084337)
• ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism. (PMID:32311426)
• De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay. (PMID:32553196)
• Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome. (PMID:33397688)
• Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization. (PMID:34615539)
• RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation. (PMID:34887419)
• Structure of the human Ccr4-Not nuclease module using X-ray crystallography and electron paramagnetic resonance spectroscopy distance measurements. (PMID:34923703)
• TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV. (PMID:35013187)
• Vissers-Bodmer syndrome caused by a novel de novo CNOT1 frameshift variant. (PMID:37818768)
• CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection. (PMID:37846490)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnot1	ENSDARG00000004174
mus_musculus	Cnot1	ENSMUSG00000036550
rattus_norvegicus	Cnot1	ENSRNOG00000012271
drosophila_melanogaster	Not1	FBGN0085436
caenorhabditis_elegans		WBGENE00002845

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2442402) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
prolonged QT interval	1
decreased cardiac muscle contractility	1
cardiac muscle necrosis	1
postnatal lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	A0JP85	92.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GOT2	protein-coding	2806
SLC38A7	protein-coding	55238
GINS3	protein-coding	64785
NDRG4	protein-coding	65009
SETD6	protein-coding	79918
LINC02137	ncRNA	105371295
SNORA46	snoRNA	677827
SNORA50A	snoRNA	677830

Protein

Protein identifiers

CCR4-NOT transcription complex subunit 1 — A5YKK6 (reviewed: A5YKK6)

Alternative names: CCR4-associated factor 1, Negative regulator of transcription subunit 1 homolog

All UniProt accessions (10): A5YKK6, H3BMH0, H3BMZ2, H3BNB1, H3BPF1, H3BR89, H3BT18, H3BTH2, H3BU44, H3BVC9

UniProt curated annotations — full annotation on UniProt →

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 embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover.

Subunit / interactions. Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. In the complex, interacts directly with CNOT6, CNOT6L, CNOT7 or CNOT8. Interacts in a ligand-dependent fashion with ESR1 and RXRA. Interacts with NANOS2, TOB1 and ZFP36. Interacts with TNRC6A, TNRC6B or TNRC6C; the interactions are direct. Interacts with YTHDF2; the interaction is direct and promotes recruitment of the CCR4-NOT complex to N6-methyladenosine (m6A)-containing mRNAs, leading to their deadenylation and subsequent degradation. Interacts with EIF4ENIF1/4E-T. Interacts in an RNA-independent manner with BICC1 (via KH domains). Interacts with TEX13A; the interaction may inhibit CNOT1 binding to mRNA and subsequently CNOT1-mediated mRNA degradation. Interacts with HELZ.

Subcellular location. Cytoplasm. P-body. Nucleus.

Tissue specificity. Strongly expressed in brain, heart, thymus, spleen, kidney, liver, placenta and lung. Weakly expressed in skeletal muscle and colon.

Disease relevance. Holoprosencephaly 12 with or without pancreatic agenesis (HPE12) [MIM:618500] A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE12 clinical features include abnormal forebrain development, dysmorphic features, global developmental delay, learning difficulties, and congenital absence of the pancreas in most patients, resulting in early-onset insulin-dependent diabetes mellitus. Other features may include hearing loss and absence of the gallbladder. HPE12 inheritance is autosomal dominant. The disease may be caused by variants affecting the gene represented in this entry. Vissers-Bodmer syndrome (VIBOS) [MIM:619033] An autosomal dominant disorder characterized by global developmental delay, intellectual disability of varying degree, speech delay, motor delay, and hypotonia. Abnormal growth, and cerebral, skeletal, muscle and soft tissue abnormalities are frequently observed. Many patients have behavioral problems, including anxiety, obsessive compulsive disorder, autism spectrum disorder and attention deficit-hyperactivity disorder. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to be important for the association with nuclear receptors.

