CTNNB1

Summary

CTNNB1 (catenin beta 1, HGNC:2514) is a protein-coding gene on chromosome 3p22.1, encoding Catenin beta-1 (P35222). Key downstream component of the canonical Wnt signaling pathway. In precision oncology, CTNNB1 S45F confers sensitivity to Imatinib in Desmoid Tumor (CIViC Level B); 5 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 12.3% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1499 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 951 total — 172 pathogenic, 56 likely-pathogenic
• Phenotypes (HPO): 256
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 6 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 20 cancer types
• Cancer dependency (DepMap): dependent in 12.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 345 downstream targets (CollecTRI)
• MANE Select transcript: NM_001904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2514
Approved symbol	CTNNB1
Name	catenin beta 1
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	beta-catenin, armadillo
Ensembl gene	ENSG00000168036
Ensembl biotype	protein_coding
OMIM	116806
Entrez	1499

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 54 protein_coding, 10 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000349496, ENST00000396183, ENST00000396185, ENST00000405570, ENST00000426215, ENST00000431914, ENST00000433400, ENST00000441708, ENST00000450969, ENST00000453024, ENST00000465552, ENST00000471014, ENST00000482042, ENST00000485265, ENST00000488914, ENST00000642248, ENST00000642315, ENST00000642426, ENST00000642836, ENST00000642886, ENST00000642986, ENST00000642992, ENST00000643031, ENST00000643052, ENST00000643297, ENST00000643541, ENST00000643865, ENST00000643977, ENST00000643992, ENST00000644138, ENST00000644395, ENST00000644501, ENST00000644524, ENST00000644678, ENST00000644867, ENST00000644873, ENST00000644906, ENST00000645210, ENST00000645276, ENST00000645305, ENST00000645320, ENST00000645493, ENST00000645763, ENST00000645900, ENST00000645927, ENST00000645982, ENST00000646074, ENST00000646116, ENST00000646174, ENST00000646369, ENST00000646381, ENST00000646725, ENST00000647021, ENST00000647264, ENST00000647390, ENST00000647413, ENST00000715148, ENST00000715149, ENST00000715150, ENST00000715151, ENST00000715152, ENST00000715153, ENST00000715155, ENST00000910212, ENST00000910213, ENST00000910214, ENST00000910215, ENST00000932556, ENST00000968440, ENST00000968441, ENST00000968442

RefSeq mRNA: 4 — MANE Select: NM_001904 NM_001098209, NM_001098210, NM_001330729, NM_001904

CCDS: CCDS2694, CCDS87067

Canonical transcript exons

ENST00000349496 — 15 exons

Exon	Start	End
ENSE00001592339	41234139	41234297
ENSE00001643204	41225660	41225861
ENSE00001649367	41233341	41233444
ENSE00001692569	41225334	41225572
ENSE00001718373	41233529	41233867
ENSE00001767208	41227208	41227352
ENSE00001782706	41236588	41236709
ENSE00001805633	41238016	41238076
ENSE00001933873	41199505	41199670
ENSE00003464041	41224526	41224753
ENSE00003521934	41236349	41236499
ENSE00003554494	41224021	41224081
ENSE00003558822	41235724	41235843
ENSE00003593193	41224954	41225207
ENSE00004025924	41239134	41240443

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 293.2582 / max 2898.3686, expressed in 1829 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36206	222.0188	1829
36205	27.0816	1818
36222	25.7589	1749
36221	6.1439	1624
36209	4.4475	756
36219	1.9862	820
36204	1.5067	1064
36216	1.2141	753
36208	0.8712	305
36217	0.7513	450

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.58	gold quality
ventricular zone	UBERON:0003053	99.42	gold quality
periodontal ligament	UBERON:0008266	99.27	gold quality
calcaneal tendon	UBERON:0003701	99.22	gold quality
stromal cell of endometrium	CL:0002255	99.09	gold quality
seminal vesicle	UBERON:0000998	99.07	gold quality
endocervix	UBERON:0000458	99.04	gold quality
blood vessel layer	UBERON:0004797	99.03	gold quality
ganglionic eminence	UBERON:0004023	98.85	gold quality
right ovary	UBERON:0002118	98.77	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.73	gold quality
colonic epithelium	UBERON:0000397	98.70	gold quality
left ovary	UBERON:0002119	98.70	gold quality
ectocervix	UBERON:0012249	98.67	gold quality
popliteal artery	UBERON:0002250	98.66	gold quality
tibial artery	UBERON:0007610	98.66	gold quality
gall bladder	UBERON:0002110	98.57	gold quality
body of uterus	UBERON:0009853	98.56	gold quality
right uterine tube	UBERON:0001302	98.52	gold quality
rectum	UBERON:0001052	98.51	gold quality
cerebellar cortex	UBERON:0002129	98.49	gold quality
cerebellar hemisphere	UBERON:0002245	98.49	gold quality
right lobe of thyroid gland	UBERON:0001119	98.45	gold quality
upper lobe of left lung	UBERON:0008952	98.43	gold quality
left uterine tube	UBERON:0001303	98.41	gold quality
cerebellum	UBERON:0002037	98.40	gold quality
tibial nerve	UBERON:0001323	98.37	gold quality
left lobe of thyroid gland	UBERON:0001120	98.32	gold quality
right lung	UBERON:0002167	98.32	gold quality
upper lobe of lung	UBERON:0008948	98.31	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	3042.14
E-HCAD-24	yes	2065.08
E-MTAB-8271	yes	1518.56
E-MTAB-5061	yes	6.35
E-ENAD-21	no	2297.84
E-HCAD-13	no	1669.95
E-GEOD-76312	no	1318.33
E-MTAB-8205	no	1035.55
E-MTAB-6911	no	788.48
E-MTAB-8894	no	584.45
E-MTAB-6524	no	422.27
E-MTAB-6108	no	400.14
E-MTAB-7303	no	63.82
E-CURD-114	no	20.06
E-GEOD-93593	no	16.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

345 targets.

Target	Regulation
AATF	Repression
ABCB1	Activation
ADAM2	Repression
ADGRG2	Activation
AFF3	Activation
AKAP13	Activation
AKT1	Activation
AKT2	Activation
ALDH1A1	Activation
ALDH3A2	Activation
AMHR2	Activation
APCDD1	Activation
APOD	Activation
APP	Repression
AR	Unknown
ARHGAP26	Activation
ARL4A	Activation
ASCL1	Activation
ASNS	Activation
ATOH1	Activation
AXIN2	Activation
BACE1	Repression
BAG2	Repression
BAG3	Repression
BAMBI	Activation
BCL2	Activation
BCL2L1	Activation
BCL2L2	Activation
BGLAP	Repression
BIK	Activation

Upstream regulators (CollecTRI, top): AP1, AR, ATF4, BCL11B, CDH3, CREB1, CTNNB1, E2F1, EGR1, EN1, ESR1, FOXC2, FOXM1, GLI1, GLI2, GLI3, HNF1A, HNF4A, ID1, IRF3, IRF6, JUN, KLF4, LEF1, MEF2C, MEST, MYH9, NELFCD, NFKB, NKX2-5, NR2F2, PAX1, PAX5, PDX1, PLAG1, PPARG, RXRA, RXRB, SATB1, SIRT1

miRNA regulators (miRDB)

