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 and cytosol. Part of CCR4-NOT complex. Implicated in Vissers-Bodmer syndrome and holoprosencephaly 12.

Source: NCBI Gene 23019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 111
• Clinical variants (ClinVar): 948 total — 19 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 72.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_016284

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: 27 — 16 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

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

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.

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

295 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting CNOT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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.

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

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 (199 total): helix 108, turn 19, sequence variant 19, strand 15, 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.

PDB	Method	Resolution (Å)
4J8S	X-RAY DIFFRACTION	1.55
4CRU	X-RAY DIFFRACTION	1.65
4CRW	X-RAY DIFFRACTION	1.75
4CT7	X-RAY DIFFRACTION	1.9
4CRV	X-RAY DIFFRACTION	2.05
4CT6	X-RAY DIFFRACTION	2.1
5ANR	X-RAY DIFFRACTION	2.1
4CT4	X-RAY DIFFRACTION	2.3
9FL8	X-RAY DIFFRACTION	2.64
4GMJ	X-RAY DIFFRACTION	2.7
5ONA	X-RAY DIFFRACTION	2.7
4CQO	X-RAY DIFFRACTION	2.8
9E7T	ELECTRON MICROSCOPY	2.8
8FY3	ELECTRON MICROSCOPY	2.88
4GML	X-RAY DIFFRACTION	2.9
5FU6	X-RAY DIFFRACTION	2.9
8BFI	X-RAY DIFFRACTION	3
5FU7	X-RAY DIFFRACTION	3.1
4C0D	X-RAY DIFFRACTION	3.2
9E7U	ELECTRON MICROSCOPY	3.5
7VOI	X-RAY DIFFRACTION	4.38

Predicted structure (AlphaFold)

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

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): 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

3 pathways

ID	Pathway
R-HSA-429947	Deadenylation of mRNA
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors

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 (15): 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), 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 (9): P-body (GO:0000932), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), CCR4-NOT complex (GO:0030014), CCR4-NOT core complex (GO:0030015), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deadenylation-dependent mRNA decay	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
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
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
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 interactions and networks

STRING

3034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT1	CNOT2	Q9NZN8	999
CNOT1	CNOT3	O75175	999
CNOT1	CNOT4	O95628	999
CNOT1	CNOT8	Q9UFF9	999
CNOT1	CNOT7	Q9UIV1	998
CNOT1	CNOT9	Q92600	997
CNOT1	CNOT11	Q9UKZ1	995
CNOT1	CNOT10	Q9H9A5	995
CNOT1	CNOT6	Q9ULM6	995
CNOT1	DDX6	P26196	991
CNOT1	CNOT6L	Q96LI5	988
CNOT1	TNRC6A	Q8NDV7	986
CNOT1	YTHDF2	Q9Y5A9	980
CNOT1	ZFP36	P26651	879
CNOT1	NANOS2	P60321	863

IntAct

241 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CNOT7	CNOT1	psi-mi:“MI:0914”(association)	0.880
CNOT8	CNOT1	psi-mi:“MI:0915”(physical association)	0.850
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
CNOT6L	CNOT1	psi-mi:“MI:0915”(physical association)	0.810
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
CNOT11	CNOT1	psi-mi:“MI:0915”(physical association)	0.770
CNOT6	CNOT1	psi-mi:“MI:0915”(physical association)	0.750
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT2	CNOT1	psi-mi:“MI:0915”(physical association)	0.740
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
TOB1	CNOT1	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TNRC6C	CNOT1	psi-mi:“MI:0914”(association)	0.690

BioGRID (485): CNOT1 (Affinity Capture-MS), CNOT1 (Reconstituted Complex), CNOT1 (Affinity Capture-Western), CNOT1 (Affinity Capture-MS), CNOT1 (Affinity Capture-MS), CNOT1 (Affinity Capture-Western), CNOT1 (Affinity Capture-Western), CNOT2 (Affinity Capture-Western), CNOT3 (Affinity Capture-Western), CNOT8 (Affinity Capture-Western), CNOT1 (Affinity Capture-Western), CNOT1 (Affinity Capture-Western), RXRA (Two-hybrid), Esr1 (Two-hybrid), CNOT1 (Affinity Capture-MS)

ESM2 similar proteins: A0JP85, A1A5H6, A2AGH6, A5GFY4, A5YKK6, B1AY13, B4KJ11, E9Q8I9, O75448, O94915, O95155, P55824, Q0KK59, Q23658, Q24134, Q2PW47, Q2QCI8, Q4V8B3, Q5F3M0, Q5RCU2, Q5RFA0, Q5TBA9, Q60PC0, Q6GLR7, Q6GYQ0, Q6PI53, Q6ZQ08, Q7ZYV9, Q80TJ1, Q80X82, Q80YV3, Q8BHR2, Q8BL99, Q8IXH7, Q8R0Z2, Q8R1A4, Q922L6, Q92797, Q93074, Q96N67