Similarity. Belongs to the CNOT1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
A5YKK6-1	1	yes
A5YKK6-2	2
A5YKK6-3	3
A5YKK6-4	4

RefSeq proteins (3): NP_001252541, NP_057368, NP_996882 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007196	CCR4-Not_Not1_C	Domain
IPR024557	CNOT1_dom_4	Domain
IPR032191	CNOT1_CAF1_bind	Domain
IPR032193	CNOT1_TTP_bind	Domain
IPR032194	CNOT1_HEAT	Domain
IPR038535	CNOT1_TTP_bind_sf	Homologous_superfamily
IPR040398	Not1	Family
IPR055104	CNOT1_1st	Domain
IPR055454	CNOT1-like_NOT1_connector	Domain

Pfam: PF04054, PF12842, PF16415, PF16417, PF16418, PF22940, PF23590

UniProt features (211 total): helix 120, sequence variant 19, turn 18, strand 16, sequence conflict 9, short sequence motif 7, mutagenesis site 6, splice variant 5, region of interest 4, compositionally biased region 4, modified residue 2, chain 1

Structure

Experimental structures (PDB)

21 structures by resolution:

PDB	Title	Method	Resolution (Å)
4J8S	Crystal structure of human CNOT1 MIF4G domain in complex with a TTP peptide	X-RAY DIFFRACTION	1.55
4CRU	Complex of human CNOT9 and CNOT1 including one tryptophan	X-RAY DIFFRACTION	1.65
4CRW	Complex of human DDX6 (RECA-C) and CNOT1 (MIF4G)	X-RAY DIFFRACTION	1.75
4CT7	CNOT9-CNOT1 complex with bound tryptophan	X-RAY DIFFRACTION	1.9
4CRV	Complex of human CNOT9 and CNOT1 including two tryptophans	X-RAY DIFFRACTION	2.05
4CT6	CNOT9-CNOT1 complex	X-RAY DIFFRACTION	2.1
5ANR	Structure of a human 4E-T - DDX6 - CNOT1 complex	X-RAY DIFFRACTION	2.1
4CT4	CNOT1 MIF4G domain - DDX6 complex	X-RAY DIFFRACTION	2.3
9FL8	Stapled peptide bound to NOT9-NOT1 complex	X-RAY DIFFRACTION	2.64
4GMJ	Structure of human NOT1 MIF4G domain co-crystallized with CAF1	X-RAY DIFFRACTION	2.7
5ONA	Drosophila Bag-of-marbles CBM peptide bound to human CAF40-CNOT1	X-RAY DIFFRACTION	2.7
4CQO	Structure of the human CNOT1 superfamily homology domain in complex with a Nanos1 peptide	X-RAY DIFFRACTION	2.8
9E7T	Cryo-EM structure of NOT1:NOT7:PieF	ELECTRON MICROSCOPY	2.8
8FY3	Structure of NOT1:NOT10:NOT11 module of the human CCR4-NOT complex	ELECTRON MICROSCOPY	2.88
4GML	Crystal structure of human NOT1 MIF4G domain	X-RAY DIFFRACTION	2.9
5FU6	NOT module of the human CCR4-NOT complex (Crystallization mutant)	X-RAY DIFFRACTION	2.9
8BFI	human CNOT1-CNOT10-CNOT11 module	X-RAY DIFFRACTION	3
5FU7	drosophila nanos NBR peptide bound to the NOT module of the human CCR4-NOT complex	X-RAY DIFFRACTION	3.1
4C0D	Structure of the NOT module of the human CCR4-NOT complex (CNOT1-CNOT2-CNOT3)	X-RAY DIFFRACTION	3.2
9E7U	Cryo-EM structure of NOT1:NOT8:PieF	ELECTRON MICROSCOPY	3.5
7VOI	Structure of the human CNOT1(MIF4G)-CNOT6L-CNOT7 complex	X-RAY DIFFRACTION	4.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5YKK6-F1	75.22	0.19

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF uncertain

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2)

Type	Positions
Phosphoserine	318, 1061

Mutagenesis-validated functional residues (6)

