CNOT12

Summary

CNOT12 (CCR4-NOT transcription complex subunit 12, HGNC:19081) is a protein-coding gene on chromosome 11q12.1, encoding 182 kDa tankyrase-1-binding protein (Q9C0C2).

Enables ankyrin repeat binding activity; enzyme binding activity; and protein serine/threonine kinase activator activity. Involved in cellular response to ionizing radiation and double-strand break repair. Located in several cellular components, including adherens junction; heterochromatin; and nucleus. Part of CCR4-NOT complex.

Source: NCBI Gene 85456 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 320 total (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 21 tissues, sQTL in 7 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• MANE Select transcript: NM_033396
• Interaction hub: 1,826 STRING partners (top 9% of genes corpus-wide)
• Notable: 320 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19081
Approved symbol	CNOT12
Name	CCR4-NOT transcription complex subunit 12
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	TAB182, KIAA1741, FLJ45975
Ensembl gene	ENSG00000149115
Ensembl biotype	protein_coding
OMIM	607104
Entrez	85456

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000358252

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

ENST00000358252, ENST00000427750, ENST00000527207, ENST00000528882, ENST00000530920, ENST00000532273, ENST00000532437, ENST00000873604, ENST00000931552, ENST00000931553, ENST00000963512, ENST00000963513, ENST00000963514, ENST00000963515, ENST00000963516, ENST00000963517, ENST00000978787, ENST00001042153, ENST00001042155, ENST00001042156, ENST00001088696, ENST00001115276, ENST00001138811

RefSeq mRNA: 1 — MANE Select: NM_033396 NM_033396

CCDS: CCDS7951

Canonical transcript exons

ENST00000358252 — 12 exons

Exon	Start	End
ENSE00000988897	57302459	57302825
ENSE00001027119	57308395	57310556
ENSE00001610511	57320079	57320712
ENSE00002156509	57299642	57300081
ENSE00002200626	57324840	57324952
ENSE00002212871	57321792	57321950
ENSE00003529427	57300528	57300600
ENSE00003567035	57301807	57301943
ENSE00003582955	57300884	57301041
ENSE00003627317	57302074	57302224
ENSE00003665769	57317818	57317887
ENSE00003677407	57312534	57313889

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.1915 / max 332.0638, expressed in 1777 samples.

Highest expression (Bgee): lower esophagus mucosa, mucosa of stomach, skin of abdomen, skin of leg, ectocervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNOT12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.2e-29	+0.40	11:57317739:G:A
Spleen	eqtl	4.4e-14	+0.30	11:57311480:C:T
Stomach	eqtl	9.6e-08	-0.23	11:57247283:A:G
Lung	eqtl	1.9e-07	+0.13	11:57242940:C:A
Skin Not Sun Exposed Suprapubic	eqtl	3.5e-05	+0.11	11:57289419:G:A
Spleen	sqtl	5.7e-05	+0.62	11:57311997:A:G
Nerve Tibial	eqtl	7.5e-05	+0.12	11:57325294:A:G
Adipose Visceral Omentum	eqtl	1.1e-04	-0.29	11:57278408:T:G
Cells Cultured fibroblasts	sqtl	2.0e-04	-0.76	11:57342542:G:A
Cells EBV-transformed lymphocytes	eqtl	2.4e-04	-0.47	11:57179077:G:A
Skin Sun Exposed Lower leg	eqtl	4.0e-04	+0.07	11:57292341:A:G
Brain Cerebellum	eqtl	4.2e-04	-0.47	11:57337772:G:A
Thyroid	eqtl	4.8e-04	-0.13	11:57339055:G:C
Esophagus Muscularis	eqtl	8.6e-04	+0.08	11:57237593:T:C
Colon Transverse	eqtl	1.0e-03	+0.20	11:57250083:T:C
Stomach	sqtl	1.6e-03	-0.44	11:57309990:T:C
Muscle Skeletal	eqtl	2.2e-03	+0.10	11:57325294:A:G
Artery Tibial	eqtl	2.8e-03	-0.26	11:57265528:G:A
Skin Sun Exposed Lower leg	sqtl	3.6e-03	+0.40	11:56963751:C:T
Adipose Subcutaneous	eqtl	3.8e-03	+0.11	11:57223718:T:C

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
119724	21.2006	1750
119723	8.6619	1229
119716	2.8263	1133
119717	0.9052	604
119720	0.6848	429
119722	0.4079	222
119721	0.3048	172
119725	0.1298	59
119718	0.0701	23

