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 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 319 total
• Druggable target: yes
• MANE Select transcript: NM_033396

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: 16 — 13 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000358252, ENST00000427750, ENST00000527207, ENST00000528882, ENST00000530920, ENST00000532273, ENST00000532437, ENST00000873604, ENST00000931552, ENST00000931553, ENST00000963512, ENST00000963513, ENST00000963514, ENST00000963515, ENST00000963516, ENST00000963517

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.

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

247 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting CNOT12, 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-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

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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-9i23.6	ENSDARG00000094678
mus_musculus	Tnks1bp1	ENSMUSG00000033955
rattus_norvegicus	Tnks1bp1	ENSRNOG00000009195

Paralogs (1): KIAA1671 (ENSG00000197077)

Protein

Protein identifiers

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

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

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 1533, 1545, 1558, 1563, 1620, 1621, 1631, 1644, 1652, 1666, 1715, 14, 131, 178, 221, 228, 239, 287, 301, 429 …

Function

Pathways and Gene Ontology

Reactome pathways

12 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
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-429914	Deadenylation-dependent mRNA decay
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA
R-HSA-9816359	Maternal to zygotic transition (MZT)

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

Rollup of top-9 pathways:

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

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT12	TNKS	O95271	983
CNOT12	TNKS2	Q9H2K2	926
CNOT12	TERF1	P54274	867
CNOT12	LNPEP	Q9UIQ6	802
CNOT12	CNOT9	Q92600	779
CNOT12	FNBP1	Q96RU3	741
CNOT12	CNOT10	Q9H9A5	714
CNOT12	MCL1	Q07820	690
CNOT12	CNOT11	Q9UKZ1	682
CNOT12	CNOT3	O75175	664
CNOT12	CNOT1	A5YKK6	635
CNOT12	CNOT2	Q9NZN8	623
CNOT12	NUMA1	Q14980	611
CNOT12	CNOT7	Q9UIV1	588
CNOT12	CNOT6L	Q96LI5	580

IntAct

149 interactions, top by confidence:

A	B	Type	Score
CNOT7	CNOT1	psi-mi:“MI:0914”(association)	0.880
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
CNOT6L	TNKS1BP1	psi-mi:“MI:0915”(physical association)	0.660
TNKS1BP1	TOB1	psi-mi:“MI:0914”(association)	0.640
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
TNKS1BP1	FHL2	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (234): TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Co-fractionation), TNKS1BP1 (Co-fractionation), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A2TJV2, A4FU49, A6NDB9, A6X8Z5, D3ZAQ5, P0C671, P10636, P10637, P48681, P58871, Q14676, Q2YDF7, Q3MI48, Q4R729, Q5EBJ4, Q5PSV9, Q5S6V2, Q5SWP3, Q5TM66, Q5TM68, Q5U2M8, Q5YCV9, Q5YCW0, Q5YCW1, Q640N3, Q68A65, Q68DA7, Q6NYC8, Q6ZW13, Q767L8, Q7YR40, Q7Z6I6, Q811Q2, Q8BHB9, Q8BHW6, Q8BQ30, Q8CB87, Q8CC96, Q8IXJ9

Diamond homologs: P58871, Q5ZJ26, Q8BRV5, Q9BY89, Q9C0C2

SIGNOR signaling

3 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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	8	59.3×	1e-10
Deadenylation of mRNA	8	50.2×	3e-10
M-decay: degradation of maternal mRNAs by maternally stored factors	9	42.0×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	8	63.6×	2e-10
regulatory ncRNA-mediated gene silencing	6	40.0×	2e-06
negative regulation of translation	7	13.6×	1e-04
regulation of translation	6	13.0×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