82 targeting CTNNB1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 12.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Loss of beta-catenin may result in the disruption of the function of the cell-cell adhesion complex, which may cause weak cell-cell adhesion and confer invasive properties on a tumor. (PMID:11747475)
• aardvark gene product (PMID:11790773)
• Abnormal beta-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China. (PMID:11819825)
• Beta-catenin might be related to the occurrence and development of kidney tumor. (PMID:11831984)
• Proof for the regulated phosphorylation of the Ser/Thr residues of beta-catenin by Wnt signaling. (PMID:11834740)
• No germline mutations of CTNNB1 have been identified nor linkage to chromosome 3p21 been demonstrated in 8 subjects with Birt-Hogg-Dube syndrome, suggesting that CTNNB1 should be excluded as a candidate gene for BHD. (PMID:11836379)
• Immunohistochemistry of cyclin D1 and beta-catenin, and mutational analysis of exon 3 of beta-catenin gene in parathyroid adenomas (PMID:11836555)
• Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival (PMID:11839663)
• The minimal necessary components of the androgen receptor and beta-catenin required for binding nuclear accumulation of beta-catenin nuclear import appears to be the DNA/ligand binding regions and the Armadillo repeats of beta-catenin (PMID:11856748)
• increased expression predicts favorable prognosis in resected nonsmall cell lung carcinoma (PMID:11857309)
• findings indicate that alterations of beta-catenin are frequent in cancer of the uterine cervix and suggest that they may play an important role in the development of these tumors (PMID:11893906)
• mutations rare in ulcerative colitis-related colorectal carcinomas (PMID:11920497)
• CTNNB1 signaling plays a critical role in the development of a significant fraction of prostate cancers. (PMID:11921277)
• One out of 62 melanoma cell lines was found to carry a mutation in exon 3 of the beta-catenin gene indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event (PMID:11930117)
• results imply that claudin-1 is involved in the beta-catenin-Tcf/LEF signaling pathway (PMID:11939410)
• Activation of AXIN2 expression by beta-catenin-T cell factor (PMID:11940574)
• ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas (PMID:11950845)
• nuclear beta-catenin expression significantly related to ulcerative growth of colorectal cancer (PMID:11953860)
• beta-catenin plays a role in endometrial carcinogenesis, particularly in endometrioid carcinomas (PMID:11957146)
• Arg(96) mutant has a dominant-negative effect on GSK-3beta-dependent phosphorylation of beta-catenin and targeting of beta-catenin for degradation requires prior priming through phosphorylation of Ser(45) (PMID:11967263)
• Protein kinase CK2 dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TRCp and enhances beta-catenin degradation [UBC3B] (PMID:12037680)
• results indicate selection for APC genotypes that are likely to retain some activity in downregulating beta-catenin signaling (PMID:12045208)
• wnt3a-beta catenin signaling regulates LEF-1 gene expression (PMID:12052822)
• targeted inactivation reveals effects of beta-catenin mutation (PMID:12060769)
• Mutation in exon 3 of the beta-catenin gene was found in 2 of the 20 endometrial cancer samples; however, it was not found in the 25 endometrial hyperplasias or the 20 associated hyperplasias. (PMID:12111402)
• Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. (PMID:12124804)
• Anticancer-drug-induced apoptotic cell death in leukemia cells is associated with proteolysis of beta-catenin. beta-Catenin plays a role in promoting Jurkat survival. (PMID:12127563)
• Regulation of leukemic cell adhesion, proliferation, and survival by beta-catenin. (PMID:12130512)
• oxidative stress induces tyrosine phosphorylation and cellular redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes by a tyrosine-kinase-dependent mechanism (PMID:12169098)
• Nr-CAM is the gene most extensively induced by beta catenin (PMID:12183361)
• data support the notion that upregulation of cyclin D1 and Fra-1 in human colorectal adenocarcinomas is driven by abnormally expressed beta-catenin; however, the regulation of c-myc expression in colorectal tumors appears to be more complex (PMID:12209953)
• Role of Wnt pathway in medulloblastoma oncogenesis: accumulation of beta-catenin in tumor cells was immunohistochemically proven in 5 cases; 2 cases showed positive immunoreactivity for Wnt-1 and another 2 showed mutation of either CTNNB1 or AXIN1 (PMID:12209999)
• Restoration of E-cadherin/beta-catenin expression in pancreatic cancer cells inhibits growth by induction of apoptosis. (PMID:12219004)
• Beta catenin induced human melanoma growth requires the downstream target Microphthalmia-associated transcription factor. (PMID:12235125)
• Presenilin couples beta-catenin phosphorylation through two sequential kinase activities independent of the Wnt-regulated Axin/CK1alpha complex. (PMID:12297048)
• beta-catenin, which participates in the Wnt signaling pathway, might play a more important role in the formation of hepatic adenoma than in that of focal nodular hyperplasia. (PMID:12297840)
• found a pattern of beta-catenin immunostaining in typical carcinoid tumors of the appendix that was different from the pattern seen in non-appendiceal carcinoid tumors (PMID:12389996)
• beta-catenin plays an important role in oncogenesis through the crossregulation of NF-kappa B in breast and colonic neoplasms (PMID:12398896)
• abnormal expression of beta-catenin in gastric carcinoma and survival (PMID:12452049)
• The aberrant expression of beta-catenin protein was statistically correlated to the lymph node metastasis in esophageal cancer. (PMID:12478897)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctnnb2	ENSDARG00000023472
mus_musculus	Ctnnb1	ENSMUSG00000006932
rattus_norvegicus	Ctnnb1	ENSRNOG00000054172

Paralogs (4): ANKAR (ENSG00000151687), ARMC3 (ENSG00000165309), ODAD2 (ENSG00000169126), JUP (ENSG00000173801)

Protein

Protein identifiers

Catenin beta-1 — P35222 (reviewed: P35222)

Alternative names: Beta-catenin

All UniProt accessions (19): A0A2R8Y543, A0A2R8Y5A3, A0A2R8Y5C3, P35222, A0A2R8Y5Z1, A0A2R8Y6G0, A0A2R8Y750, A0A2R8Y7Z0, A0A2R8Y804, A0A2R8Y815, A0A2R8YCH5, A0A2R8YG06, A0AAQ5BIA4, A0AAQ5BIB8, A0AAQ5BIB9, A0AAQ5BIC2, A0AAQ5BIC3, A0AAQ5BIC6, B4DGU4

UniProt curated annotations — full annotation on UniProt →

Function. Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Also acts as a coactivator for other transcription factors, such as NR5A2. Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle. Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4. Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts.

Subunit / interactions. Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin:catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds NHERF1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with SCRIB. Interacts with RAPGEF2. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain). Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of CDK5. Interacts with PTK6. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Interacts with FERMT2. Identified in a complex with TCF7L2/TCF4 and FERMT2. Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220. Interacts with CTNND2. Interacts (via the C-terminal region) with CBY1. The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at ‘Ser-9’). Interacts with DLG5. Interacts with FAM53B; promoting translocation to the nucleus. Interacts with TMEM170B. Interacts with AHI1. Interacts with GID8. Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1. Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2. Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1. Interacts with AMFR. Interacts with LMBR1L. Interacts with SOX30; prevents interaction of CTNNB1 with TCF7L2/TCF4 and leads to inhibition of Wnt signaling. Interacts with SOX9; inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling. Interacts with SPN/CD43 cytoplasmic tail. Interacts (when phosphorylated at Tyr-333) with isoform M2 of PKM (PKM2); promoting transcription activation. Interacts with PKP2 (via HEAD domain). Interacts with CDH1. Interacts (when unphosphorylated) with FLYWCH1, perhaps preventing interaction of CTNNB1 with TCF4, and thereby regulating transcription activation; phosphorylation of CTNNB1 may inhibit the interaction. Interacts (via the central armadillo domains) with probable transcriptional regulator ADNP (via N-terminal region); interaction is direct and stabilizes CTNNB1 by modulating its phosphorylation by glycogen synthase kinase-3 beta GSK3B. Interacts with NR5A2. Interacts with DSG2; the interaction promotes localization of CTNNB1 at cell junctions thus reducing its nuclear localization and subsequent transcription of CTNNB1/TCF-target genes. Interacts with FBXO16. (Microbial infection) Interacts with herpes virus 8 protein vPK; this interaction inhibits the Wnt signaling pathway.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Cell junction. Adherens junction. Cell membrane. Microtubule organizing center. Centrosome. Spindle pole. Synapse. Cilium basal body.

Tissue specificity. Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). Expressed in breast cancer tissues (at protein level).

Post-translational modifications. Phosphorylation at Ser-552 by AMPK promotes stabilization of the protein, enhancing TCF/LEF-mediated transcription. Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation. Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity. Phosphorylation by SRC at Tyr-333 promotes interaction with isoform M2 of PKM (PKM2); promoting transcription activation. Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation. Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation. Ubiquitinated and degraded following interaction with SOX9. Ubiquitinated via ‘Lys-11’- and ‘Lys-29’-linked ubiquitin chains by UBR5, leading to its stabilization. Ubiquitinated by the SCF-FBXO16 E3 ubiquitin ligase, leading to proteasomal degradation. S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions. O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1. Deacetylated at Lys-49 by SIRT1. Phosphorylated at Thr-556 by herpes virus 1/HHV-1 leading to CTNNB1 inhibition.

Disease relevance. Colorectal cancer (CRC) [MIM:114500] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. The gene represented in this entry may be involved in disease pathogenesis. Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. Pilomatrixoma (PTR) [MIM:132600] Common benign skin tumor. The gene represented in this entry is involved in disease pathogenesis. Medulloblastoma (MDB) [MIM:155255] Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. The gene represented in this entry may be involved in disease pathogenesis. Ovarian cancer (OC) [MIM:167000] The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1. Mesothelioma, malignant (MESOM) [MIM:156240] An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. The gene represented in this entry may be involved in disease pathogenesis. Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) [MIM:615075] An autosomal dominant disorder characterized by global developmental delay, severe intellectual disability with absent or very limited speech, microcephaly, spasticity, and visual abnormalities. The disease is caused by variants affecting the gene represented in this entry. Vitreoretinopathy, exudative 7 (EVR7) [MIM:617572] An autosomal dominant form of exudative vitreoretinopathy, a disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the beta-catenin family.