Diamond homologs: A0JP85, A1A5H6, A5YKK6, Q20937, Q6ZQ08

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 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	63.4×	1e-15
Deadenylation of mRNA	9	43.9×	4e-11
M-decay: degradation of maternal mRNAs by maternally stored factors	10	36.2×	2e-11
Transcriptional Regulation by MECP2	5	17.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	10	65.8×	9e-14
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	5	46.0×	1e-05
regulatory ncRNA-mediated gene silencing	7	38.7×	2e-07
regulation of translation	8	14.3×	2e-05
negative regulation of translation	8	12.8×	3e-05
protein phosphorylation	9	5.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	28
Uncertain significance	454
Likely benign	270
Benign	104

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1328840	NM_016284.5(CNOT1):c.638-1G>A	Pathogenic
1700187	NM_016284.5(CNOT1):c.3562G>T (p.Asp1188Tyr)	Pathogenic
1700194	NM_016284.5(CNOT1):c.4321G>A (p.Ala1441Thr)	Pathogenic
1804087	NM_016284.5(CNOT1):c.434-2A>G	Pathogenic
2430374	NM_016284.5(CNOT1):c.1343+1G>T	Pathogenic
2442368	NM_016284.5(CNOT1):c.3055C>T (p.Gln1019Ter)	Pathogenic
2580293	GRCh37/hg19 16q21(chr16:58587636-58610536)x1	Pathogenic
3382694	NM_016284.5(CNOT1):c.371_372dup (p.Gln125fs)	Pathogenic
3494452	NM_016284.5(CNOT1):c.2834del (p.Pro945fs)	Pathogenic
3767105	NM_016284.5(CNOT1):c.304C>T (p.Gln102Ter)	Pathogenic
3777073	NM_016284.5(CNOT1):c.445dup (p.Ile149fs)	Pathogenic
4075809	NM_016284.5(CNOT1):c.4800+1G>A	Pathogenic
4230903	NM_016284.5(CNOT1):c.5749dup (p.Gln1917fs)	Pathogenic
4230904	NM_016284.5(CNOT1):c.394dup (p.Ala132fs)	Pathogenic
4688828	NM_016284.5(CNOT1):c.144dup (p.Arg49fs)	Pathogenic
4820090	NM_016284.5(CNOT1):c.763_764del (p.Leu255fs)	Pathogenic
619606	NM_016284.5(CNOT1):c.1603C>T (p.Arg535Cys)	Pathogenic
978821	NM_016284.5(CNOT1):c.97C>T (p.Gln33Ter)	Pathogenic
978823	NM_016284.5(CNOT1):c.2698C>T (p.Arg900Cys)	Pathogenic
1172633	NM_016284.5(CNOT1):c.2318C>G (p.Ser773Ter)	Likely pathogenic
1195433	NM_016284.5(CNOT1):c.6047_6050del (p.Leu2016fs)	Likely pathogenic
1343159	NM_016284.5(CNOT1):c.1004_1005dup (p.Trp336fs)	Likely pathogenic
1343213	NM_016284.5(CNOT1):c.6196delinsAA (p.Gln2066fs)	Likely pathogenic
1700080	NM_016284.5(CNOT1):c.6178-2A>G	Likely pathogenic
1709232	NM_016284.5(CNOT1):c.3750+5G>A	Likely pathogenic
1710395	NM_016284.5(CNOT1):c.3811C>T (p.Gln1271Ter)	Likely pathogenic
1804086	NM_016284.5(CNOT1):c.550del (p.Leu184fs)	Likely pathogenic
2505815	NM_016284.5(CNOT1):c.6970A>C (p.Ile2324Leu)	Likely pathogenic
2636715	NM_016284.5(CNOT1):c.2751dup (p.Gly918fs)	Likely pathogenic
2672638	NM_016284.5(CNOT1):c.4434+1del	Likely pathogenic

SpliceAI

7566 predictions. Top by Δscore:

Variant	Effect	Δscore
16:58521181:A:AC	donor_gain	1.0000
16:58521182:C:CT	donor_gain	1.0000
16:58521182:CTTTT:C	donor_gain	1.0000
16:58521313:GAACT:G	acceptor_gain	1.0000
16:58521314:AACT:A	acceptor_gain	1.0000
16:58521316:CT:C	acceptor_gain	1.0000
16:58521318:C:CC	acceptor_gain	1.0000
16:58521318:CTGG:C	acceptor_loss	1.0000
16:58521319:T:A	acceptor_loss	1.0000
16:58523365:CTTA:C	donor_loss	1.0000
16:58523366:TTA:T	donor_loss	1.0000
16:58523367:TA:T	donor_loss	1.0000
16:58523368:A:AC	donor_gain	1.0000
16:58523368:A:AT	donor_loss	1.0000
16:58523368:AC:A	donor_gain	1.0000
16:58523369:C:CC	donor_gain	1.0000
16:58523369:C:CT	donor_loss	1.0000
16:58523369:CC:C	donor_gain	1.0000
16:58523369:CCTT:C	donor_gain	1.0000
16:58523499:CGAC:C	acceptor_gain	1.0000
16:58523502:CCT:C	acceptor_loss	1.0000
16:58523503:C:CC	acceptor_gain	1.0000
16:58523503:CTAGA:C	acceptor_loss	1.0000
16:58523504:T:C	acceptor_loss	1.0000
16:58525174:CTCA:C	donor_loss	1.0000
16:58525175:TCACC:T	donor_loss	1.0000
16:58525176:CACCC:C	donor_loss	1.0000
16:58525177:A:AC	donor_gain	1.0000
16:58525177:AC:A	donor_gain	1.0000
16:58525177:ACC:A	donor_gain	1.0000