319 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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2362 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57300522:CCTCA:C	donor_loss	1.0000
11:57300523:CTCA:C	donor_loss	1.0000
11:57300524:TCA:T	donor_loss	1.0000
11:57300525:CA:C	donor_loss	1.0000
11:57300526:A:AG	donor_loss	1.0000
11:57300925:T:A	donor_gain	1.0000
11:57301803:GTAC:G	donor_loss	1.0000
11:57301805:A:AT	donor_loss	1.0000
11:57301806:CCT:C	donor_loss	1.0000
11:57301939:TGGCT:T	acceptor_gain	1.0000
11:57301940:GGCT:G	acceptor_gain	1.0000
11:57301941:GCTC:G	acceptor_loss	1.0000
11:57301942:CT:C	acceptor_gain	1.0000
11:57301943:TCTGC:T	acceptor_loss	1.0000
11:57301944:C:A	acceptor_loss	1.0000
11:57301944:C:CC	acceptor_gain	1.0000
11:57301945:T:G	acceptor_loss	1.0000
11:57302070:CTAC:C	donor_loss	1.0000
11:57302071:TACC:T	donor_loss	1.0000
11:57302073:C:CA	donor_loss	1.0000
11:57317816:A:AC	donor_gain	1.0000
11:57317817:C:CC	donor_gain	1.0000
11:57317817:CAT:C	donor_gain	1.0000
11:57321789:TAC:T	donor_loss	1.0000
11:57321790:ACC:A	donor_loss	1.0000
11:57321791:CCTGG:C	donor_gain	1.0000
11:57324834:A:AC	donor_gain	1.0000
11:57324835:C:CC	donor_gain	1.0000
11:57324838:A:AC	donor_gain	1.0000
11:57324839:C:CA	donor_gain	1.0000

AlphaMissense

11167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57300578:A:G	W1718R	0.999
11:57300578:A:T	W1718R	0.999
11:57300576:C:A	W1718C	0.998
11:57300576:C:G	W1718C	0.998
11:57313256:A:G	W478R	0.997
11:57313256:A:T	W478R	0.997
11:57320567:C:A	K80N	0.996
11:57320567:C:G	K80N	0.996
11:57310544:A:G	W723R	0.995
11:57310544:A:T	W723R	0.995
11:57320556:A:G	L84P	0.994
11:57320565:A:G	M81T	0.993
11:57300555:C:A	K1725N	0.992
11:57300555:C:G	K1725N	0.992
11:57313254:C:A	W478C	0.992
11:57313254:C:G	W478C	0.992
11:57300565:A:G	L1722P	0.991
11:57310542:C:A	W723C	0.991
11:57310542:C:G	W723C	0.991
11:57313280:A:G	W470R	0.991
11:57313280:A:T	W470R	0.991
11:57300940:C:A	K1691N	0.990
11:57300940:C:G	K1691N	0.990
11:57300949:T:A	K1688N	0.990
11:57300949:T:G	K1688N	0.990
11:57301807:C:A	K1657N	0.990
11:57301807:C:G	K1657N	0.990
11:57310515:A:C	F732L	0.990
11:57310515:A:T	F732L	0.990
11:57310517:A:G	F732L	0.990

dbSNP variants (sampled 300 via entrez): RS1000116445 (11:57311623 C>T), RS1000123600 (11:57316132 A>T), RS1000226550 (11:57314871 T>C), RS1000252545 (11:57311442 C>A,T), RS1000368828 (11:57299475 T>C), RS1000436354 (11:57316376 A>C), RS1000478300 (11:57321383 C>A,T), RS1000531959 (11:57316413 C>A), RS1000610862 (11:57299846 G>A), RS1000808448 (11:57322535 C>A,T), RS1000879889 (11:57306012 G>T), RS1000966195 (11:57316139 G>A), RS1001092400 (11:57321176 C>T), RS1001468049 (11:57315371 C>T), RS1001480369 (11:57299604 G>C,T)

Disease associations

OMIM: gene MIM:607104 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_785	Metabolite levels	9.000000e-06
GCST010241_95	Apolipoprotein A1 levels	9.000000e-13
GCST012100_12	Hypertrophic cardiomyopathy (sarcomere positive)	2.000000e-06
GCST90002397_524	Mean spheric corpuscular volume	4.000000e-12

EFO canonical traits (2, from GWAS)

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

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295939 (SINGLE PROTEIN)

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

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	increases abundance, increases expression, decreases 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	affects cotreatment, decreases expression	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)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	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	PHASE1/PHASE2	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