RefSeq proteins (4): NP_001091679, NP_001091680, NP_001317658, NP_001895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR013284	Beta-catenin	Family
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF00514

UniProt features (145 total): helix 41, sequence variant 27, mutagenesis site 22, modified residue 19, repeat 12, strand 8, turn 7, region of interest 5, initiator methionine 1, chain 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

50 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3FQN	X-RAY DIFFRACTION	1.65
3FQR	X-RAY DIFFRACTION	1.7
7AFW	X-RAY DIFFRACTION	1.81
1JDH	X-RAY DIFFRACTION	1.9
9I8K	X-RAY DIFFRACTION	2
9I8X	X-RAY DIFFRACTION	2
8RU3	X-RAY DIFFRACTION	2
6M90	X-RAY DIFFRACTION	2.05
1G3J	X-RAY DIFFRACTION	2.1
1T08	X-RAY DIFFRACTION	2.1
3DIW	X-RAY DIFFRACTION	2.1
8RU4	X-RAY DIFFRACTION	2.13
1QZ7	X-RAY DIFFRACTION	2.2
2Z6H	X-RAY DIFFRACTION	2.2
3SL9	X-RAY DIFFRACTION	2.2
6O9B	X-RAY DIFFRACTION	2.2
6WLX	X-RAY DIFFRACTION	2.2
9I8W	X-RAY DIFFRACTION	2.2
8Z0U	X-RAY DIFFRACTION	2.21
8VME	X-RAY DIFFRACTION	2.3
7UWI	X-RAY DIFFRACTION	2.32
6M92	X-RAY DIFFRACTION	2.35
8Z10	X-RAY DIFFRACTION	2.35
6M91	X-RAY DIFFRACTION	2.4
6O9C	X-RAY DIFFRACTION	2.45
1JPW	X-RAY DIFFRACTION	2.5
1LUJ	X-RAY DIFFRACTION	2.5
1TH1	X-RAY DIFFRACTION	2.5
3SLA	X-RAY DIFFRACTION	2.5
6M93	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35222-F1	81.02	0.63

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 (19): 2, 23, 29, 33, 37, 41, 45, 49, 64, 142, 191, 246, 331, 333, 552, 556, 556, 619, 675

Glycosylation sites (1): 23

Mutagenesis-validated functional residues (22):

Position	Phenotype
29	no effect.
64	abolishes phosphorylation by ptk6.
142	no effect on interaction with bcl9 and bcl9l.
156	abolishes interaction with bcl9 but no effect on interaction with cdh3; when associated with a-159.
159	no effect on interaction with bcl9 and cdh3. abolishes interaction with bcl9 but no effect on interaction with cdh3; whe
178	no effect on interaction with bcl9 and cdh3.
253	abolishes or strongly reduces axin2 binding.
260	abolishes or strongly reduces axin1 and axin2 binding. strongly reduces phosphorylation and degradation; when associated
292	abolishes or strongly reduces axin1 and axin2 binding.
312	abolishes tcf7l2 binding.
333	abolished phosphorylation by src and interaction with isoform m2 of pkm (pkm2).
345	abolishes apc binding.
383	abolishes apc binding. strongly reduces phosphorylation and degradation; when associated with a-260 and a-386.
386	strongly reduces apc binding. strongly reduces phosphorylation and degradation; when associated with a-260 and a-383.
426	abolishes tcf7l2 and lef1 binding.
435	strongly reduces or abolishes lef1 binding.
435	abolishes tcf7l2 binding.
469	abolishes tcf7l2 binding, and strongly reduces or abolishes lef1 binding.
470	abolishes tcf7l2 binding, and strongly reduces or abolishes lef1 binding.
508	abolishes tcf7l2 and lef1 binding.
660	abolishes ctnnbip1 binding; when associated with a-661.
661	abolishes ctnnbip1 binding; when associated with a-660.

Function

Pathways and Gene Ontology

Reactome pathways

46 pathways

ID	Pathway
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3134973	LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
R-HSA-351906	Apoptotic cleavage of cell adhesion proteins
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-381771	Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-4086398	Ca2+ pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-4411364	Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-525793	Myogenesis
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-8876493	InlA-mediated entry of Listeria monocytogenes into host cells
R-HSA-8951430	RUNX3 regulates WNT signaling
R-HSA-9733709	Cardiogenesis
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-9762292	Regulation of CDH11 function
R-HSA-9764302	Regulation of CDH19 Expression and Function
R-HSA-9764561	Regulation of CDH1 Function
R-HSA-9766229	Degradation of CDH1
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 1580 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS

GO Biological Process (212): negative regulation of transcription by RNA polymerase II (GO:0000122), MAPK cascade (GO:0000165), protein polyubiquitination (GO:0000209), embryonic axis specification (GO:0000578), branching involved in blood vessel morphogenesis (GO:0001569), osteoblast differentiation (GO:0001649), branching involved in ureteric bud morphogenesis (GO:0001658), in utero embryonic development (GO:0001701), gastrulation with mouth forming second (GO:0001702), cell fate specification (GO:0001708), endodermal cell fate commitment (GO:0001711), neuron migration (GO:0001764), epithelial to mesenchymal transition (GO:0001837), neural plate development (GO:0001840), positive regulation of neuroblast proliferation (GO:0002052), positive regulation of mesenchymal cell proliferation (GO:0002053), chondrocyte differentiation (GO:0002062), epithelial cell development (GO:0002064), lens morphogenesis in camera-type eye (GO:0002089), outflow tract morphogenesis (GO:0003151), regulation of secondary heart field cardioblast proliferation (GO:0003266), metanephros morphogenesis (GO:0003338), negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis (GO:0003340), transcription by RNA polymerase II (GO:0006366), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), epidermal growth factor receptor signaling pathway (GO:0007173), canonical NF-kappaB signal transduction (GO:0007249), chemical synaptic transmission (GO:0007268), ectoderm development (GO:0007398), glial cell fate determination (GO:0007403), neuroblast proliferation (GO:0007405), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), fibroblast growth factor receptor signaling pathway (GO:0008543), response to xenobiotic stimulus (GO:0009410), anterior/posterior axis specification (GO:0009948), dorsal/ventral axis specification (GO:0009950), proximal/distal pattern formation (GO:0009954), positive regulation of gene expression (GO:0010628)

GO Molecular Function (23): transcription coregulator binding (GO:0001221), transcription corepressor binding (GO:0001222), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), signaling receptor binding (GO:0005102), nuclear receptor binding (GO:0016922), enzyme binding (GO:0019899), kinase binding (GO:0019900), protein kinase binding (GO:0019901), phosphatase binding (GO:0019902), protein phosphatase binding (GO:0019903), nuclear estrogen receptor binding (GO:0030331), ubiquitin protein ligase binding (GO:0031625), transmembrane transporter binding (GO:0044325), alpha-catenin binding (GO:0045294), cadherin binding (GO:0045296), SMAD binding (GO:0046332), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), I-SMAD binding (GO:0070411), disordered domain specific binding (GO:0097718), DNA-binding transcription factor binding (GO:0140297), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515)

GO Cellular Component (54): euchromatin (GO:0000791), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), fascia adherens (GO:0005916), bicellular tight junction (GO:0005923), focal adhesion (GO:0005925), cilium (GO:0005929), cell cortex (GO:0005938), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apicolateral plasma membrane (GO:0016327), lateral plasma membrane (GO:0016328), catenin complex (GO:0016342), flotillin complex (GO:0016600), Z disc (GO:0030018), lamellipodium (GO:0030027), cell junction (GO:0030054), beta-catenin destruction complex (GO:0030877), microvillus membrane (GO:0031528), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993), Scrib-APC-beta-catenin complex (GO:0034750), ciliary basal body (GO:0036064), presynaptic membrane (GO:0042734), apical part of cell (GO:0045177), synapse (GO:0045202), postsynaptic membrane (GO:0045211), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), beta-catenin-TCF7L2 complex (GO:0070369), cell periphery (GO:0071944), Schaffer collateral - CA1 synapse (GO:0098685)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
TCF dependent signaling in response to WNT	3
Signaling by WNT	2
Degradation of beta-catenin by the destruction complex	1
Cytosolic sensors of pathogen-associated DNA	1
Apoptotic cleavage of cellular proteins	1
Incretin synthesis, secretion, and inactivation	1
Beta-catenin independent WNT signaling	1
Cell-cell junction organization	1
Formation of the beta-catenin:TCF transactivating complex	1
VEGFA-VEGFR2 Pathway	1
Developmental Biology	1
Signaling by WNT in cancer	1
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	5
branching morphogenesis of an epithelial tube	2
cell differentiation	2
chordate embryonic development	2
anatomical structure morphogenesis	2
enzyme binding	2
cytoplasm	2
cell periphery	2
cell-cell junction	2
plasma membrane region	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
intracellular signaling cassette	1
protein ubiquitination	1
axis specification	1
embryonic pattern specification	1
angiogenesis	1
blood vessel morphogenesis	1
ossification	1
ureteric bud morphogenesis	1
gastrulation	1
cell fate commitment	1
cellular developmental process	1
endodermal cell differentiation	1
cell fate commitment involved in formation of primary germ layer	1
cell migration	1
generation of neurons	1
mesenchymal cell differentiation	1
epithelium development	1
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
cartilage development	1
epithelial cell differentiation	1