AlphaMissense

15703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:58521020:C:G	A2357P	1.000
16:58521022:A:T	V2356D	1.000
16:58521031:A:G	F2353S	1.000
16:58521034:A:G	L2352S	1.000
16:58521209:A:C	F2342L	1.000
16:58521209:A:T	F2342L	1.000
16:58521210:A:C	F2342C	1.000
16:58521210:A:G	F2342S	1.000
16:58521211:A:G	F2342L	1.000
16:58521221:C:A	W2338C	1.000
16:58521221:C:G	W2338C	1.000
16:58521223:A:G	W2338R	1.000
16:58521223:A:T	W2338R	1.000
16:58521224:G:C	F2337L	1.000
16:58521224:G:T	F2337L	1.000
16:58521225:A:C	F2337C	1.000
16:58521225:A:G	F2337S	1.000
16:58521226:A:G	F2337L	1.000
16:58521249:A:G	L2329P	1.000
16:58521267:A:G	L2323P	1.000
16:58521267:A:T	L2323H	1.000
16:58521270:A:G	L2322P	1.000
16:58521270:A:T	L2322H	1.000
16:58521273:C:A	G2321V	1.000
16:58521273:C:T	G2321D	1.000
16:58521274:C:A	G2321C	1.000
16:58521274:C:G	G2321R	1.000
16:58521275:C:A	W2320C	1.000
16:58521275:C:G	W2320C	1.000
16:58521277:A:G	W2320R	1.000

dbSNP variants (sampled 300 via entrez): RS1000021538 (16:58604859 G>A), RS1000053846 (16:58552581 C>A), RS1000073867 (16:58521497 G>C), RS1000091086 (16:58573848 A>C,G), RS1000106001 (16:58594341 A>T), RS1000119900 (16:58610624 A>G), RS1000140043 (16:58570674 T>C), RS1000142311 (16:58593503 G>A), RS1000167140 (16:58540839 G>C), RS1000215097 (16:58629206 G>C), RS1000256826 (16:58590179 G>C), RS1000274532 (16:58573644 C>A,G), RS1000276945 (16:58593222 G>C), RS1000288476 (16:58576933 A>G), RS1000362093 (16:58625513 A>T)

Disease associations

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

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (2)

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

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

Mondo (7): holoprosencephaly 12 with or without pancreatic agenesis (MONDO:0032787), intellectual disability (MONDO:0001071), Vissers-Bodmer syndrome (MONDO:0033618), neurodevelopmental disorder (MONDO:0700092), 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 total (23 of 23 shown, 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	Reduced C-peptide level
HP:0031209	Decreased circulating lipoprotein lipase concentration
HP:0100801	Pancreatic aplasia
HP:0410289	Hypoamylasemia

GWAS associations

111 associations (top):

Study	Trait	p-value
GCST000363_9	QT interval	3.000000e-25
GCST001580_3	QT interval	1.000000e-07
GCST002500_18	QT interval	2.000000e-57
GCST002500_30	QT interval	6.000000e-09
GCST002539_83	Schizophrenia	2.000000e-08
GCST004521_102	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_239	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST006629_5	Pulse pressure	1.000000e-13
GCST006803_60	Schizophrenia	2.000000e-10
GCST007201_203	Schizophrenia	2.000000e-07
GCST007201_333	Schizophrenia	6.000000e-08
GCST007218_12	QT interval	1.000000e-20
GCST010135_44	Oily fish consumption	2.000000e-08
GCST010140_34	Pork consumption	2.000000e-08
GCST010241_416	Apolipoprotein A1 levels	3.000000e-10
GCST010242_203	HDL cholesterol levels	6.000000e-09
GCST010320_139	PR interval	2.000000e-12
GCST010321_52	PR interval	9.000000e-15
GCST010796_3426	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-42
GCST010796_3427	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-44
GCST010796_3428	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-44
GCST010796_3429	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-44
GCST010796_3451	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-22
GCST010796_3452	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-21
GCST010796_3453	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-21
GCST010796_3454	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-23
GCST010796_3455	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_3456	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_3457	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-24
GCST010796_3458	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23

EFO canonical traits (9, from GWAS)

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 (3)

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
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105919 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11866002	CNOT1		0.00	0

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 folding, affects reaction, affects cotreatment, increases methylation, decreases reaction (+2 more)	4
bisphenol S	affects folding, decreases reaction, affects binding	2
bisphenol AF	affects folding, affects reaction, decreases reaction, affects binding	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	affects binding, decreases reaction	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)

298 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	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	PHASE3	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	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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