Top tissues by expression

showing 100 of 247 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.05	gold quality
mucosa of stomach	UBERON:0001199	98.70	gold quality
skin of abdomen	UBERON:0001416	98.69	gold quality
skin of leg	UBERON:0001511	98.65	gold quality
ectocervix	UBERON:0012249	98.10	gold quality
omental fat pad	UBERON:0010414	98.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.99	gold quality
endocervix	UBERON:0000458	97.97	gold quality
peritoneum	UBERON:0002358	97.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.95	gold quality
body of stomach	UBERON:0001161	97.94	gold quality
lower esophagus	UBERON:0013473	97.94	gold quality
minor salivary gland	UBERON:0001830	97.89	gold quality
right coronary artery	UBERON:0001625	97.84	gold quality
right lobe of liver	UBERON:0001114	97.83	gold quality
upper lobe of left lung	UBERON:0008952	97.77	gold quality
right lung	UBERON:0002167	97.74	gold quality
esophagus	UBERON:0001043	97.68	gold quality
left coronary artery	UBERON:0001626	97.64	gold quality
left uterine tube	UBERON:0001303	97.63	gold quality
adenohypophysis	UBERON:0002196	97.60	gold quality
esophagus mucosa	UBERON:0002469	97.54	gold quality
tibial nerve	UBERON:0001323	97.53	gold quality
body of uterus	UBERON:0009853	97.48	gold quality
right ovary	UBERON:0002118	97.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.46	gold quality
popliteal artery	UBERON:0002250	97.44	gold quality
tibial artery	UBERON:0007610	97.44	gold quality
left adrenal gland cortex	UBERON:0035825	97.34	gold quality
right adrenal gland	UBERON:0001233	97.27	gold quality
left adrenal gland	UBERON:0001234	97.24	gold quality
right adrenal gland cortex	UBERON:0035827	97.24	gold quality
aorta	UBERON:0000947	97.22	gold quality
left lobe of thyroid gland	UBERON:0001120	97.21	gold quality
ascending aorta	UBERON:0001496	97.16	gold quality
right lobe of thyroid gland	UBERON:0001119	97.13	gold quality
thoracic aorta	UBERON:0001515	97.12	gold quality
apex of heart	UBERON:0002098	97.08	gold quality
colonic epithelium	UBERON:0000397	97.04	gold quality
coronary artery	UBERON:0001621	97.02	gold quality
left ovary	UBERON:0002119	96.89	gold quality
descending thoracic aorta	UBERON:0002345	96.84	gold quality
stomach	UBERON:0000945	96.56	gold quality
upper lobe of lung	UBERON:0008948	96.56	gold quality
zone of skin	UBERON:0000014	96.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.46	gold quality
stromal cell of endometrium	CL:0002255	96.45	gold quality
metanephros cortex	UBERON:0010533	96.44	gold quality
body of pancreas	UBERON:0001150	96.39	gold quality
adrenal cortex	UBERON:0001235	96.34	gold quality
uterine cervix	UBERON:0000002	96.31	gold quality
mouth mucosa	UBERON:0003729	96.21	gold quality
saliva-secreting gland	UBERON:0001044	96.18	gold quality
thyroid gland	UBERON:0002046	95.99	gold quality
upper arm skin	UBERON:0004263	95.95	gold quality
transverse colon	UBERON:0001157	95.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.77	gold quality
sural nerve	UBERON:0015488	95.75	gold quality
gastrocnemius	UBERON:0001388	95.71	gold quality
pituitary gland	UBERON:0000007	95.68	gold quality
adrenal gland	UBERON:0002369	95.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.46	gold quality
right uterine tube	UBERON:0001302	95.41	gold quality
mucosa of transverse colon	UBERON:0004991	95.36	gold quality
right atrium auricular region	UBERON:0006631	95.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.22	gold quality
vagina	UBERON:0000996	95.19	gold quality
muscle of leg	UBERON:0001383	94.78	gold quality
fundus of stomach	UBERON:0001160	94.38	gold quality
cardiac atrium	UBERON:0002081	94.34	gold quality
gall bladder	UBERON:0002110	94.17	gold quality
smooth muscle tissue	UBERON:0001135	94.05	gold quality
adipose tissue	UBERON:0001013	93.96	gold quality
pancreas	UBERON:0001264	93.76	gold quality
prostate gland	UBERON:0002367	93.61	gold quality
small intestine	UBERON:0002108	93.60	gold quality
heart left ventricle	UBERON:0002084	93.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.86	gold quality
ganglionic eminence	UBERON:0004023	92.63	gold quality
cardiac ventricle	UBERON:0002082	92.52	gold quality
ovary	UBERON:0000992	92.49	gold quality
colon	UBERON:0001155	92.44	gold quality
spleen	UBERON:0002106	92.40	gold quality
heart	UBERON:0000948	92.28	gold quality
right frontal lobe	UBERON:0002810	92.24	gold quality
intestine	UBERON:0000160	92.07	gold quality
amygdala	UBERON:0001876	91.85	gold quality
ventricular zone	UBERON:0003053	91.81	gold quality
large intestine	UBERON:0000059	91.79	gold quality
putamen	UBERON:0001874	91.72	gold quality
myometrium	UBERON:0001296	91.61	gold quality
right testis	UBERON:0004534	91.61	gold quality
nucleus accumbens	UBERON:0001882	91.58	gold quality
lung	UBERON:0002048	91.57	gold quality
left testis	UBERON:0004533	91.19	gold quality
caudate nucleus	UBERON:0001873	91.12	gold quality
cortex of kidney	UBERON:0001225	91.08	gold quality
anterior cingulate cortex	UBERON:0009835	91.08	gold quality
calcaneal tendon	UBERON:0003701	91.03	gold quality
urinary bladder	UBERON:0001255	90.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.61
E-GEOD-99795	no	102.45

