CTNNBIP1

Summary

CTNNBIP1 (catenin beta interacting protein 1, HGNC:16913) is a protein-coding gene on chromosome 1p36.22, encoding Beta-catenin-interacting protein 1 (Q9NSA3). Prevents the interaction between CTNNB1 and TCF family members, and acts as a negative regulator of the Wnt signaling pathway.

The protein encoded by this gene binds CTNNB1 and prevents interaction between CTNNB1 and TCF family members. The encoded protein is a negative regulator of the Wnt signaling pathway. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 56998 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 16 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_020248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16913
Approved symbol	CTNNBIP1
Name	catenin beta interacting protein 1
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	ICAT, MGC15093
Ensembl gene	ENSG00000178585
Ensembl biotype	protein_coding
OMIM	607758
Entrez	56998

Gene structure

Transcript identifiers

Ensembl transcripts: 59 — 59 protein_coding

ENST00000377256, ENST00000377258, ENST00000377263, ENST00000400904, ENST00000851117, ENST00000851118, ENST00000851119, ENST00000851120, ENST00000851121, ENST00000851122, ENST00000851123, ENST00000851124, ENST00000851125, ENST00000851126, ENST00000851127, ENST00000851128, ENST00000851129, ENST00000851130, ENST00000851131, ENST00000851132, ENST00000851133, ENST00000851134, ENST00000851135, ENST00000851136, ENST00000851137, ENST00000851138, ENST00000851139, ENST00000851140, ENST00000851141, ENST00000851142, ENST00000851143, ENST00000851144, ENST00000851145, ENST00000851146, ENST00000851147, ENST00000851148, ENST00000851149, ENST00000936601, ENST00000936602, ENST00000936603, ENST00000936604, ENST00000936605, ENST00000936606, ENST00000936607, ENST00000936608, ENST00000936609, ENST00000936610, ENST00000936611, ENST00000936612, ENST00000936613, ENST00000955026, ENST00000955029, ENST00000955031, ENST00000955032, ENST00000955033, ENST00000955034, ENST00000955035, ENST00000955036, ENST00000955037

RefSeq mRNA: 2 — MANE Select: NM_020248 NM_001012329, NM_020248

CCDS: CCDS106

Canonical transcript exons

ENST00000377263 — 6 exons

Exon	Start	End
ENSE00001267940	9871187	9871277
ENSE00001374198	9848276	9850776
ENSE00001473377	9910095	9910269
ENSE00001600669	9871969	9872088
ENSE00001643659	9877905	9877989
ENSE00001726112	9883705	9883738

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7585 / max 359.6161, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10251	18.6170	1808
10253	2.3365	985
10250	0.8667	600
10245	0.3044	50
10246	0.1926	72
10254	0.1650	81
10252	0.1548	52
10248	0.0573	16
10247	0.0469	13
10249	0.0172	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	98.92	gold quality
skin of abdomen	UBERON:0001416	98.78	gold quality
lower esophagus mucosa	UBERON:0035834	98.02	gold quality
zone of skin	UBERON:0000014	98.01	gold quality
esophagus mucosa	UBERON:0002469	96.83	gold quality
upper leg skin	UBERON:0004262	96.03	gold quality
upper arm skin	UBERON:0004263	95.67	gold quality
nipple	UBERON:0002030	94.42	gold quality
apex of heart	UBERON:0002098	94.10	gold quality
penis	UBERON:0000989	93.91	gold quality
skin of hip	UBERON:0001554	93.59	gold quality
cortical plate	UBERON:0005343	93.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
paraflocculus	UBERON:0005351	92.38	gold quality
cerebellar hemisphere	UBERON:0002245	92.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.35	gold quality
cerebellar cortex	UBERON:0002129	92.32	gold quality
minor salivary gland	UBERON:0001830	92.10	gold quality
corpus epididymis	UBERON:0004359	91.98	gold quality
cerebellum	UBERON:0002037	91.88	gold quality
mouth mucosa	UBERON:0003729	91.63	gold quality
saliva-secreting gland	UBERON:0001044	91.61	gold quality
ganglionic eminence	UBERON:0004023	91.28	gold quality
heart left ventricle	UBERON:0002084	91.14	gold quality
cardiac ventricle	UBERON:0002082	90.90	gold quality
cingulate cortex	UBERON:0003027	90.71	gold quality
anterior cingulate cortex	UBERON:0009835	90.58	gold quality
prefrontal cortex	UBERON:0000451	90.45	gold quality
right frontal lobe	UBERON:0002810	90.42	gold quality
esophagus	UBERON:0001043	90.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	236.41
E-ANND-3	yes	16.60
E-MTAB-10042	yes	9.33

