CNOT11

Summary

CNOT11 (CCR4-NOT transcription complex subunit 11, HGNC:25217) is a protein-coding gene on chromosome 2q11.2, encoding CCR4-NOT transcription complex subunit 11 (Q9UKZ1). 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 regul…. It is a selective cancer dependency (DepMap: 10.4% of cell lines).

Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Part of CCR4-NOT complex.

Source: NCBI Gene 55571 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.4% of screened cell lines
• MANE Select transcript: NM_017546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25217
Approved symbol	CNOT11
Name	CCR4-NOT transcription complex subunit 11
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	C40
Ensembl gene	ENSG00000158435
Ensembl biotype	protein_coding
OMIM	620509
Entrez	55571

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000289382, ENST00000420107, ENST00000462489, ENST00000875193, ENST00000875194, ENST00000875195, ENST00000875196, ENST00000875197, ENST00000957664, ENST00000957665

RefSeq mRNA: 1 — MANE Select: NM_017546 NM_017546

CCDS: CCDS2050

Canonical transcript exons

ENST00000289382 — 7 exons

Exon	Start	End
ENSE00001038906	101266677	101266879
ENSE00001038911	101269040	101269136
ENSE00001038913	101262539	101262691
ENSE00001038915	101257791	101257955
ENSE00001164160	101252886	101253478
ENSE00001249069	101269216	101270316
ENSE00003556579	101264845	101265047

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8540 / max 303.3167, expressed in 1814 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21613	24.1492	1814
21611	1.0222	588
21609	0.7781	481
21612	0.4776	251
21610	0.2575	123
21618	0.1106	11
21619	0.0294	1
21615	0.0167	7
21617	0.0069	2
21616	0.0058	2

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.34	gold quality
secondary oocyte	CL:0000655	97.69	gold quality
ileal mucosa	UBERON:0000331	97.61	gold quality
oviduct epithelium	UBERON:0004804	97.42	gold quality
left ventricle myocardium	UBERON:0006566	95.29	gold quality
tibialis anterior	UBERON:0001385	94.63	gold quality
rectum	UBERON:0001052	94.61	gold quality
body of pancreas	UBERON:0001150	93.95	gold quality
mucosa of transverse colon	UBERON:0004991	93.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.57	gold quality
granulocyte	CL:0000094	93.38	gold quality
bone marrow cell	CL:0002092	93.07	gold quality
right uterine tube	UBERON:0001302	92.97	gold quality
esophagus mucosa	UBERON:0002469	92.86	gold quality
lower esophagus mucosa	UBERON:0035834	92.57	gold quality
body of stomach	UBERON:0001161	92.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.49	gold quality
pancreas	UBERON:0001264	92.48	gold quality
islet of Langerhans	UBERON:0000006	92.45	gold quality
transverse colon	UBERON:0001157	92.30	gold quality
adrenal tissue	UBERON:0018303	92.24	gold quality
fallopian tube	UBERON:0003889	92.11	gold quality
vermiform appendix	UBERON:0001154	91.87	gold quality
gall bladder	UBERON:0002110	91.71	gold quality
stomach	UBERON:0000945	91.69	gold quality
small intestine	UBERON:0002108	91.62	gold quality
endometrium	UBERON:0001295	91.61	gold quality
gastrocnemius	UBERON:0001388	91.61	gold quality
right atrium auricular region	UBERON:0006631	91.60	gold quality
heart left ventricle	UBERON:0002084	91.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting CNOT11, 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-1193	100.00	65.93	529
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-3160-5P	99.28	69.07	1938

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• CNOT11 interacts with the first amino acids of CNOT1 and with CNOT10 and is required for the association of CNOT10 with the CCR4-NOT complex. (PMID:23232451)
• Human CNOT10 and CNOT11 form a complex that interacts with the CNOT1 N-terminal domain. (PMID:23303381)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnot11	ENSDARG00000068596
mus_musculus	Cnot11	ENSMUSG00000003135
rattus_norvegicus	Cnot11	ENSRNOG00000023220
drosophila_melanogaster	Not11	FBGN0034963
caenorhabditis_elegans		WBGENE00013530

Protein

Protein identifiers

CCR4-NOT transcription complex subunit 11 — Q9UKZ1 (reviewed: Q9UKZ1)

All UniProt accessions (2): Q9UKZ1, H7C0C7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is required for the association of CNOT10 with the CCR4-NOT complex. Does not seem to be required for complex deadenylase function.