Position	Phenotype
1208	impairs interaction with cnot7; when associated with y-1212 and e-1218.
1209	abolishes interaction with cnot7; when associated with y-1257.
1212	impairs interaction with cnot7; when associated with e-1208 and e-1218.
1218	impairs interaction with cnot7; when associated with e-1208 and y-1212.
1251	abolishes interaction with cnot7.
1257	abolishes interaction with cnot7; when associated with y-1209.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-429947	Deadenylation of mRNA	curated
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	curated
R-HSA-429914	Deadenylation-dependent mRNA decay	—
R-HSA-1266738	Developmental Biology	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors	electronic
R-HSA-9816359	Maternal to zygotic transition (MZT)	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 387 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_P_BODY_ASSEMBLY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOMF_NUCLEASE_ACTIVITY, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), trophectodermal cell differentiation (GO:0001829), DNA-templated transcription (GO:0006351), positive regulation of cytoplasmic mRNA processing body assembly (GO:0010606), negative regulation of translation (GO:0017148), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), miRNA-mediated post-transcriptional gene silencing (GO:0035195), negative regulation of retinoic acid receptor signaling pathway (GO:0048387), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), positive regulation of mRNA catabolic process (GO:0061014), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153), regulation of stem cell population maintenance (GO:2000036), regulation of translation (GO:0006417), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (8): RNA binding (GO:0003723), protein domain specific binding (GO:0019904), nuclear estrogen receptor binding (GO:0030331), nuclear retinoic acid receptor binding (GO:0042974), molecular adaptor activity (GO:0060090), armadillo repeat domain binding (GO:0070016), poly(A)-specific ribonuclease activity (GO:0004535), protein binding (GO:0005515)

GO Cellular Component (7): P-body (GO:0000932), nucleus (GO:0005634), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), CCR4-NOT complex (GO:0030014), CCR4-NOT core complex (GO:0030015)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Deadenylation-dependent mRNA decay	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Maternal to zygotic transition (MZT)	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Metabolism of RNA	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1
Developmental Biology	1

GO top-level categories

52 GO namespaces:

Category	Terms
nuclear-transcribed mRNA catabolic process	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	2
translation	2
negative regulation of gene expression	2
positive regulation of mRNA catabolic process	2
nuclear receptor binding	2
binding	2
cellular anatomical structure	2
intracellular protein-containing complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
mRNA destabilization	1
blastocyst formation	1
cell differentiation	1
gene expression	1
RNA biosynthetic process	1
regulation of cytoplasmic mRNA processing body assembly	1
P-body assembly	1
positive regulation of organelle assembly	1
regulation of translation	1
negative regulation of protein metabolic process	1
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
regulatory ncRNA-mediated post-transcriptional gene silencing	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
mRNA catabolic process	1
positive regulation of catabolic process	1
regulation of mRNA catabolic process	1
positive regulation of mRNA metabolic process	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
stem cell population maintenance	1
regulation of developmental process	1
regulation of multicellular organismal process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
protein binding	1
molecular_function	1
protein domain specific binding	1
3’-5’-RNA exonuclease activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
peroxisome	1
microbody membrane	1
cytoplasm	1
CCR4-NOT complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 20 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

20 experimentally-supported GO terms:

GO term	NS	Evidence
miRNA-mediated post-transcriptional gene silencing	BP	direct assay
negative regulation of intracellular estrogen receptor signaling pathway	BP	direct assay
negative regulation of retinoic acid receptor signaling pathway	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
negative regulation of translation	BP	direct assay
positive regulation of cytoplasmic mRNA processing body assembly	BP	direct assay
positive regulation of mRNA catabolic process	BP	mutant phenotype
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	BP	mutant phenotype
positive regulation of nuclear-transcribed mRNA poly(A) tail shortening	BP	direct assay
regulation of stem cell population maintenance	BP	mutant phenotype
CCR4-NOT complex	CC	direct assay
P-body	CC	direct assay
membrane	CC	high-throughput assay
peroxisomal membrane	CC	high-throughput assay
RNA binding	MF	high-throughput assay
armadillo repeat domain binding	MF	physical interaction
molecular adaptor activity	MF	direct assay
nuclear estrogen receptor binding	MF	direct assay
nuclear retinoic acid receptor binding	MF	direct assay
protein domain specific binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,562 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT1	CNOT3	O75175	986
CNOT1	CNOT4	O95628	981
CNOT1	CNOT2	Q9NZN8	978
CNOT1	CNOT7	Q9UIV1	961
CNOT1	CNOT8	Q9UFF9	923
CNOT1	CNOT9	Q92600	848
CNOT1	CNOT6	Q9ULM6	808
CNOT1	CNOT6L	Q96LI5	778
CNOT1	CNOT11	Q9UKZ1	770
CNOT1	CNOT10	Q9H9A5	770
CNOT1	DDX6	P26196	766
CNOT1	XRN1	Q8IZH2	734
CNOT1	DCP2	Q8IU60	710
CNOT1	EDC3	Q96F86	688
CNOT1	EIF4ENIF1	Q9NRA8	676