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	78.3	high
Adipose tissue	tissue	58.8	medium
Stomach 1	tissue	49.8	medium
Esophagus	tissue	49.3	high
Vagina	tissue	48.5	high
Choroid plexus	tissue	47.4
Salivary gland	tissue	41.7	medium
Seminal vesicle	tissue	37.9	high
Cervix	tissue	34.8	medium
Lung	tissue	34.2	high
Putamen	tissue	31.5
Prostate	tissue	31.5	high
Medulla oblongata	tissue	31.3
Hippocampus	tissue	30.7	low
Urinary bladder	tissue	29.7	high
Liver	tissue	29.6	medium
Pancreas	tissue	29.2	medium
Epididymis	tissue	28.6	high
Nucleus accumbens	tissue	28.0
Tongue	tissue	27.8
Placenta	tissue	27.7	high
Smooth muscle	tissue	27.5	medium
Duodenum	tissue	27.1	medium
Gallbladder	tissue	26.4	high
Endometrium 1	tissue	26.2	medium
Retrosplenial cortex	tissue	26.0
Ovary	tissue	25.9	medium
Hippocampal formation	tissue	25.9
Adrenal gland	tissue	25.8	medium
Substantia nigra	tissue	25.2
Small intestine	tissue	25.0	medium
Locus coeruleus	tissue	24.1
Fallopian tube	tissue	22.5	high
Breast	tissue	22.1	high
Colon	tissue	21.8	high
Thyroid gland	tissue	21.7	medium
Skeletal muscle	tissue	21.5	low
Spinal cord	tissue	21.2
Cerebral cortex	tissue	20.9	medium
Frontal cortex	tissue	20.9
Thymus	tissue	20.8
Occipital cortex	tissue	20.8
Retrosplenial and cingulate cortex	tissue	20.7
Entorhinal cortex	tissue	19.8
Amygdala	tissue	18.3
Postcentral gyrus	tissue	18.1
Parathyroid gland	tissue	17.8	not detected
Somatosensory cortex	tissue	17.4
Pituitary gland	tissue	17.1
Spleen	tissue	17.0	low
Appendix	tissue	16.3	medium
Rectum	tissue	15.2	high
Heart muscle	tissue	14.8	low
Tonsil	tissue	13.4	high
Basal ganglia	tissue	12.4	low
Ventral forebrain	tissue	12.4
Kidney	tissue	11.5	high
Hypothalamus	tissue	11.4
Olfactory bulb	tissue	11.0
Septum	tissue	10.4

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Blood vessel (52.2), Basal amygdala (35.1), Posterior thalamic nucleus (34.5), Central amygdala (34.3), Hippocampus, CA3 (34.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CNOT12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 83 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
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-3119	99.92	71.34	2390
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.438, missense Z 0.827 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000358252 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 13)