Protein interactions and networks

STRING

12457 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTNNB1	CDH17	Q12864	999
CTNNB1	CDH1	P12830	999
CTNNB1	AXIN1	O15169	999
CTNNB1	LEF1	Q9UJU2	999
CTNNB1	CDH2	P19022	999
CTNNB1	HNF4A	P41235	999
CTNNB1	GSK3B	P49841	999
CTNNB1	TCF7L2	Q9NQB0	998
CTNNB1	CTNNA1	P35221	997
CTNNB1	TCF7	P36402	997
CTNNB1	BTRC	Q9Y297	997
CTNNB1	CTNND1	O60716	997
CTNNB1	BCL9	O00512	996
CTNNB1	APC	P25054	996
CTNNB1	CDH5	P33151	995

IntAct

1013 interactions, top by confidence:

A	B	Type	Score
TCF7L2	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.970
CTNNB1	TCF7L2	psi-mi:“MI:0915”(physical association)	0.970
TCF7L2	CTNNB1	psi-mi:“MI:0915”(physical association)	0.970
CTNNBIP1	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.960
APC	CTNNB1	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	APC	psi-mi:“MI:0407”(direct interaction)	0.960
CDH1	CTNNB1	psi-mi:“MI:0914”(association)	0.960
CTNNB1	CDH1	psi-mi:“MI:0914”(association)	0.960
CTNNB1	CDH1	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	APC	psi-mi:“MI:0915”(physical association)	0.960
GSK3B	CTNNB1	psi-mi:“MI:0915”(physical association)	0.950
AXIN1	CTNNB1	psi-mi:“MI:0914”(association)	0.940
CTNNB1	TCF4	psi-mi:“MI:0915”(physical association)	0.940
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
TCF4	CTNNB1	psi-mi:“MI:0914”(association)	0.940
CTNNB1	BTRC	psi-mi:“MI:0915”(physical association)	0.930
CDH2	CTNNB1	psi-mi:“MI:0915”(physical association)	0.930
CDH2	CTNNB1	psi-mi:“MI:0914”(association)	0.930
CTNNB1	CDH2	psi-mi:“MI:0915”(physical association)	0.930
AR	CTNNB1	psi-mi:“MI:0915”(physical association)	0.890

BioGRID (2198): CTNNB1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-MS), CTNNB1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-MS), CTNNB1 (Affinity Capture-Western), RNF220 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-MS), TCF4 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), SOX1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-RNA), CTNNB1 (Affinity Capture-RNA)

ESM2 similar proteins: B1H1Z8, B4ZIX8, B6V8E6, F1LSG8, O43913, O94826, P35222, P42232, P51692, P52632, P97834, Q02248, Q0VCJ8, Q0VCX4, Q13042, Q13098, Q3MHJ2, Q3T0V3, Q4R5H6, Q5F415, Q5RF08, Q5ZIL9, Q5ZMH6, Q6GR10, Q6NRT5, Q7SXR3, Q8BPU7, Q8CI71, Q8MJJ1, Q8R349, Q8R3S6, Q8VC42, Q91YQ7, Q92556, Q95115, Q96DM3, Q96G75, Q96JG6, Q99LD4, Q9CQC8

Diamond homologs: B6V8E6, F1QGH7, P14923, P18824, P26233, P30998, P35222, P35223, P35224, Q02248, Q02257, Q02453, Q0VCX4, Q17GS9, Q29I35, Q6P0K8, Q7QHW5, Q8SPJ1, Q8WNW3, Q9PVF7, Q9WU82, O44326, Q10953

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
CBY1	down-regulates	CTNNB1	binding
RXRA	down-regulates	CTNNB1	binding
SRC	“up-regulates activity”	CTNNB1	phosphorylation
SRC	“down-regulates activity”	CTNNB1	phosphorylation
AR	“down-regulates quantity by repression”	CTNNB1	“transcriptional regulation”
AXIN2	down-regulates	CTNNB1
GSK3B	“down-regulates activity”	CTNNB1	phosphorylation
BCL9	up-regulates	CTNNB1	binding
CHD8	down-regulates	CTNNB1	binding
SMAD7	up-regulates	CTNNB1
CTNNB1	“up-regulates quantity by expression”	CCND1	“transcriptional regulation”
CTNNB1	“up-regulates activity”	LEF1	binding
CTNNB1	up-regulates	TCF7	binding
DVL1	“up-regulates activity”	CTNNB1	binding
PRKACA	“up-regulates activity”	CTNNB1	phosphorylation
AKT2	“up-regulates activity”	CTNNB1
CTNNB1	up-regulates	TRRAP	binding
CDC73	up-regulates	CTNNB1	binding
AKT2	up-regulates	CTNNB1	phosphorylation
BCR-ABL	up-regulates	CTNNB1	phosphorylation
BCR-ABL	down-regulates	CTNNB1	phosphorylation
MAML1	up-regulates	CTNNB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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
Signaling by WNT in cancer	6	49.4×	2e-07
Repression of WNT target genes	5	48.9×	3e-06
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	5	34.0×	2e-05
Disassembly of the destruction complex and recruitment of AXIN to the membrane	6	29.3×	3e-06
Deactivation of the beta-catenin transactivating complex	9	28.7×	3e-09
Degradation of beta-catenin by the destruction complex	11	26.1×	7e-11
Signaling by WNT	16	24.5×	1e-15
TCF dependent signaling in response to WNT	15	24.2×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of extrinsic apoptotic signaling pathway	6	30.1×	9e-06
canonical Wnt signaling pathway	14	25.5×	3e-13
positive regulation of protein localization to nucleus	5	23.3×	2e-04
positive regulation of cell differentiation	6	19.1×	1e-04
positive regulation of epithelial to mesenchymal transition	5	18.9×	5e-04
negative regulation of canonical Wnt signaling pathway	12	16.8×	4e-09
cell morphogenesis	8	15.0×	1e-05
positive regulation of protein ubiquitination	5	12.7×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 20 cancer types — ACC, COAD, COADREAD, ESCA, HCC, LIHB, LUAD, MBL, MEL, NSCLC, OVT, PAST…(+8 more).

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	172
Likely pathogenic	56
Uncertain significance	316
Likely benign	290
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013467	NM_001904.4(CTNNB1):c.788del (p.Leu263fs)	Pathogenic
1029546	NM_001904.4(CTNNB1):c.1829_1832del (p.Ile610fs)	Pathogenic
1072445	NM_001904.4(CTNNB1):c.67dup (p.Ser23fs)	Pathogenic
1074288	NM_001904.4(CTNNB1):c.1142_1143del (p.Cys381fs)	Pathogenic
1075754	NM_001904.4(CTNNB1):c.2139del (p.Pro714fs)	Pathogenic
1164027	NM_001904.4(CTNNB1):c.646G>A (p.Gly216Arg)	Pathogenic
1174512	NM_001904.4(CTNNB1):c.1706del (p.Ile569fs)	Pathogenic
1193715	NM_001904.4(CTNNB1):c.1923dup (p.Glu642fs)	Pathogenic
1196551	NM_001904.4(CTNNB1):c.367C>T (p.Gln123Ter)	Pathogenic
1208312	NM_001904.4(CTNNB1):c.1081+1G>T	Pathogenic
1315504	NM_001904.4(CTNNB1):c.1924G>T (p.Glu642Ter)	Pathogenic
1319219	NM_001904.4(CTNNB1):c.417_420del (p.Ile140fs)	Pathogenic
1320077	NM_001904.4(CTNNB1):c.163G>T (p.Glu55Ter)	Pathogenic
1320120	NM_001904.4(CTNNB1):c.1082-1G>C	Pathogenic
1320247	NM_001904.4(CTNNB1):c.2008dup (p.Tyr670fs)	Pathogenic
1329943	NM_001904.4(CTNNB1):c.564dup (p.Met189fs)	Pathogenic
133315	NM_001904.4(CTNNB1):c.705dup (p.Gly236fs)	Pathogenic
1343152	NM_001904.4(CTNNB1):c.133del (p.Ser45fs)	Pathogenic
1344804	NM_001904.4(CTNNB1):c.160G>T (p.Glu54Ter)	Pathogenic
1361777	NM_001904.4(CTNNB1):c.366_367insT (p.Gln123fs)	Pathogenic
1375966	NM_001904.4(CTNNB1):c.2141del (p.Pro714fs)	Pathogenic
1385459	NM_001904.4(CTNNB1):c.1510dup (p.Trp504fs)	Pathogenic
1388940	NC_000003.12:g.41233529del	Pathogenic
1394276	NM_001904.4(CTNNB1):c.1528del (p.Thr510fs)	Pathogenic
1394975	NM_001904.4(CTNNB1):c.1475dup (p.Val493fs)	Pathogenic
1399229	NM_001904.4(CTNNB1):c.181C>T (p.Gln61Ter)	Pathogenic
1404757	NM_001904.4(CTNNB1):c.1283_1298del (p.Thr428fs)	Pathogenic
1413665	NM_001904.4(CTNNB1):c.1272_1273del (p.Leu424_Ser425insTer)	Pathogenic
1453663	NM_001904.4(CTNNB1):c.1033A>T (p.Lys345Ter)	Pathogenic
1453745	NM_001904.4(CTNNB1):c.696del (p.Phe232fs)	Pathogenic