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
GLI2	Unknown
MMP14	Unknown
STMN2	Unknown

Upstream regulators (CollecTRI, top): E2F1, HNF4A

miRNA regulators (miRDB)

71 targeting CTNNBIP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 40)

• stimulation of beta-catenin and suppression of gamma-catenin expression, occur within endometrial carcinomas with squamous differentiation (PMID:12068170)
• Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. (PMID:12124804)
• presentation of medulloblastoma in two siblings (one of each sex) and their great-uncle; immunostaining for gene products in medulloblastoma differed in the two siblings for beta-catenin and was similar with staining for gli. (PMID:12182422)
• Data report the elucidation of the crystal structure of ICAT, an inhibitor of beta-catenin-mediated transcription, bound to the armadillo repeat domain of beta-catenin. (PMID:12408825)
• ICAT’s primary role in beta-catenin signaling inhibition and further suggest that ICAT may have consequences for cadherin-based adhesive function in certain circumstances (PMID:14613891)
• We also found that cyclin A/CDK2 phosphorylates Axin, thereby enhancing its association with beta-catenin. (PMID:15063782)
• The comparison between Wilms tumors with and without CTNNB1 mutations revealed several target genes specifically deregulated in CTNNB1-mutated Wilms tumors (PMID:16575872)
• in motile cells beta-catenin is recruited by IQGAP1 and N-cadherin to active membrane ruffles, wherein beta-catenin mediates the internalization and possible recycling of the membrane-associated proteins N-cadherin and APC (PMID:17255093)
• The retained beta-catenin in cytoplasm by APC may be down-regulated by Axin 2, which is induced by beta-catenin/Tcf signaling. (PMID:17418091)
• Strategies targeting signals in the marrow microenvironment that amplify the Bcr-abl/VE-cadherin/beta-catenin axis may have utility in sensitizing drug-resistant leukemic stem cells. (PMID:17638851)
• Amyloid protein precursor induced phosphorylation of beta catenin, resulted in the reduction of total beta-catenin levels. (PMID:18070361)
• Beta-catenin expression is not reduced in laryngeal squamous expithelium of patients with laryngopharyngeal reflux. (PMID:18183411)
• Beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively, in hepatocellular tumors. (PMID:18433021)
• There was a direct relationship between tamoxifen exposure and overexpression of beta-catenin oncoprotein in endometrial adenocarcinoma. (PMID:18500270)
• In the gastric cancerous tissues, the expression percentage of Wnt-1, beta-catenin and E-cadherin is 54.4%, 45.6%, 47.2%, respectively, which is significantly higher than the percentage expression of these genes in normal tissues (p<0.01). (PMID:18705344)
• The matrix metalloproteinase-7 gene may be up-regulated by mutated or continuously elevated beta-catenin protein in sporadic desmoid tumors. (PMID:18715618)
• The presence of beta-catenin expression was detected in gastric tumors of the patients without distant metastases (PMID:18806748)
• adenomatous polyposis coli gene and nuclear b-catenin may have roles in wnt-related progression of invasive urothelial carcinomas (PMID:18844223)
• Results indicate that association of c-Jun, TCF$, and beta-catenin with a downstream enhancer element provides the principal regulation of c-Myc expression. (PMID:18852287)
• The CID domain of APC is required to down-regulate the transcriptional activity and the level of beta-catenin. (PMID:18854359)
• Increased expression in colorectal adenomas, high-grade intraepithelial neoplasia and adenocarcinomas than in the adjacent normal epithelia (PMID:18992165)
• The results suggest that WNT2 could act through its receptor FZD9 to regulate the beta-CATENIN pathway in cumulus cells, recruiting beta-CATENIN into plasma membranes and promoting the formation of adherens junctions involving CDH1. (PMID:19038973)
• decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors beta-catenin, USF2, and NFkappaB (PMID:19089909)
• ICAT expression was upregulated during NSC67657-induced differentiation of HL-60 cells. (PMID:19550115)
• Over-expression of ICAT was not sufficient to induce monocytic differentiation of HL60 cells; overexpression of ICAT enhanced differentiation of HL60 cells stimulated by all-trans retinoic acid or NSC67657. (PMID:19569129)
• beta-catenin-a marker of early stage of colorectal carcinogenesis, as well as TGF-beta1 and HIF-1alpha appear to be devoid of prognostic significance for colorectal cancer in this study of disease free survival (PMID:19898961)
• Reduced/aberrant beta-catenin expression was seen in benign and malignant salivary gland tumors. (PMID:20034989)
• Our results suggest that beta-catenin is useful for the prognosis evaluation of astrocytoma. (PMID:20182836)
• The results showed no differences in the expression of beta-catenin between tooth germs and solid and unicystic ameloblastomas. (PMID:20219600)
• overexpression of beta-catenin may be an important contributing factor to glioma progression. (PMID:20300972)
• The protein expression levels of Wnt1, beta-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas. (PMID:20809334)
• The results from the current study demonstrated the importance of the Wnt/beta-catenin signaling pathway in regulation of gene expression in hepatocellular carcinoma (PMID:20811694)
• our results support the concept that STAT3 upregulates the protein expression and transcriptional activity of beta-catenin in breast cancer. (PMID:20830236)
• cytoplasmic accumulation of beta-catenin can induce Tcf/Lef-mediated transcriptional activity, up-regulate MMP-7, and induce epithelial and mesenchymal transition (EMT). (PMID:20878057)
• beta-catenin is expressed in actinic chelitis and squamous cell carcinoma of the lip (PMID:20970365)
• Data show that elevated beta-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage IIB diseases. (PMID:21049553)
• LMP1 may be involved in nasopharyngeal carcinogenesis via beta-catenin signaling pathway (PMID:21336584)
• A coactivator role of CARM1 in the dysregulation of beta-catenin activity in colorectal cancer cell growth and gene expression (PMID:21478268)
• ICAT is a direct transcriptional target of E2F1, and activation of ICAT by E2F1 is required for E2F1 to inhibit beta-catenin activity. (PMID:21532622)
• When both E-cadherin and beta -catenin expressions were reduced, there was a significant unfavourable prognosis. (PMID:21574102)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctnnbip1	ENSDARG00000038954
mus_musculus	Ctnnbip1	ENSMUSG00000028988
rattus_norvegicus	Ctnnbip1	ENSRNOG00000016313
caenorhabditis_elegans		WBGENE00022885