IntAct

Human interaction partners of CNOT1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 85 partners by confidence:

Partner	Interaction type	MIscore	Records
CNOT7	association	0.880	7
CNOT8	physical association	0.850	6
CNOT6L	association	0.810	5
CNOT11	association	0.770	6
CNOT6	physical association	0.750	3
CNOT2	association	0.740	5
CNOT3	association	0.740	3
TOB1	association	0.710	5
TNRC6C	association	0.690	16
CAPZA2	association	0.640	4
CAPZB	association	0.640	3
TNRC6B	physical association	0.580	4
ANXA2R	association	0.540	3
FANCD2OS	association	0.530	3
RIBC1	association	0.530	3
CNOT10	association	0.530	2
FHL2	association	0.530	2
GPBP1L1	association	0.530	2
MINK1	association	0.530	2
TNKS1BP1	association	0.530	2
CAPZA1	association	0.530	1
PATL1	physical association	0.500	3
TNRC6A	physical association	0.500	2
CFTR	association	0.480	1
DND1	association	0.460	2
AGO2	physical association	0.400	1
CNOT4	physical association	0.370	1
RXRA	physical association	0.370	1
THRB	physical association	0.370	1
PABPN1L	association	0.350	3

BioGRID (525 interactions; top human partners by supporting records): TNRC6A (Reconstituted Complex; 13 records), CNOT2 (Affinity Capture-Western; 12 records), RQCD1 (Co-fractionation; 11 records), CNOT3 (Affinity Capture-Western; 10 records), CNOT7 (Affinity Capture-MS; 10 records), CNOT10 (Affinity Capture-MS; 8 records), CNOT4 (Affinity Capture-Western; 8 records), RC3H1 (Affinity Capture-MS; 8 records), CNOT6L (Affinity Capture-MS; 7 records), CNOT11 (Affinity Capture-MS; 6 records), CNOT6 (Affinity Capture-MS; 6 records), CNOT8 (Affinity Capture-Western; 6 records), RNF219 (Affinity Capture-MS; 6 records), TNKS1BP1 (Affinity Capture-MS; 6 records), CAPZB (Affinity Capture-MS; 5 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CNOT1	“form complex”	“CCR4-NOT complex”	binding

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
CCR4-NOT complex, CNOT7-CNOT6-specific	9	CNOT9, CNOT1, CNOT10, CNOT3, CNOT6, TNKS1BP1, CNOT11, CNOT2, CNOT7
CCR4-NOT complex, CNOT7-CNOT6L-specific	9	CNOT1, CNOT10, CNOT11, CNOT3, CNOT9, TNKS1BP1, CNOT2, CNOT6L, CNOT7
CCR4-NOT complex, CNOT8-CNOT6-specific	9	CNOT9, CNOT1, CNOT11, CNOT2, CNOT3, CNOT6, CNOT8, TNKS1BP1, CNOT10
CCR4-NOT complex, CNOT8-CNOT6L-specific	9	CNOT1, CNOT11, CNOT2, CNOT3, CNOT8, CNOT9, TNKS1BP1, CNOT10, CNOT6L
CCR4-NOT complex	8	CNOT6, CNOT7, CNOT9, CNOT1, CNOT10, CNOT11, CNOT2, CNOT3
CCR4-NOT-TOB1 complex	8	CNOT6L, CNOT7, CNOT9, TOB1, CNOT1, CNOT10, CNOT2, CNOT3
CNOT1-CNOT2-CNOT3 complex	3	CNOT2, CNOT3, CNOT1
4E-T-DDX6-CNOT1 complex	3	CNOT1, DDX6, EIF4ENIF1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	11	96.8×	9e-18
Deadenylation of mRNA	9	67.0×	7e-13
M-decay: degradation of maternal mRNAs by maternally stored factors	11	60.8×	2e-15
TGFBR3 expression	5	38.7×	7e-06
Regulation of MECP2 expression and activity	5	31.2×	2e-05
Transcriptional Regulation by MECP2	5	26.9×	4e-05
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	5	26.2×	4e-05
MTOR signalling	5	22.5×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	10	102.9×	6e-16
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	6	86.4×	7e-09
regulatory ncRNA-mediated gene silencing	8	69.1×	4e-11
regulation of translation	8	22.4×	3e-07
negative regulation of translation	5	12.6×	3e-03