SpliceAI

2594 predictions. Top by Δscore:

Variant	Effect	Δscore
3:41195707:G:GG	donor_gain	1.0000
3:41224019:AG:A	acceptor_gain	1.0000
3:41224020:GG:G	acceptor_gain	1.0000
3:41224020:GGGT:G	acceptor_gain	1.0000
3:41224522:ATAG:A	acceptor_loss	1.0000
3:41224523:T:G	acceptor_gain	1.0000
3:41224523:TA:T	acceptor_loss	1.0000
3:41224524:A:AG	acceptor_gain	1.0000
3:41224524:A:C	acceptor_loss	1.0000
3:41224524:AGCT:A	acceptor_gain	1.0000
3:41224525:G:GA	acceptor_gain	1.0000
3:41224525:GC:G	acceptor_gain	1.0000
3:41224525:GCT:G	acceptor_gain	1.0000
3:41224525:GCTG:G	acceptor_gain	1.0000
3:41224525:GCTGA:G	acceptor_gain	1.0000
3:41224750:GCTG:G	donor_gain	1.0000
3:41224751:CTGG:C	donor_loss	1.0000
3:41224752:TGG:T	donor_loss	1.0000
3:41224754:G:GG	donor_gain	1.0000
3:41224754:GT:G	donor_loss	1.0000
3:41224755:T:G	donor_loss	1.0000
3:41224950:CCAG:C	acceptor_loss	1.0000
3:41224951:CAG:C	acceptor_loss	1.0000
3:41224952:A:AG	acceptor_gain	1.0000
3:41224953:G:GG	acceptor_gain	1.0000
3:41224953:GAT:G	acceptor_gain	1.0000
3:41225205:CAGGT:C	donor_loss	1.0000
3:41225207:GGT:G	donor_loss	1.0000
3:41225208:G:GG	donor_gain	1.0000
3:41225209:T:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012468 (3:41201460 C>T), RS1000088680 (3:41207468 C>G,T), RS1000102695 (3:41235341 A>G), RS1000147234 (3:41238685 G>A), RS1000250218 (3:41213107 C>T), RS1000285710 (3:41226258 A>C,G), RS1000524945 (3:41208030 A>G), RS1000623860 (3:41203134 A>G), RS1000703442 (3:41233670 G>T), RS1000740034 (3:41240628 G>A), RS1000744720 (3:41218277 A>C,T), RS1000766333 (3:41231786 T>G), RS1000800148 (3:41217883 A>G), RS1000877506 (3:41226980 C>A,G,T), RS1000929562 (3:41226802 A>C)

Disease associations

OMIM: gene MIM:116806 | disease phenotypes: MIM:617572, MIM:615075, MIM:114500, MIM:174050, MIM:114550, MIM:132600, MIM:155255, MIM:135290, MIM:167000, MIM:133780, MIM:109800, MIM:207500, MIM:301800

GenCC curated gene-disease

Disease	Classification	Inheritance
severe intellectual disability-progressive spastic diplegia syndrome	Definitive	Autosomal dominant
exudative vitreoretinopathy	Definitive	Autosomal dominant
exudative vitreoretinopathy 7	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy	Definitive	AD

Mondo (29): exudative vitreoretinopathy 7 (MONDO:0033123), severe intellectual disability-progressive spastic diplegia syndrome (MONDO:0014035), colorectal cancer (MONDO:0005575), congenital nervous system disorder (MONDO:0002320), autosomal dominant polycystic liver disease (MONDO:0000447), hepatocellular carcinoma (MONDO:0007256), pilomatrixoma (MONDO:0007564), medulloblastoma (MONDO:0007959), ovarian neoplasm (MONDO:0021068), neurodevelopmental disorder (MONDO:0700092), colon carcinoma (MONDO:0002032), Wilms tumor (MONDO:0006058), atypical endometrial hyperplasia (MONDO:0006096), desmoid tumor (MONDO:0007608), ovarian cancer (MONDO:0008170)

Orphanet (17): Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome (Orphanet:404473), Isolated polycystic liver disease (Orphanet:2924), Medulloblastoma (Orphanet:616), Hepatocellular carcinoma (Orphanet:88673), Pilomatrixoma (Orphanet:91414), Nephroblastoma (Orphanet:654), Rare ovarian cancer (Orphanet:213500), Hepatoblastoma (Orphanet:449), Desmoid tumor (Orphanet:873), Familial prostate cancer (Orphanet:1331), Familial exudative vitreoretinopathy (Orphanet:891), Retinopathy of prematurity (Orphanet:90050), Juvenile nasopharyngeal angiofibroma (Orphanet:289596), Non-syndromic anorectal malformation (Orphanet:557), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

256 total (30 of 256 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000080	Abnormality of reproductive system physiology
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000190	Abnormal oral frenulum morphology
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000270	Delayed cranial suture closure
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000495_4	Bone mineral density (hip)	8.000000e-10
GCST003017_1	Colorectal cancer	2.000000e-08
GCST003017_7	Colorectal cancer	3.000000e-09
GCST003559_1	Bone mineral density (hip)	9.000000e-09
GCST005795_17	Femoral neck bone mineral density	1.000000e-16
GCST005796_6	Lumbar spine bone mineral density	3.000000e-12
GCST006143_2	Bone mineral density (total hip)	4.000000e-07
GCST006288_247	Heel bone mineral density	4.000000e-26
GCST006288_305	Heel bone mineral density	2.000000e-17
GCST006288_512	Heel bone mineral density	1.000000e-40
GCST006423_2	Fracture	5.000000e-12
GCST006624_52	Systolic blood pressure	4.000000e-13
GCST006979_61	Heel bone mineral density	1.000000e-21
GCST006979_62	Heel bone mineral density	7.000000e-148
GCST007691_11	Femoral neck bone mineral density	4.000000e-25
GCST007856_76	Colorectal cancer or advanced adenoma	1.000000e-16
GCST009962_2	High myopia	4.000000e-08
GCST010002_421	Refractive error	3.000000e-27

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D001006	Anus, Imperforate	C06.198.050; C16.131.314.094
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D018222	Desmoid Tumors	C04.557.450.565.590.340.410
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D018197	Hepatoblastoma	C04.557.435.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D010026	Osteosclerosis	C05.116.099.708.702
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D018296	Pilomatrixoma	C04.557.470.565.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D013724	Teratoma	C04.557.465.910
D009396	Wilms Tumor	C04.557.435.595; C04.588.945.947.535.585; C04.700.900; C12.050.351.937.820.535.585; C12.050.351.968.419.473.585; C12.200.758.820.750.585; C12.200.777.419.473.585; C12.900.820.535.585; C12.950.419.473.585; C12.950.983.535.585; C16.320.700.900
C536382	Exudative vitreoretinopathy 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL3038464 (PROTEIN COMPLEX), CHEMBL3038511 (PROTEIN COMPLEX), CHEMBL3885520 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885525 (PROTEIN COMPLEX), CHEMBL3885541 (PROTEIN COMPLEX), CHEMBL3885542 (PROTEIN-PROTEIN INTERACTION), CHEMBL4665593 (PROTEIN-PROTEIN INTERACTION), CHEMBL4888449 (PROTEIN-PROTEIN INTERACTION), CHEMBL5291978 (PROTEIN COMPLEX), CHEMBL5866 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 84,562 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL421701	DITHIAZANINE IODIDE	4	3,372
CHEMBL50	QUERCETIN	3	74,559
CHEMBL1208572	SALINOMYCIN	2	6,527
CHEMBL4650339	DALOSIRVAT	2	104

Clinical evidence (CIViC)

Drug × variant × indication: 6 predictive associations from 6 curated evidence items; also 18 diagnostic, 7 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
CTNNB1 S45F	Imatinib	Desmoid Tumor	Sensitivity/Response	CIViC B	EID11018
CTNNB1 T41A	Meloxicam	Desmoid Tumor	Sensitivity/Response	CIViC B	EID6050
CTNNB1 T41A		Hepatoblastoma	Sensitivity/Response	CIViC B	EID6078
CTNNB1 S45F	Meloxicam	Desmoid Tumor	Sensitivity/Response	CIViC C	EID6049
CTNNB1 T41A	Celecoxib	Desmoid Tumor	Sensitivity/Response	CIViC C	EID6048
CTNNB1 Activating Mutation	Anti-CTLA-4 Monoclonal Antibody + Anti-PD-L1 Monoclonal Antibody	Melanoma	Resistance	CIViC D	EID2988

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4135385	Efficacy,Toxicity	3	cyclophosphamide;dexamethasone;lenalidomide;thalidomide	Multiple Myeloma
rs4533622	Efficacy,Toxicity	3	lenalidomide;thalidomide	Multiple Myeloma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4135385	CTNNB1	3	4.00	1	cyclophosphamide;dexamethasone;lenalidomide;thalidomide
rs4533622	CTNNB1	3	3.50	1	lenalidomide;thalidomide

Binding affinities (BindingDB)