Paralogs (1): LZIC (ENSG00000162441)

Protein

Protein identifiers

Beta-catenin-interacting protein 1 — Q9NSA3 (reviewed: Q9NSA3)

Alternative names: Inhibitor of beta-catenin and Tcf-4

All UniProt accessions (1): Q9NSA3

UniProt curated annotations — full annotation on UniProt →

Function. Prevents the interaction between CTNNB1 and TCF family members, and acts as a negative regulator of the Wnt signaling pathway.

Subunit / interactions. Binds CTNNB1.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the CTNNBIP1 family.

RefSeq proteins (2): NP_001012329, NP_064633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009428	ICAT_dom	Domain
IPR036911	ICAT_sf	Homologous_superfamily

Pfam: PF06384

UniProt features (5 total): helix 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1M1E	X-RAY DIFFRACTION	2.1
1T08	X-RAY DIFFRACTION	2.1
1LUJ	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSA3-F1	79.47	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 59

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex

MSigDB gene sets: 244 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, JAEGER_METASTASIS_DN, AREB6_03, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), branching involved in ureteric bud morphogenesis (GO:0001658), regulation of vascular permeability involved in acute inflammatory response (GO:0002528), anterior/posterior pattern specification (GO:0009952), negative regulation of Wnt signaling pathway (GO:0030178), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of monocyte differentiation (GO:0045657), positive regulation of osteoblast differentiation (GO:0045669), negative regulation of smooth muscle cell proliferation (GO:0048662), canonical Wnt signaling pathway (GO:0060070), negative regulation of transcription initiation by RNA polymerase II (GO:0060633), negative regulation of mesenchymal cell proliferation (GO:0072201), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of cell population proliferation (GO:0008285), Wnt signaling pathway (GO:0016055)

GO Molecular Function (5): transcription coactivator binding (GO:0001223), beta-catenin binding (GO:0008013), armadillo repeat domain binding (GO:0070016), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), beta-catenin destruction complex (GO:0030877), beta-catenin-ICAT complex (GO:1990711), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
Wnt signaling pathway	2
negative regulation of cell population proliferation	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
acute inflammatory response	1
regulation of vascular permeability	1
regionalization	1
negative regulation of signal transduction	1
regulation of Wnt signaling pathway	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
positive regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
negative regulation of transcription by RNA polymerase II	1
transcription initiation at RNA polymerase II promoter	1
regulation of transcription initiation by RNA polymerase II	1
negative regulation of DNA-templated transcription initiation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor signaling pathway	1
transcription coregulator binding	1
protein binding	1
protein domain specific binding	1