• The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182). (PMID:11854288)
• Identification of a tankyrase-binding motif in this protein. (PMID:12080061)
• Data show that tankyrase 1 inhibition in human cancer cells enhances telomere shortening by a telomerase inhibitor and hastens cell death. (PMID:15652747)
• We also demonstrate a requirement for tankyrase-1 in the assembly of bipolar spindles, and identify the spindle-pole protein NuMA as a substrate for covalent modification by tankyrase-1. (PMID:16244666)
• TNKS-1 mRNA in urine sediment from patients with bladder TCC correlated with tumor stage, and higher preoperative levels were associated with increased risk of early recurrence. (PMID:17617028)
• TNKS1BP1 has a role in DNA double-strand break repair though DNA-PKcs autophosphorylation which is dependent on PARP-1 (PMID:25749521)
• Results found that TNKS1BP1 was upregulated in human lung adenocarcinoma tissues, and regulates genome stability, mainly through affecting the homologous recombination pathway of DNA double-strand breaks. These results indicate that overexpression of TNKS1BP1 might affect the outcomes of lung cancer patients to chemotherapy and radiotherapy. (PMID:28058814)
• In clinical samples of pancreatic cancer, TNKS1BP1 expression was reduced in invasive regions. We propose that the tankyrase-TNKS1BP1 axis constitutes a posttranslational modulator of cell invasion whose aberration promotes cancer malignancy (PMID:28202517)
• Tissue-Specific Regulation of the Wnt/beta-Catenin Pathway by PAGE4 Inhibition of Tankyrase. (PMID:32698014)
• TCF3-activated FAM201A enhances cell proliferation and invasion via miR-186-5p/TNKS1BP1 axis in triple-negative breast cancer. (PMID:33011533)
• TAB182 aggravates progression of esophageal squamous cell carcinoma by enhancing beta-catenin nuclear translocation through FHL2 dependent manner. (PMID:36289198)
• Silencing TAB182 inhibits cell EMT, migration and invasion by downregulating EGFR in A549 NSCLC cells. (PMID:36689051)
• Downregulation of TAB182 promotes cancer stem-like cell properties and therapeutic resistance in triple-negative breast cancer cells. (PMID:37953246)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnks1bp1	ENSMUSG00000033955
rattus_norvegicus	Tnks1bp1	ENSRNOG00000009195

Paralogs (1): KIAA1671 (ENSG00000197077)

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
Gallus gallus	Q5ZJ26	65.9%	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
APLNR	protein-coding	187
LRRC55	protein-coding	219527
SSRP1	protein-coding	6749
PRG3	protein-coding	10394
P2RX3	protein-coding	5024
PRG2	protein-coding	5553

Protein

Protein identifiers

182 kDa tankyrase-1-binding protein — Q9C0C2 (reviewed: Q9C0C2)

All UniProt accessions (5): A0A024R542, A0A2R8Y5C4, E9PKE7, E9PKK0, Q9C0C2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Binds to the ANK repeat domain of TNKS1 and TNKS2.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Chromosome.

Tissue specificity. Detected in testis, ovary, lung, skeletal muscle, heart, prostate and pancreas, and at very low levels in brain and peripheral blood leukocytes.

Post-translational modifications. ADP-ribosylated by TNKS1 (in vitro).

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0C2-1	1	yes
Q9C0C2-2	2

RefSeq proteins (1): NP_203754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032764	Tankyrase-bd_C	Domain
IPR040006	TNKS1BP1-like	Family

Pfam: PF15327

UniProt features (121 total): modified residue 79, compositionally biased region 19, region of interest 10, sequence conflict 5, splice variant 3, short sequence motif 2, sequence variant 2, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0C2-F1	38.50	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF approved

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 (79)

Type	Positions
Phosphoserine	1533, 1545, 1558, 1620, 1621, 1631, 1652, 1666, 1715, 14, 178, 221, 228, 287, 301, 429, 435, 437, 494, 498, 601, 672, 691, 695, 712, 724, 744, 762, 806, 836, 851, 872, 877, 882, 893, 899, 920, 936, 976, 983 … (+29)
Phosphothreonine	1563, 131, 239, 501, 833, 979, 1282, 1518
N6-methyllysine	1644
Phosphotyrosine	897

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: 195 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, EFC_Q6, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (4): nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), double-strand break repair (GO:0006302), telomere maintenance via telomerase (GO:0007004), cellular response to ionizing radiation (GO:0071479)

GO Molecular Function (6): enzyme binding (GO:0019899), protein serine/threonine kinase activator activity (GO:0043539), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), ankyrin repeat binding (GO:0071532), protein binding (GO:0005515)