63 measured of 77 human assays (77 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-pyridin-2-ylbutane-1,4-dione	IC50	13 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-phenylbutane-1,4-dione	IC50	28.5 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-thiophen-2-ylbutane-1,4-dione	IC50	38.5 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(2-hydroxyphenyl)butane-1,4-dione	IC50	83 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(4-fluorophenyl)butane-1,4-dione	IC50	183 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
4-[2-[[2-(hydroxymethyl)-3H-benzimidazol-5-yl]amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-(3H-benzimidazol-5-ylamino)-7-methylquinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[7-bromo-2-[(2-methyl-3H-benzimidazol-5-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[(2,7-dimethyl-3H-benzimidazol-5-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[[2-(methoxymethyl)-3H-benzimidazol-5-yl]amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[[2-[(1S)-1-hydroxyethyl]-3H-benzimidazol-5-yl]amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[(6-methyl-1H-benzimidazol-5-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-(3H-benzimidazol-5-ylamino)-6-fluoroquinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-(quinolin-6-ylamino)quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[(2-methylquinolin-6-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-(isoquinolin-6-ylamino)quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-(isoquinolin-5-ylamino)quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[(7-fluoroquinolin-4-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
4-[2-[(7-methoxyquinolin-4-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	650 nM	US-9682961: Quinazoline derivative
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-[4-(2-methoxyethoxymethoxy)phenyl]butane-1,4-dione	IC50	805 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-pyridin-2-yl-4-thiophen-2-ylbutane-1,4-dione	IC50	1270 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-pyridin-2-ylpropane-1,3-dione	IC50	1390 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
4-[2-[(7-bromo-2-methyl-3H-benzimidazol-5-yl)amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	2000 nM	US-9682961: Quinazoline derivative
4-[2-[[2-(trifluoromethyl)-3H-benzimidazol-5-yl]amino]quinazolin-8-yl]oxycyclohexan-1-ol	IC50	2000 nM	US-9682961: Quinazoline derivative
4-[2-(isoquinolin-7-ylamino)quinazolin-8-yl]oxycyclohexan-1-ol	IC50	2000 nM	US-9682961: Quinazoline derivative
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(3-hydroxyphenyl)butane-1,4-dione	IC50	2100 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-thiophen-2-ylpropane-1,3-dione	IC50	2570 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-hydroxy-N-(2H-tetrazol-5-ylmethyl)indazol-5-amine	KI	3380 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
1-hydroxy-N-(2H-tetrazol-5-ylmethyl)benzotriazol-5-amine	KI	3380 nM	US-9738628: Substituted 1H-indazol-1-OL analogs as inhibitors of beta catenin/Tcf protein-protein interactions
2-(naphthalen-1-ylmethyl)-1,3-diphenylpropane-1,3-dione	IC50	3900 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2,2-diethyl-3-phenylpropane-1,3-dione	IC50	6000 nM	US-10314832: β- and γ-diketones and γ-hydroxyketones as Wnt/β-catenin signaling pathway activators
4-(3-((S)-3-Ethyl-4-(4’-fluoro-6- (((S)-pyrrolidin-1-ium-3-yl)oxy)- [1,1’-biphenyl]-3-carbonyl) piperazine-1-carbonyl)-5- fluorophenyl)piperazin-1-ium chloride	KI	10000 nM	US-11634409: Compounds for the treatment of BRAF-associated diseases and disorders
1-hydroxy-5-(2H-tetrazol-5-ylmethoxymethyl)benzotriazole	KI	13600 nM	US-9738628: Substituted 1H-indazol-1-OL analogs as inhibitors of beta catenin/Tcf protein-protein interactions
1-hydroxy-5-(tetrazol-1-ylmethoxymethyl)indazole	KI	13600 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
(S)-1-(3-Fluoro-5-(4-(4-(pyrrolidin- 3-yloxy)-3-(4-(trifluoromethyl) cyclohexyl)benzoyl)piperazine-1- carbonyl)phenyl)piperazin-2-one hydrochloride	KI	14000 nM	US-11634409: Compounds for the treatment of BRAF-associated diseases and disorders
N-(1-hydroxyindazol-5-yl)-3,5-dimethyl-N-(tetrazolidin-5-ylmethyl)-1,2-oxazole-4-carboxamide	KI	16600 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
4-(3-Fluoro-5-((5)-4-(4’-fluoro-6- (((S)-pyrrolidin-1-ium-3-yl)oxy)- [1,1’-biphenyl]-3-carbonyl)-3- isobutylpiperazine-1-carbonyl) phenyl)piperazin-1-ium chloride	KI	22000 nM	US-11634409: Compounds for the treatment of BRAF-associated diseases and disorders
3-[2-(1-hydroxybenzotriazol-5-yl)ethyl]-1,2,4-oxadiazolidine-5-thione	KI	24400 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
3-bromo-5-fluoro-N-(1-hydroxyindazol-5-yl)-N-(tetrazolidin-5-ylmethyl)benzamide	KI	28700 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
3-chloro-N-(1-hydroxyindazol-5-yl)-N-(tetrazolidin-5-ylmethyl)benzamide	KI	33100 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
(S)-1-(3-(4-(3-Cyclohexyl-4- (pyrrolidin-3-yloxy)benzoyl) piperazine-1-carbonyl)-5- fluorophenyl)piperazin-2-one hydrochloride	KI	39000 nM	US-11634409: Compounds for the treatment of BRAF-associated diseases and disorders
(5Z)-5-[(2,5-dimethyl-1-pyridin-3-ylpyrrol-3-yl)methylidene]-3-phenyl-1,3-thiazolidine-2,4-dione	KI	40700 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
4-(3-Fluoro-5-((5)-4-(4’-fluoro-6- (((S)-pyrrolidin-1-ium-3-yl)oxy)- [1,1’-biphenyl]-3-carbonyl)-3- isopropylpiperazine-1-carbonyl) phenyl)piperazin-1-ium chloride	KI	45000 nM	US-11634409: Compounds for the treatment of BRAF-associated diseases and disorders
4-[(5Z)-5-[(3,4-dimethoxyphenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoic acid	KI	46800 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
1-hydroxy-5-(2H-tetrazol-5-ylmethoxy)benzotriazole	KI	50400 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
[(2R)-1-[3,10-dihydroxy-12-[(2R)-2-(4-hydroxyphenoxy)carbonyloxypropyl]-2,6,7,11-tetramethoxy-4,9-dioxoperylen-1-yl]propan-2-yl] benzoate	KI	53800 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
1-hydroxy-5-[2-(tetrazol-1-yl)ethyl]benzotriazole	KI	54200 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
CHEBI:3556	KI	62500 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
3-[2-(1-hydroxyindazol-5-yl)ethyl]-1,2,4-oxadiazolidine-5-thione	KI	70400 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
3-[2-(1-hydroxyindazol-5-yl)ethyl]-1,2,4-oxadiazolidin-5-one	KI	97700 nM	US-9284299: Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions

ChEMBL bioactivities

1160 potent at pChembl≥5 of 1553 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	EC50	1	nM	CHEMBL6055833
8.71	EC50	1.96	nM	CHEMBL5947546
8.70	EC50	2	nM	CHEMBL5913745
8.70	EC50	2	nM	CHEMBL5981469
8.67	EC50	2.16	nM	CHEMBL5859963
8.60	EC50	2.5	nM	CHEMBL6007715
8.52	EC50	3	nM	CHEMBL6011770
8.52	EC50	3	nM	CHEMBL5947221
8.40	EC50	4	nM	CHEMBL5901304
8.38	IC50	4.2	nM	CHEMBL5282944
8.30	Kd	5	nM	CHEMBL5205469
8.30	Kd	5	nM	CHEMBL5180356
8.30	EC50	5	nM	CHEMBL6013490
8.30	EC50	5	nM	CHEMBL5767277
8.22	EC50	6	nM	CHEMBL5847625
8.15	EC50	7	nM	CHEMBL6062887
8.10	EC50	8	nM	CHEMBL5777177
8.05	EC50	9	nM	CHEMBL6007738
8.05	EC50	9	nM	CHEMBL6014713
8.05	EC50	9	nM	CHEMBL5836456
8.05	EC50	9	nM	CHEMBL6031869
8.00	EC50	10	nM	CHEMBL5809256
8.00	EC50	10	nM	CHEMBL5810383
8.00	EC50	10	nM	CHEMBL5950600
7.96	EC50	11	nM	CHEMBL6052087
7.92	EC50	12	nM	CHEMBL5814663
7.89	Kd	13	nM	CHEMBL2397076
7.89	Kd	13	nM	CHEMBL5194459
7.89	Kd	13	nM	CHEMBL5275939
7.89	IC50	13	nM	CHEMBL6027496
7.89	EC50	13	nM	CHEMBL5762849
7.89	EC50	13	nM	CHEMBL5896792
7.89	EC50	13	nM	CHEMBL6032861
7.85	EC50	14	nM	CHEMBL5977287
7.80	IC50	16	nM	CHEMBL5285550
7.80	EC50	16	nM	CHEMBL5759600
7.80	EC50	16	nM	CHEMBL6054961
7.80	EC50	16	nM	CHEMBL5887779
7.77	EC50	17	nM	CHEMBL5846932
7.75	EC50	18	nM	CHEMBL5744572
7.75	EC50	18	nM	CHEMBL5847808
7.75	EC50	18	nM	CHEMBL5835155
7.66	EC50	22	nM	CHEMBL5872532
7.62	EC50	24	nM	CHEMBL5932589
7.60	EC50	25	nM	CHEMBL6031639
7.58	EC50	26	nM	CHEMBL6054653
7.58	EC50	26	nM	CHEMBL5798829
7.54	IC50	28.5	nM	DALOSIRVAT
7.51	EC50	31	nM	CHEMBL6052011
7.50	EC50	32	nM	CHEMBL5810480