Protein interactions and networks

STRING

612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTNNBIP1	CTNNB1	P35222	974
CTNNBIP1	HNF4A	P41235	634
CTNNBIP1	LEF1	Q9UJU2	585
CTNNBIP1	LRP5	O75197	559
CTNNBIP1	CDH1	P12830	507
CTNNBIP1	TCF7L2	Q9NQB0	483
CTNNBIP1	DUSP2	Q05923	466
CTNNBIP1	DVL1	O14640	462
CTNNBIP1	AR	P10275	405
CTNNBIP1	KREMEN2	Q8NCW0	403
CTNNBIP1	H6PD	O95479	403
CTNNBIP1	GPR157	Q5UAW9	389
CTNNBIP1	AXIN1	O15169	385
CTNNBIP1	AXIN2	Q9Y2T1	373
CTNNBIP1	ACVR2A	P27037	372
CTNNBIP1	CLSTN1	O94985	372

IntAct

95 interactions, top by confidence:

A	B	Type	Score
CTNNBIP1	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.960
APC	CTNNB1	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.960
CTNNBIP1	CTNNB1	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
CTNNB1	CDH5	psi-mi:“MI:0915”(physical association)	0.930
CTNNB1	AR	psi-mi:“MI:0914”(association)	0.890
AR	CTNNB1	psi-mi:“MI:0914”(association)	0.890
JUP	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.810
CTNNBIP1	APC	psi-mi:“MI:0914”(association)	0.740
Ctnnb1	CTNNBIP1	psi-mi:“MI:0407”(direct interaction)	0.620
CTNNBIP1	Ctnnb1	psi-mi:“MI:0407”(direct interaction)	0.620
CTNNBIP1		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.560
REL	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.560
INCA1	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	CTNNBIP1	psi-mi:“MI:0915”(physical association)	0.560
CTNNBIP1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
CTNNBIP1	REL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): CTNNBIP1 (Two-hybrid), USHBP1 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), INCA1 (Two-hybrid), Ctnnb1 (Co-crystal Structure), CTNNB1 (Reconstituted Complex), BEND5 (Two-hybrid), CTNNBIP1 (Two-hybrid), CTNNBIP1 (Affinity Capture-Western), TK2 (Affinity Capture-MS), CTNNBIP1 (Affinity Capture-MS), APC (Affinity Capture-MS), BPGM (Affinity Capture-MS), CTNNA2 (Affinity Capture-MS)

ESM2 similar proteins: A0M8U1, A0PJN4, A1L167, A5PJI5, B7NC15, G3V9T7, O43681, O54984, O88761, P03730, P03736, P17427, P18484, P22706, P22708, P51583, P56812, P76347, P97834, Q0X0A5, Q13042, Q13098, Q1RLU8, Q2HJH9, Q2YDL1, Q3KNM2, Q3TXS7, Q3ZC24, Q5E9N2, Q5F418, Q5R5S4, Q5RB59, Q5TDH0, Q5ZJ41, Q6DGW9, Q6NRT5, Q8CFD0, Q8NFX7, Q8R349, Q8R3T5

Diamond homologs: Q28D79, Q54ID4, Q5E9N2, Q5PQN7, Q5ZKW2, Q6DHH7, Q8K3C3, Q8WZA0, Q9JJN6, Q9NSA3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CTNNBIP1	down-regulates	CTNNB1	binding
CTNNBIP1	“down-regulates activity”	CTNNB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Degradation of beta-catenin by the destruction complex	5	32.0×	2e-05
TCF dependent signaling in response to WNT	5	21.8×	9e-05
Diseases of signal transduction by growth factor receptors and second messengers	5	10.5×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell adhesion	5	14.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
638124	GRCh37/hg19 1p36.33-36.22(chr1:82154-11784118)x1	Pathogenic

SpliceAI

1581 predictions. Top by Δscore:

Variant	Effect	Δscore
1:9871182:CTCA:C	donor_loss	1.0000
1:9871183:TCACC:T	donor_loss	1.0000
1:9871184:CACCC:C	donor_loss	1.0000
1:9871185:A:AC	donor_gain	1.0000
1:9871185:AC:A	donor_gain	1.0000
1:9871186:C:CC	donor_gain	1.0000
1:9871186:CC:C	donor_gain	1.0000
1:9871275:CAG:C	acceptor_gain	1.0000
1:9871276:AG:A	acceptor_gain	1.0000
1:9871278:C:CC	acceptor_gain	1.0000
1:9871278:CTG:C	acceptor_loss	1.0000
1:9871966:CA:C	donor_loss	1.0000
1:9871967:A:AC	donor_gain	1.0000
1:9871967:ACG:A	donor_loss	1.0000
1:9871968:C:CA	donor_gain	1.0000
1:9871968:CG:C	donor_gain	1.0000
1:9871968:CGT:C	donor_gain	1.0000
1:9871968:CGTT:C	donor_gain	1.0000
1:9872084:GACTC:G	acceptor_gain	1.0000
1:9872086:CTC:C	acceptor_gain	1.0000
1:9872087:TC:T	acceptor_gain	1.0000
1:9872088:CC:C	acceptor_gain	1.0000
1:9872089:C:CC	acceptor_gain	1.0000
1:9872089:CT:C	acceptor_loss	1.0000
1:9872101:C:CT	acceptor_gain	1.0000
1:9872102:A:T	acceptor_gain	1.0000
1:9872110:C:CT	acceptor_gain	1.0000
1:9872111:A:T	acceptor_gain	1.0000
1:9910089:GCTTA:G	donor_loss	1.0000
1:9910090:CTTA:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000090783 (1:9883118 G>A), RS1000121087 (1:9866372 A>G), RS1000138706 (1:9864389 C>A,T), RS1000195035 (1:9866755 G>A,C), RS1000198497 (1:9898999 G>A,C,T), RS1000346137 (1:9861198 C>T), RS1000377762 (1:9849729 C>A,T), RS1000424119 (1:9864617 C>T), RS1000445626 (1:9855341 C>T), RS1000559935 (1:9864518 C>G,T), RS1000585427 (1:9907092 T>G), RS1000585928 (1:9870324 C>G,T), RS1000630475 (1:9879090 G>A), RS1000642328 (1:9876478 C>T), RS1000663763 (1:9858646 A>G,T)

Disease associations

OMIM: gene MIM:607758 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004068_54	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	6.000000e-06
GCST90002401_4	Platelet distribution width	3.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523468 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-N-propan-2-ylpyridin-3-amine	IC50	1.2 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]pyridin-3-amine	IC50	3.9 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethylpyridin-3-amine	IC50	6 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-N,N-dimethylmethanamine	IC50	13 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[3-fluoro-5-[2-(5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-7-yl]phenyl]-N’,N’-dimethylethane-1,2-diamine	IC50	21 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-1-[5-[3-(7-thiophen-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methanamine	IC50	48 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
3-[7-[3-fluoro-5-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-c]pyridin-2-yl]-5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridine	IC50	99 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-[3-fluoro-5-[2-(5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-7-yl]phenyl]-N,N-dimethylmethanamine	IC50	138 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
3-[7-[3-fluoro-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-3H-imidazo[4,5-c]pyridin-2-yl]-5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridine	IC50	263 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
(6S,9aS)-N-benzyl-6-(4-hydroxybenzyl)-8-(naphthalen-1-ylmethyl)-4,7-dioxooctahydro-1H-pyrazino[1,2-a]pyrimidine-1-carboxamide	IC50	7000 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Valproic Acid	decreases expression, increases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation	2
entinostat	decreases expression, affects cotreatment	2
Niclosamide	affects binding, decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
bruceine D	decreases expression, affects expression, affects reaction, increases expression, affects binding (+1 more)	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
XAV939	affects binding, decreases reaction	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Cocaine	decreases expression	1
Cyclophosphamide	affects cotreatment, affects expression	1
Doxorubicin	affects cotreatment, affects expression	1
Nickel	decreases expression	1
Oxygen	affects expression, affects reaction, decreases reaction, increases expression	1
Paraquat	increases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4362109	Binding	Effect on beta-catenin phosphorylation level in human NCI-H1975 incubated for 12 hrs by human phosphokinase proteome profiler array relative to control	Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1R3	HyCyte Ishikawa KO-hCTNNBIP1	Cancer cell line	Female

Clinical trials (associated diseases)

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