GO Cellular Component (8): heterochromatin (GO:0000792), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), adherens junction (GO:0005912), CCR4-NOT complex (GO:0030014), chromosome (GO:0005694)

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

23 GO namespaces:

Category	Terms
binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
DNA repair	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
response to ionizing radiation	1
cellular response to radiation	1
protein binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
cell adhesion molecule binding	1
protein domain specific binding	1
chromatin	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-cell junction	1
intracellular protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to ionizing radiation	BP	mutant phenotype
double-strand break repair	BP	mutant phenotype
CCR4-NOT complex	CC	direct assay
adherens junction	CC	direct assay
cytoplasm	CC	direct assay
heterochromatin	CC	direct assay
nucleus	CC	direct assay
ankyrin repeat binding	MF	mutant phenotype
cadherin binding	MF	high-throughput assay
enzyme binding	MF	direct assay
protein serine/threonine kinase activator activity	MF	mutant phenotype
protein-containing complex binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,826 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT12	TNKS	O95271	893
CNOT12	TNKS2	Q9H2K2	817
CNOT12	TERF1	P54274	788
CNOT12	FNBP1	Q96RU3	764
CNOT12	LNPEP	Q9UIQ6	697
CNOT12	ELL	P55199	601
CNOT12	MCL1	Q07820	556
CNOT12	SNX2	P82862	552
CNOT12	ANK3	Q12955	542
CNOT12	SERPINE2	P07093	490
CNOT12	MLLT1	Q03111	487
CNOT12	PARP1	P09874	480
CNOT12	CNOT9	Q92600	458
CNOT12	AXIN1	O15169	443
CNOT12	CNOT11	Q9UKZ1	442

SIGNOR signaling

showing 2 of 3 signaling interactions:

A	Effect	B	Mechanism
TNKS1BP1	“form complex”	“CCR4-NOT complex”	binding
MAPK1	unknown	TNKS1BP1	phosphorylation

Protein complexes (CORUM) (4)

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

4 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

Disease & clinical

Genetic variants

Variant evidence for CNOT12: 320 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	281
Likely benign	14
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,251):

Position(s)	Effect	Δscore	Sites
11:57300526–57300527	donor_loss	1.0000	5
11:57300925	donor_gain	1.0000
11:57301805–57301806	donor_loss	1.0000	4
11:57301944–57301945	acceptor_loss	1.0000	5
11:57302072–57302073	donor_loss	1.0000	3
11:57321790–57321791	donor_loss	1.0000	4
11:57300601–57300602	acceptor_loss	0.9900	5
11:57300614	acceptor_gain	0.9900
11:57301042–57301043	acceptor_loss	0.9900	5
11:57301056	acceptor_gain	0.9900

AlphaMissense

1,364 missense substitutions predicted likely pathogenic (of 11,167 scored), across 369 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
M81	9	0.831	0.993
F1648	8	0.955	0.989
D1567	8	0.944	0.978
F476	8	0.929	0.990
D1562	8	0.861	0.957
N82	8	0.858	0.982
D727	8	0.853	0.911
W1718	7	0.991	0.999
W478	7	0.974	0.997
W723	7	0.974	0.995
F732	7	0.960	0.990
W470	7	0.954	0.991
C1690	7	0.930	0.981
W684	7	0.927	0.982
K80	7	0.926	0.996
F480	7	0.921	0.981
F189	7	0.920	0.984
F1607	7	0.905	0.971
F149	7	0.884	0.974
F1559	7	0.884	0.974

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
Liver Hepatocellular Carcinoma (validation)	favorable	0.000443
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000685

Disease associations

OMIM: gene MIM:607104 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST010241_120	Apolipoprotein A1 levels	9e-13
GCST90002397_134	Mean spheric corpuscular volume	4e-12
GCST012100_13	Hypertrophic cardiomyopathy (sarcomere positive)	2e-6
GCST009391_810	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0010394	sphingomyelin 18:1 measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295939 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 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

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.19	nM	CHEMBL5653589
7.25	ED50	56.19	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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	2149627: Binding affinity to human TNKS1BP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0562	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
Cisplatin	decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
sodium arsenate	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	decreases expression, affects reaction	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118960	Binding	Binding affinity to TNKS1BP1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2J8	Abcam HeLa TNKS1BP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

5 trials:

NCT	Phase	Status	Title
NCT03600649	Phase 1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	Phase 1/2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	Phase 1/2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	Phase 1/2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CNOT12 across ~30M SureChEMBL compounds — explore on Sugi Predict.