Disease & clinical

Genetic variants

Variant evidence for CNOT1: 1,019 ClinVar records (53 pathogenic / likely pathogenic); 111 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,019 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	34
Uncertain significance	494
Likely benign	292
Benign	97

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 53 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
619606	NM_016284.5(CNOT1):c.1603C>T (p.Arg535Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1804087	NM_016284.5(CNOT1):c.434-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4075809	NM_016284.5(CNOT1):c.4800+1G>A	Pathogenic	criteria provided, single submitter	2
1328840	NM_016284.5(CNOT1):c.638-1G>A	Pathogenic	criteria provided, single submitter	1
1700187	NM_016284.5(CNOT1):c.3562G>T (p.Asp1188Tyr)	Pathogenic	criteria provided, single submitter	1
1700194	NM_016284.5(CNOT1):c.4321G>A (p.Ala1441Thr)	Pathogenic	criteria provided, single submitter	1
2430374	NM_016284.5(CNOT1):c.1343+1G>T	Pathogenic	criteria provided, single submitter	1
2442368	NM_016284.5(CNOT1):c.3055C>T (p.Gln1019Ter)	Pathogenic	criteria provided, single submitter	1
3382694	NM_016284.5(CNOT1):c.371_372dup (p.Gln125fs)	Pathogenic	criteria provided, single submitter	1
3494452	NM_016284.5(CNOT1):c.2834del (p.Pro945fs)	Pathogenic	criteria provided, single submitter	1
3767105	NM_016284.5(CNOT1):c.304C>T (p.Gln102Ter)	Pathogenic	criteria provided, single submitter	1
3777073	NM_016284.5(CNOT1):c.445dup (p.Ile149fs)	Pathogenic	criteria provided, single submitter	1
4230903	NM_016284.5(CNOT1):c.5749dup (p.Gln1917fs)	Pathogenic	criteria provided, single submitter	1
4230904	NM_016284.5(CNOT1):c.394dup (p.Ala132fs)	Pathogenic	criteria provided, single submitter	1
4688828	NM_016284.5(CNOT1):c.144dup (p.Arg49fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CNOT1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 4,036):

Position(s)	Effect	Δscore	Sites
16:58521318–58521319	acceptor_loss	1.0000	4
16:58523369	donor_loss	1.0000	2
16:58523503–58523504	acceptor_loss	1.0000	5
16:58525177–58525178	donor_loss	1.0000	5
16:58525361	acceptor_loss	1.0000
16:58525987	donor_gain	1.0000
16:58525987–58525988	donor_loss	1.0000	4
16:58526139–58526140	acceptor_loss	1.0000	6
16:58526143	acceptor_gain	1.0000
16:58526148	acceptor_gain	1.0000

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 15,703 scored), across 1,255 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1996	9	0.977	0.998
M1452	9	0.976	1.000
M2140	9	0.967	0.997
M1136	9	0.947	0.999
M2248	9	0.941	0.997
M1883	9	0.938	1.000
M1553	9	0.906	0.999
M1444	9	0.899	0.998
M1905	9	0.887	0.991
M1832	9	0.880	0.996
N1105	8	0.999	1.000
D1188	8	0.999	1.000
F1281	8	0.999	1.000
D1427	8	0.999	1.000
D1892	8	0.999	1.000
D1937	8	0.999	1.000
H2104	8	0.999	1.000
D2105	8	0.999	1.000
D2249	8	0.999	1.000
F1101	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.19e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000275