Subunit / interactions. Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. CNOT10 and CNOT11 form a subcomplex docked to the CNOT1 scaffold.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the CNOT11 family.

RefSeq proteins (1): NP_060016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019312	CNOT11_C	Domain

Pfam: PF10155

UniProt features (42 total): helix 28, turn 5, region of interest 2, strand 2, compositionally biased region 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8BFH	X-RAY DIFFRACTION	2.2
8BFJ	X-RAY DIFFRACTION	2.23
8FY3	ELECTRON MICROSCOPY	2.88
8BFI	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKZ1-F1	78.45	0.42

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 (1): 41

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: 97 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, REACTOME_DEADENYLATION_OF_MRNA, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY, GOBP_NUCLEAR_TRANSCRIBED_MRNA_POLY_A_TAIL_SHORTENING, ACTTTAT_MIR1425P, WHN_B, NERF_Q2, REACTOME_METABOLISM_OF_RNA, GOBP_REGULATION_OF_TRANSLATION

GO Biological Process (3): nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), regulation of translation (GO:0006417), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), CCR4-NOT complex (GO:0030014), 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	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
negative regulation of gene expression	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT11	CNOT1	A5YKK6	995
CNOT11	CNOT10	Q9H9A5	994
CNOT11	CNOT2	Q9NZN8	992
CNOT11	CNOT3	O75175	991
CNOT11	CNOT9	Q92600	988
CNOT11	CNOT6	Q9ULM6	918
CNOT11	CNOT6L	Q96LI5	872
CNOT11	CNOT4	O95628	867
CNOT11	CNOT7	Q9UIV1	854
CNOT11	CNOT8	Q9UFF9	802
CNOT11	CNOT12	Q9C0C2	682
CNOT11	POLR3H	Q9Y535	521
CNOT11	CDK5RAP1	Q96SZ6	507
CNOT11	DDX6	P26196	502
CNOT11	POLR3F	Q9H1D9	479

IntAct

128 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
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
CNOT11	CNOT1	psi-mi:“MI:0915”(physical association)	0.770
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
GPBP1L1	CNOT11	psi-mi:“MI:0915”(physical association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT10	CNOT11	psi-mi:“MI:0915”(physical association)	0.740
CNOT11	CNOT10	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
MEOX1	CNOT11	psi-mi:“MI:0915”(physical association)	0.560
FAM193B	CNOT11	psi-mi:“MI:0915”(physical association)	0.560
C2CD6	CNOT11	psi-mi:“MI:0915”(physical association)	0.560
CNOT11	Cnot7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (180): CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Proximity Label-MS), CNOT11 (Proximity Label-MS), CNOT11 (Proximity Label-MS), CNOT11 (Proximity Label-MS), CNOT11 (Proximity Label-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS)

ESM2 similar proteins: A0JMF8, A2RSY1, A6QLW9, B1WAV2, B2GV50, O60271, O75069, O77627, P05412, P05627, P0C090, P17325, P22670, P48377, P48378, P48379, P48380, P48381, P56432, Q0V989, Q0V9K5, Q16656, Q32NR3, Q3KR73, Q499B3, Q49GP3, Q4R3I8, Q4R3Z4, Q4V872, Q4VGL6, Q58A65, Q5EAP5, Q5EY87, Q5RDR2, Q5RJA1, Q5TC82, Q62739, Q66IV1, Q6NRE7, Q6NUC6

Diamond homologs: A4QP78, B0BNA9, Q1ZXI2, Q9CWN7, Q9UKZ1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CNOT11	“form complex”	“CCR4-NOT complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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	9	99.4×	3e-14
Deadenylation of mRNA	8	74.8×	9e-12
M-decay: degradation of maternal mRNAs by maternally stored factors	9	62.5×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	8	85.6×	1e-11
regulatory ncRNA-mediated gene silencing	6	53.9×	3e-07
negative regulation of translation	6	15.7×	3e-04
regulation of translation	5	14.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

957 predictions. Top by Δscore:

Variant	Effect	Δscore
2:101257951:GGCCG:G	donor_gain	1.0000
2:101257952:GCCG:G	donor_gain	1.0000
2:101257952:GCCGG:G	donor_gain	1.0000
2:101257955:GGTAA:G	donor_loss	1.0000
2:101257956:G:A	donor_loss	1.0000
2:101257956:G:GG	donor_gain	1.0000
2:101257957:T:A	donor_loss	1.0000
2:101262533:TTCCA:T	acceptor_loss	1.0000
2:101262534:TCCA:T	acceptor_loss	1.0000
2:101262536:CAG:C	acceptor_loss	1.0000
2:101262537:A:AG	acceptor_gain	1.0000
2:101262537:A:AT	acceptor_loss	1.0000
2:101262538:G:GG	acceptor_gain	1.0000
2:101262538:GA:G	acceptor_gain	1.0000
2:101262538:GAAC:G	acceptor_gain	1.0000
2:101262688:GAAA:G	donor_gain	1.0000
2:101262690:AAG:A	donor_loss	1.0000
2:101262691:AG:A	donor_loss	1.0000
2:101262692:G:A	donor_loss	1.0000
2:101262692:GTAG:G	donor_gain	1.0000
2:101266659:A:G	acceptor_gain	1.0000
2:101269214:A:AG	acceptor_gain	1.0000
2:101269215:G:GG	acceptor_gain	1.0000
2:101269215:GA:G	acceptor_gain	1.0000
2:101253564:G:T	donor_gain	0.9900
2:101257836:A:AG	acceptor_gain	0.9900
2:101257837:G:GG	acceptor_gain	0.9900
2:101257961:G:GT	donor_gain	0.9900
2:101262531:A:AG	acceptor_gain	0.9900
2:101262532:T:G	acceptor_gain	0.9900

AlphaMissense

3330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:101253277:G:C	G105R	1.000
2:101253278:G:A	G105D	1.000
2:101253314:T:C	L117P	1.000
2:101253353:T:C	L130P	1.000
2:101253356:T:C	L131P	1.000
2:101253358:T:A	W132R	1.000
2:101253358:T:C	W132R	1.000
2:101253361:G:A	E133K	1.000
2:101253397:T:C	F145L	1.000
2:101253399:C:A	F145L	1.000
2:101253399:C:G	F145L	1.000
2:101253401:C:A	A146D	1.000
2:101257827:T:C	F184S	1.000
2:101257830:T:A	L185H	1.000
2:101257830:T:C	L185P	1.000
2:101257839:T:C	L188P	1.000
2:101264910:T:A	W300R	1.000
2:101264910:T:C	W300R	1.000
2:101264946:T:A	W312R	1.000
2:101264946:T:C	W312R	1.000
2:101265009:G:C	A333P	1.000
2:101265010:C:A	A333D	1.000
2:101266678:T:C	L346P	1.000
2:101266711:T:A	V357D	1.000
2:101266741:T:A	L367H	1.000
2:101266741:T:C	L367P	1.000
2:101266750:T:A	L370H	1.000
2:101266750:T:C	L370P	1.000
2:101266750:T:G	L370R	1.000
2:101266752:G:A	V371M	1.000

dbSNP variants (sampled 300 via entrez): RS1000055269 (2:101255393 G>C), RS1000087254 (2:101265211 G>A), RS1000157486 (2:101260717 T>A), RS1000444971 (2:101252775 A>C,T), RS1000649038 (2:101258343 A>C), RS1000674289 (2:101254351 G>A), RS1000906164 (2:101270717 A>G), RS1001058494 (2:101263938 A>C,G), RS1001089441 (2:101263560 G>A,C), RS1001130479 (2:101254094 A>C), RS1001338354 (2:101270467 A>G), RS1001355508 (2:101252807 C>G,T), RS1001390217 (2:101259157 A>C,G), RS1001421279 (2:101258881 G>A), RS1001435451 (2:101256519 G>T)

Disease associations

OMIM: gene MIM:620509 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010151_4	Carotid intima media thickness x smoking interaction	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105958 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	3
aristolochic acid I	decreases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	increases abundance, affects cotreatment, affects expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012564	Binding	Binding affinity to CCR4-NOT transcription complex subunit 11 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

Clinical trials (associated diseases)

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