PubChem BioAssay actives

498 with measured affinity, of 1193 total; 50 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
(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(3-amino-3-oxopropyl)-2-[(2S)-butan-2-yl]-8-[3-(diaminomethylideneamino)propyl]-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-4-methylpentanoyl]-naphthalen-2-ylamino]propanoic acid	1924303: Binding affinity to human beta catenin assessed as dissociation constant	ic50	0.0042	uM
(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(3R,6S,9S,12S,15R,19Z)-15-[[(2S)-2-[[(2S)-1-[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]-12-[(2S)-butan-2-yl]-6-(carboxymethyl)-9-(2-methylpropyl)-5,8,11,14-tetraoxo-1,17-dithia-4,7,10,13-tetrazacyclohenicos-19-ene-3-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoic acid	1851003: Binding affinity to human beta-catenin (129 to 780 residues) expressed in Escherichia coli Rosetta blue assessed as dissociation constant using fluorescent peptide as substrate incubated for 20 mins by fluorescence polarisation assay	kd	0.0050	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(3R,6S,9S,12S,15R,19Z)-3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-12-[(2S)-butan-2-yl]-6-(carboxymethyl)-9-(2-methylpropyl)-5,8,11,14-tetraoxo-1,17-dithia-4,7,10,13-tetrazacyclohenicos-19-en-15-yl]amino]-5-oxopentanoic acid	1851003: Binding affinity to human beta-catenin (129 to 780 residues) expressed in Escherichia coli Rosetta blue assessed as dissociation constant using fluorescent peptide as substrate incubated for 20 mins by fluorescence polarisation assay	kd	0.0050	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-5-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-2-[(2S)-butan-2-yl]-8-(carboxymethyl)-11,20-dimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoic acid	1851001: Binding affinity to human beta-catenin (134 to 665 residues) expressed in Escherichia coli BL21 assessed as dissociation constant incubated for 45 mins by fluorescence polarisation assay	kd	0.0130	uM
2-[(3S,6S,9R,12R,16E,21R)-12-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-amino-5-oxopentanoyl]amino]-21-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-9-[(2S)-butan-2-yl]-6-tert-butyl-12,21-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-3-yl]acetic acid	1924295: Binding affinity to human full length beta catenin expressed in Escherichia coli (BL21) DE3 assessed as dissociation constant by fluorescence based analysis	kd	0.0130	uM
2-[(3S,6S,9S,12S,16Z,21S)-12-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-amino-5-oxopentanoyl]amino]-21-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-9-[(2S)-butan-2-yl]-12,21-dimethyl-6-(2-methylpropyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-3-yl]acetic acid	754520: Binding affinity to human beta-catenin expressed in Escherichia coli BL21 after 45 mins by fluorescence polarization assay	kd	0.0130	uM
6-[4-[2-(diethylamino)ethoxy]phenyl]-3,8-dimethylpteridine-2,4-dione	1958858: Inhibition of beta catenin/Tcf4 (unknown origin) protein protein interaction	ic50	0.0160	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-2-[(2S)-butan-2-yl]-8-(carboxymethyl)-11,20-dimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoic acid	1851001: Binding affinity to human beta-catenin (134 to 665 residues) expressed in Escherichia coli BL21 assessed as dissociation constant incubated for 45 mins by fluorescence polarisation assay	kd	0.0530	uM
2-[(3S,6S,9R,12R,16E,21R)-12-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-21-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-9-[(2S)-butan-2-yl]-6-tert-butyl-12,21-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-3-yl]acetic acid	1924295: Binding affinity to human full length beta catenin expressed in Escherichia coli (BL21) DE3 assessed as dissociation constant by fluorescence based analysis	kd	0.0530	uM
2-[(3S,6S,9S,12S,16Z,21S)-12-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-21-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-9-[(2S)-butan-2-yl]-12,21-dimethyl-6-(2-methylpropyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-3-yl]acetic acid	754520: Binding affinity to human beta-catenin expressed in Escherichia coli BL21 after 45 mins by fluorescence polarization assay	kd	0.0530	uM
(4S)-5-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-5-amino-1-[[(3S,6S,9R,12R,16E,21R)-21-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-9-[(2S)-butan-2-yl]-6-tert-butyl-3-(carboxymethyl)-12,21-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-4-[3-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]propanoylamino]-5-oxopentanoic acid	1924294: Binding affinity to beta catenin (unknown origin) assessed as dissociation constant by VP-ITC method	kd	0.0600	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]-2-[(2S)-butan-2-yl]-8-(carboxymethyl)-11,20-dimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoic acid	754520: Binding affinity to human beta-catenin expressed in Escherichia coli BL21 after 45 mins by fluorescence polarization assay	kd	0.0600	uM
1-cyclopropyl-3-[(3R)-1-[3-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)oxyphenyl]piperidin-3-yl]-1-[[4-(1H-pyrazol-4-yl)phenyl]methyl]urea	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.0740	uM
1-cyclopropyl-3-[(3R)-1-[3-(2-methyl-1-morpholin-4-yl-1-oxopropan-2-yl)oxyphenyl]piperidin-3-yl]-1-[[4-(1H-pyrazol-4-yl)phenyl]methyl]urea	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.0790	uM
N-[2-[2-(2-aminoethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.0820	uM
2-[(1R,4S,7S,10S,13S,19S,25S,28S,31S,34S,37S,40R,43S,54S,59E)-7-(2-amino-2-oxoethyl)-43-benzyl-10-(carboxymethyl)-4-[3-(diaminomethylideneamino)propyl]-31-(hydroxymethyl)-34,37-bis(2-methylpropyl)-2,5,8,11,14,20,26,29,32,35,38,41,44,48,52,55-hexadecaoxo-13,54-di(propan-2-yl)-58,63-dithia-3,6,9,12,15,21,27,30,33,36,39,42,45,49,53,56-hexadecazatetracyclo[38.16.8.015,19.021,25]tetrahexacont-59-en-28-yl]acetic acid	1851012: Binding affinity to full-length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant incubated for 1 hr by fluorescence polarisation assay	kd	0.0910	uM
3-(3,4-difluorophenyl)-N-[4-(4-fluorophenyl)-3-[(3S)-pyrrolidin-3-yl]oxyphenyl]-4-[(3S)-pyrrolidin-3-yl]oxybenzamide	1924309: Binding affinity to human beta catenin double mutant assessed as dissociation constant by alpha assay	kd	0.0970	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[5-(1H-pyrazol-4-yl)-2-pyridinyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1000	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1100	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15Z,20S)-2-[(2S)-butan-2-yl]-20-[[(2S)-6-carbamimidamido-2-[[(2S)-1-[(2S)-2-[[(2S)-6-carbamimidamido-2-[[(2S)-6-carbamimidamido-2-[[(2S)-2-[[(2S)-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-8-(carboxymethyl)-11,20-dimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-6-carbamimidamidohexanoyl]amino]-6-carbamimidamidohexanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-carbamimidamidohexanoic acid	1851002: Binding affinity to full-length recombinant beta-catenin (unknown origin) assessed as dissociation constant by fluorescence polarisation assay	kd	0.1230	uM
N-(3-aminopropyl)-2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1300	uM
N-(3-aminopropyl)-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1300	uM
2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1400	uM
2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-(2-hydroxyethyl)-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1500	uM
2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(3S)-3-hydroxypyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1500	uM
methyl 2-[[2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanoyl]amino]acetate	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1500	uM
[4-[[(6S,9S,9aS)-1-(benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate	1923824: Antagonist activity at CBP/beta-catenin (unknown origin) protein-protein interaction	ic50	0.1500	uM
2-[(3S,9S,12S,15S,18S,21S,24S,35S,38S,41S,44S,47S,50S,53S)-15-(2-amino-2-oxoethyl)-35-benzyl-12-(carboxymethyl)-18-[3-(diaminomethylideneamino)propyl]-21-[(1R)-1-hydroxyethyl]-47-(hydroxymethyl)-41,44-bis(2-methylpropyl)-2,8,11,14,17,20,23,26,30,34,37,40,43,46,49,52-hexadecaoxo-9,24,38-tri(propan-2-yl)-1,7,10,13,16,19,22,25,29,33,36,39,42,45,48,51-hexadecazatricyclo[51.3.0.03,7]hexapentacontan-50-yl]acetic acid	1851012: Binding affinity to full-length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant incubated for 1 hr by fluorescence polarisation assay	kd	0.1560	uM
(4S)-4-acetamido-5-[2-aminoethylsulfonyl-[2-[[(2S)-1-[[2-[[(2S)-1-[[2-[[1-[2-aminoethylsulfonyl-[2-[[(2R)-1-[[2-[[(2S)-1-[2-aminoethylsulfonyl-[2-[[(2S)-1-[[2-[[(2S)-1-[[2-[[(2S)-1-[[2-[[(2S)-1-[(2-amino-2-oxoethyl)-benzylsulfanylamino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-(2-methylpropylsulfonyl)amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]propan-2-yl]amino]-2-oxoethyl]-(2-methylpropylsulfonyl)amino]-5-(diaminomethylideneamino)pentan-2-yl]amino]-2-oxoethyl]amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-(2-methylpropylsulfonyl)amino]-3-hydroxybutan-2-yl]amino]-2-oxoethyl]amino]-4-methylpentan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]-5-(diaminomethylideneamino)pentan-2-yl]amino]-2-oxoethyl]-methylsulfonylamino]-5-(diaminomethylideneamino)pentan-2-yl]amino]-2-oxoethyl]amino]pentanoic acid	1924303: Binding affinity to human beta catenin assessed as dissociation constant	kd	0.1600	uM
2-[3-[(3S)-3-[[cyclopropyl-[[6-(1H-pyrazol-4-yl)-3-pyridinyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(3S)-3-hydroxypyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1600	uM
N-[2-[(2R)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1800	uM
N-[2-[(3R)-3-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1800	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3R)-3-[[cyclopropyl-[[6-(1H-pyrazol-4-yl)-3-pyridinyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1800	uM
2-[[2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanoyl]amino]acetic acid	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1900	uM
2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.1900	uM
2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2100	uM
1-cyclopropyl-3-[(3S)-1-[3-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)oxyphenyl]piperidin-3-yl]-1-[[4-(1H-pyrazol-4-yl)phenyl]methyl]urea	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2300	uM
N-(2-aminoethyl)-2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2500	uM
N-(2-aminoethyl)-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2500	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3R)-3-[[cyclopropyl-[[5-(1H-pyrazol-4-yl)-2-pyridinyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2500	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[6-(1H-pyrazol-4-yl)-3-pyridinyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2500	uM
2-methyl-2-[3-[1-[3-(4-propan-2-ylphenyl)phenyl]sulfonylpiperidin-3-yl]phenoxy]-N-[4-(trifluoromethyl)phenyl]sulfonylpropanamide	1966244: Binding affinity to full-length beta-catenin (1 to 781 residues) (unknown origin) assessed as dissociation constant by SPR assay	kd	0.2600	uM
2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-(2-hydroxyethyl)-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2700	uM
N-[2-[(2S)-2-(aminomethyl)piperidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2800	uM
methyl 2-[[2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanoyl]amino]acetate	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2900	uM
2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-N-[2-[(2S)-2-[(dimethylamino)methyl]pyrrolidin-1-yl]-2-oxoethyl]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2900	uM
N-[2-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-2-oxoethyl]-2-[3-[(3S)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.2900	uM
3-(4-chlorophenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	775767: Inhibition of human TCF4/ flag epitope-tagged beta-catenin (unknown origin) interaction transfected in human HCT116 cells after 24 hrs by beta-galactosidase/luciferase reporter gene assay	ic50	0.3000	uM
2-methyl-2-[3-[1-[3-(4-propan-2-ylphenyl)phenyl]sulfonylpiperidin-3-yl]phenoxy]-N-thiophen-2-ylsulfonylpropanamide	1966244: Binding affinity to full-length beta-catenin (1 to 781 residues) (unknown origin) assessed as dissociation constant by SPR assay	kd	0.3200	uM
N-[2-[(2S)-2-(aminomethyl)piperidin-1-yl]-2-oxoethyl]-2-[3-[(3R)-3-[[cyclopropyl-[[4-(1H-pyrazol-4-yl)phenyl]methyl]carbamoyl]amino]piperidin-1-yl]phenoxy]-2-methylpropanamide	2109720: Binding affinity to full length his-tagged human beta-catenin (1 to 781 residues) expressed in Escherichia coli DE3 assessed as dissociation constant by SPR analysis	kd	0.3200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lithium Chloride	decreases phosphorylation, increases localization, decreases reaction, increases expression, affects reaction (+7 more)	25
sodium arsenite	decreases ubiquitination, decreases expression, increases reaction, affects localization, decreases reaction (+4 more)	15
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, affects reaction, decreases expression, decreases reaction, increases reaction (+5 more)	15
bisphenol A	decreases reaction, affects localization, affects cotreatment, decreases expression, decreases phosphorylation (+6 more)	14
Resveratrol	affects binding, decreases reaction, affects cotreatment, decreases localization, increases phosphorylation (+13 more)	13
Arsenic Trioxide	affects expression, affects binding, affects reaction, decreases response to substance, increases reaction (+5 more)	12
Niclosamide	affects binding, increases stability, decreases reaction, increases expression, increases reaction (+5 more)	12
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases activity, increases expression, decreases ubiquitination, decreases expression, increases phosphorylation (+7 more)	8
Quercetin	decreases expression, affects binding, increases activity, decreases activity, decreases reaction (+4 more)	8
XAV939	increases expression, affects binding, affects localization, decreases phosphorylation, increases phosphorylation (+3 more)	7
SB 216763	decreases expression, decreases reaction, increases activity, increases expression, increases reaction (+2 more)	6
Decitabine	increases expression, affects localization, decreases reaction, decreases response to substance, decreases expression (+1 more)	6
Acetylcysteine	increases expression, affects localization, increases cleavage, decreases expression, affects binding (+3 more)	6
Indomethacin	decreases expression, affects binding, decreases reaction, increases phosphorylation, increases expression (+2 more)	6
Oxygen	decreases reaction, affects reaction, decreases activity, affects expression, affects cotreatment (+4 more)	6
trichostatin A	decreases reaction, affects cotreatment, affects expression, increases expression, affects localization	5
Chir 99021	decreases expression, decreases reaction, increases expression, affects expression, affects reaction	5
Arsenic	decreases reaction, affects localization, increases expression, increases activity, affects binding (+6 more)	5
Cisplatin	decreases expression, increases reaction, decreases response to substance, increases expression, affects expression (+2 more)	5
Curcumin	decreases expression, increases degradation, affects binding, decreases reaction, increases expression (+2 more)	5
Tobacco Smoke Pollution	affects expression, affects localization, decreases reaction, increases expression, affects binding (+1 more)	5
Tretinoin	increases expression, decreases expression, increases reaction, affects cotreatment, decreases reaction	5
Valproic Acid	affects expression, affects cotreatment, increases expression	5
sulindac sulfone	decreases expression, decreases reaction, increases expression	4
6-bromoindirubin-3’-oxime	decreases phosphorylation, increases expression, decreases reaction, increases reaction, affects cotreatment (+1 more)	4
NCX 4040	decreases reaction, increases cleavage, affects binding, decreases expression, increases localization	4
PKF115-584	affects binding, decreases reaction, decreases expression, increases expression	4
Acetaminophen	affects localization, affects binding, increases reaction, decreases expression, increases expression (+3 more)	4
Doxorubicin	increases acetylation, increases activity, decreases reaction, affects cotreatment, increases expression (+5 more)	4
Chlorpyrifos	affects localization, decreases expression, decreases reaction, affects expression, affects reaction (+1 more)	4