Disease associations

OMIM: gene MIM:604917 | disease phenotypes: MIM:619033, MIM:618500, MIM:236100, MIM:618840

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
holoprosencephaly 12 with or without pancreatic agenesis	Strong	Autosomal dominant	4
Vissers-Bodmer syndrome	Strong	Autosomal dominant	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD
holoprosencephaly 12 with or without pancreatic agenesis	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
Cerebral malformation	green
DDG2P	green
Fetal anomalies	green
Holoprosencephaly	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Neonatal diabetes	green
Paediatric disorders	green

Mondo (6): intellectual disability (MONDO:0001071), Vissers-Bodmer syndrome (MONDO:0033618), holoprosencephaly 12 with or without pancreatic agenesis (MONDO:0032787), complex neurodevelopmental disorder (MONDO:0100038), holoprosencephaly (MONDO:0016296), alopecia-intellectual disability syndrome 4 (MONDO:0030009)

Orphanet (3): Non-specific syndromic intellectual disability (Orphanet:528084), Holoprosencephaly (Orphanet:2162), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

23 phenotypes (HPO-id order):

HPO	Term
HP:0000218	High palate
HP:0000269	Prominent occiput
HP:0000340	Sloping forehead
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000601	Hypotelorism
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0001274	Agenesis of corpus callosum
HP:0001360	Holoprosencephaly
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0002507	Semilobar holoprosencephaly
HP:0006315	Solitary median maxillary central incisor
HP:0009658	Aplasia/Hypoplasia of the phalanges of the thumb
HP:0010669	Hypoplasia of the zygomatic bone
HP:0010938	Abnormal external nose morphology
HP:0011467	Absent gallbladder
HP:0012418	Hypoxemia
HP:0012443	Abnormal brain morphology
HP:0030795	Decreased circulating C-peptide concentration
HP:0031209	Decreased circulating lipoprotein lipase concentration
HP:0100801	Pancreatic aplasia
HP:0410289	Hypoamylasemia

GWAS associations

showing 30 of 111 associations:

Study	Trait	p-value
GCST010919_26	QT interval	4e-63
GCST002500_3	QT interval	2e-57
GCST010796_4621	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-52
GCST010796_4859	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-52
GCST010796_4860	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-52
GCST010796_4867	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-51
GCST010796_4863	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-50
GCST010796_4855	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-50
GCST010796_4866	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-50
GCST010796_4862	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-49
GCST010796_4854	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-49
GCST010796_4856	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-49
GCST010796_4868	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-49
GCST010796_4864	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-49
GCST010796_4858	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-49
GCST010796_4861	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-48
GCST010796_4865	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-48
GCST010796_4857	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-48
GCST010796_4852	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-47
GCST010796_4853	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-47
GCST010796_4869	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-47
GCST010796_4871	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-46
GCST010796_4870	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-46
GCST010796_4851	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-46
GCST010796_4872	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-46
GCST010796_4568	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-44
GCST010796_4566	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-44
GCST010796_4567	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-44
GCST010796_4873	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-43
GCST010796_4562	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-42

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0005763	pulse pressure measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0004309	platelet count
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105919 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.69	Kd	20.31	nM	CHEMBL5653589
7.69	ED50	20.31	nM	CHEMBL5653589
7.16	Kd	68.75	nM	CHEMBL3752910
7.16	ED50	68.75	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 9 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148098: Binding affinity to human CNOT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0203	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148098: Binding affinity to human CNOT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0688	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, affects folding, affects reaction, affects cotreatment, increases methylation (+2 more)	4
bisphenol S	affects folding, decreases reaction, affects binding	2
bisphenol AF	affects binding, affects folding, affects reaction, decreases reaction	2
Estradiol	affects binding, decreases reaction, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases methylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Ribonucleotides	affects binding	1
Tamoxifen	decreases reaction, affects binding	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Metribolone	affects binding, affects folding, affects reaction	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012557	Binding	Binding affinity to CCR4-NOT transcription complex subunit 1 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UN	Abcam HEK293T CNOT1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CNOT1 across ~30M SureChEMBL compounds — explore on Sugi Predict.