ChEMBL screening assays

361 unique, capped per target: 358 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2446174	Binding	Increase in axin1-beta-catenin interaction in human SW480 cells at 5 to 10 uM after 24 hrs by immunoprecipitation	Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells. — Bioorg Med Chem Lett
CHEMBL1002059	Functional	Inhibition of beta-casein expressed in human SW480 cells by luciferase reporter gene assay	Synthesis and antitumoral evaluation of indole alkaloid analogues containing an hexahydropyrrolo[1’,2’,3’:1,9a,9]imidazo[1,2-a]indole skeleton. — Bioorg Med Chem

Cellosaurus cell lines

2,367 cell lines: 2,338 cancer cell line, 12 finite cell line, 7 induced pluripotent stem cell, 4 conditionally immortalized cell line, 3 embryonic stem cell, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0008	Daudi	Cancer cell line	Male
CVCL_0025	Caco-2	Cancer cell line	Male
CVCL_0068	SK-MEL-1	Cancer cell line	Male
CVCL_0077	SNU-398	Cancer cell line	Male
CVCL_0139	AGS	Cancer cell line	Female
CVCL_0205	CC-LP-1	Cancer cell line	Female
CVCL_0218	COLO 205	Cancer cell line	Male
CVCL_0232	Caco-2/15	Cancer cell line	Male
CVCL_0233	Caco-2/TC-7	Cancer cell line	Male
CVCL_0291	HCT 116	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06520410	PHASE4	RECRUITING	Safety and Efficacy of 18 mm Short Vitrectomy Probe for Pediatric Vitreoretinal Surgeries
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia