AXIN1

Summary

AXIN1 (axin 1, HGNC:903) is a protein-coding gene on chromosome 16p13.3, encoding Axin-1 (O15169). Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling.

This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8312 — RefSeq curated summary.

At a glance

• Gene–disease (curated): craniometadiaphyseal osteosclerosis with hip dysplasia (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 45
• Clinical variants (ClinVar): 184 total — 5 pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_003502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:903
Approved symbol	AXIN1
Name	axin 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R49
Ensembl gene	ENSG00000103126
Ensembl biotype	protein_coding
OMIM	603816
Entrez	8312

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000262320, ENST00000354866, ENST00000457798, ENST00000461023, ENST00000481769, ENST00000911683, ENST00000911684, ENST00000911685, ENST00000911686, ENST00000957925, ENST00000957926, ENST00000957927

RefSeq mRNA: 2 — MANE Select: NM_003502 NM_003502, NM_181050

CCDS: CCDS10405, CCDS10406

Canonical transcript exons

ENST00000262320 — 11 exons

Exon	Start	End
ENSE00000663689	291190	291297
ENSE00000663690	289440	289607
ENSE00001331290	346148	347106
ENSE00001736616	293488	293718
ENSE00001951737	352369	352723
ENSE00003474836	287440	288248
ENSE00003481928	309973	310069
ENSE00003576816	314543	314683
ENSE00003587187	297056	297226
ENSE00003634017	297722	298251
ENSE00003669225	304304	304441

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 93.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2601 / max 639.6168, expressed in 1785 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155720	7.6455	1730
155721	3.3240	1605
155719	0.2906	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.26	gold quality
mucosa of transverse colon	UBERON:0004991	89.83	gold quality
lower esophagus mucosa	UBERON:0035834	87.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.62	gold quality
gastrocnemius	UBERON:0001388	86.38	gold quality
cerebellar hemisphere	UBERON:0002245	86.11	gold quality
cerebellar cortex	UBERON:0002129	85.85	gold quality
transverse colon	UBERON:0001157	85.76	gold quality
leukocyte	CL:0000738	85.57	gold quality
skin of leg	UBERON:0001511	85.45	gold quality
muscle of leg	UBERON:0001383	85.38	gold quality
mononuclear cell	CL:0000842	85.26	gold quality
monocyte	CL:0000576	85.24	gold quality
cortical plate	UBERON:0005343	85.12	gold quality
skin of abdomen	UBERON:0001416	85.03	gold quality
blood	UBERON:0000178	84.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.85	gold quality
lower esophagus	UBERON:0013473	84.84	gold quality
popliteal artery	UBERON:0002250	84.68	gold quality
tibial artery	UBERON:0007610	84.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.17	gold quality
ganglionic eminence	UBERON:0004023	84.03	gold quality
aorta	UBERON:0000947	83.81	gold quality
right coronary artery	UBERON:0001625	83.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.63	gold quality
ventricular zone	UBERON:0003053	83.53	gold quality
upper lobe of left lung	UBERON:0008952	83.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.78
E-CURD-10	no	96.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, HOXB4, KLF8, LEF1, MYC, PDX1, SPI1, TCF7L2, TFAP2A

miRNA regulators (miRDB)

31 targeting AXIN1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-4800-5P	97.22	65.91	324

Literature-anchored findings (GeneRIF, showing 40)

• Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. (PMID:12000790)
• Overexpression of Icat induces G(2) arrest and cell death in tumor cell mutants for adenomatous polyposis coli, beta-catenin, or Axin. (PMID:12036951)
• 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)
• Data report the crystal structure of glycogen synthase kinase 3beta (GSK3beta) in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. (PMID:12554650)
• identification of mutations but not deletions in cerebellar medulloblastomas (PMID:12555076)
• In mice, ectopic expression of Axin1, an inhibitor of the Wnt signalling pathway, restricts haematopoietic stem cell (HSC) growth in vitro and reduces reconstitution in vivo. (PMID:12717450)
• Reduced expression of Axin correlates with tumour progression of esophageal squamous cell carcinoma (PMID:12771989)
• mutations of AXIN1 may play a limited role in tumorigenesis of cervical cancer (PMID:12883680)
• a tumor-associated mutation of the Axin gene is generally a rare event in pediatric neoplasms (PMID:14534723)
• The missense mutation rate is 11%, suggesting that Axin deficiency may contribute to the onset of colorectal tumorigenesis. (PMID:14566817)
• Axin binds directly to the export factor CRM1 in the presence of RanGTP (PMID:14630927)
• neither AXIN1 gene mutations nor AXIN1 locus LOH are involved in Wnt pathway activation in gastroesophageal junction adenocarcinomas (PMID:14970870)
• We also found that cyclin A/CDK2 phosphorylates Axin, thereby enhancing its association with beta-catenin. (PMID:15063782)
• In the presence of p53, the movement of Axin into & out of the Triton X-100-insoluble fraction is accelerated. p53 induces a faster mobilization of Axin into the degradation complex (PMID:15064706)
• Ccd1 drastically inhibited JNK activation both by Axin and by Dvl. (PMID:15262978)
• APC is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin (PMID:15355978)
• Axin acts as a tumor suppressor by facilitating p53 function (PMID:15526030)
• Axin forms homodimeric interactions through three domains, D, I, and DIX (PMID:15579909)
• Beta-catenin stabilization because of either beta-catenin or AXIN I mutation might be a late event for malignant progression rather than an early genetic event involving the initiation of HCC development. (PMID:15698401)
• No significant genetic alterations were found. (PMID:15981102)
• Axin1 gene may be one of the mutational target in oral SCC. (PMID:16163548)
• Axin and Arkadia cooperate with each other in promoting Smad7 ubiquitination. (PMID:16601693)
• Splice forms of crucial genes of the Wnt-pathway, beta-Catenin, LRP5, GSK3beta, Axin-1 and CtBP1 are expressed in human colorectal tissue. (PMID:16772034)
• findings raise the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with caudal duplication (PMID:16773576)
• These findings establish that the RGS domain of axin is able to directly interact with the alpha subunit of heterotrimeric G protein G12 and provide a unique tool to interdict Galpha12-mediated signaling processes. (PMID:16868183)
• Data show that P68 RNA helicase mediates platelet-derived growth factor-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. (PMID:17018282)
• AXIN1, AXIN2 and TCF7L2 may have roles in development of colorectal carcinomas [review] (PMID:17143297)
• 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)
• The activation of p38 was dependent on Axin and was required for the enhancement of mesenchymal stem cells differentiation by Wnt-4. (PMID:17720811)
• Reduced expression of axin is associated with the development of lung cancer (PMID:17768662)
• activation of Wnt signaling through AXIN1 rather than beta-catenin mutation might play an important role in liver carcinogenesis. (PMID:18171349)
• Mutations in AXIN1 and AXIN2 may contribute to gastric carcinogenesis. (PMID:18330950)
• Wnt dysregulation plays a role in prostatic tumourigenesis. Of particular interest, we identified three new potentially functionally relevant AXIN1 mutations (PMID:18514389)
• the C6 motif seems to reduce the interaction of Axin with Dvl-1. (PMID:18632848)
• A novel role for the tumour suppressor scaffold protein Axin1 in facilitating the formation of a degradation complex for c-Myc containing GSK3beta, Pin1, and PP2A-B56alpha is reported. (PMID:19131971)
• Zbed3 is a novel Axin-binding protein that is involved in Wnt/beta-catenin signaling modulation. (PMID:19141611)
• Results suggest that Axin modulates distribution of Axin-associated proteins in an expression level-dependent manner and these interactions affect the mitotic process. (PMID:19331826)
• Axin, but not Axin2, is involved in microtubule nucleation by forming a complex with gamma-tubulin at the centrosome. (PMID:19390532)
• Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway. (PMID:19513548)
• Reduced axin protein expression is associated with squamous cell carcinoma of esophagus. (PMID:19582507)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	axin1	ENSDARG00000102964
mus_musculus	Axin1	ENSMUSG00000024182
rattus_norvegicus	Axin1	ENSRNOG00000062714

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Axin-1 — O15169 (reviewed: O15169)

Alternative names: Axis inhibition protein 1

All UniProt accessions (5): O15169, A0A0S2Z4M1, A0A0S2Z4R0, A0A0S2Z4S3, H0Y830

UniProt curated annotations — full annotation on UniProt →

Function. Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation.

Subunit / interactions. Homodimer. Interacts with ZBED3; the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations. Component of the beta-catenin destruction complex, containing at least, CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination. Interacts with CTNNB1 (via the armadillo repeats 2-7). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction. Component of the AXIN1-HIPK2-TP53 complex. Interacts directly in the complex with TP53 and HIPK2. Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates ‘Ser-46’ phosphorylation of TP53 and induces cell death on UV irradiation. Also binds APC, SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; prevents interaction with MAP3K1. Interacts with MAP3K4. Interacts with ANKRD6 and AIDA. Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling. Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B. Interacts with PPP2CA; the interaction dephosphorylates AXIN1. Interacts with MACF1. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with TNKS. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. Interacts with WDR26. Interacts with GID8. Interacts with SIAH1 and SIAH2; both probably catalyze AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation. Interaction with GSK3B and AXIN1 is competitive.

Subcellular location. Cytoplasm. Nucleus. Membrane. Cell membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1. ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination at ‘Lys-48’ and subsequent activation of the Wnt signaling pathway. Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Sumoylation at Lys-857 and Lys-860 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription. Ubiquitination by SIAH1 and SIAH2 induces its proteasomal degradation as part of the activation of the Wnt signaling pathway.

Disease relevance. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The gene represented in this entry is involved in disease pathogenesis. Caudal duplication anomaly (CADUA) [MIM:607864] A condition characterized by the occurrence of duplications of different organs in the caudal region. The disease is caused by variants affecting the gene represented in this entry. Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter. Craniometadiaphyseal osteosclerosis with hip dysplasia (CMDOH) [MIM:620558] An autosomal recessive skeletal dysplasia characterized by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings include hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. Bone biopsy shows evidence of increased osteoblast and reduced osteoclast function at the growth plate resorption zone, leading to coarse trabeculae. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.

Isoforms (2)

UniProt ID	Names	Canonical?
O15169-1	1	yes
O15169-2	2

RefSeq proteins (2): NP_003493, NP_851393 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001158	DIX	Domain
IPR014936	Axin_b-cat-bd	Domain
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR032101	Axin_TNKS-bd	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR038207	DIX_dom_sf	Homologous_superfamily
IPR043581	Axin-like	Family
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615, PF00778, PF08833, PF16646

UniProt features (70 total): region of interest 14, helix 14, modified residue 9, sequence variant 7, strand 6, compositionally biased region 5, sequence conflict 3, turn 3, domain 2, cross-link 2, mutagenesis site 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
1DK8	X-RAY DIFFRACTION	1.57
7SXJ	X-RAY DIFFRACTION	1.85
1EMU	X-RAY DIFFRACTION	1.9
7SXF	X-RAY DIFFRACTION	1.94
8RU3	X-RAY DIFFRACTION	2
7SXH	X-RAY DIFFRACTION	2.09
4NM3	X-RAY DIFFRACTION	2.1
5WZZ	X-RAY DIFFRACTION	2.1
8RU4	X-RAY DIFFRACTION	2.13
4NM5	X-RAY DIFFRACTION	2.3
4NM7	X-RAY DIFFRACTION	2.3
8VME	X-RAY DIFFRACTION	2.3
1O9U	X-RAY DIFFRACTION	2.4
7SXG	X-RAY DIFFRACTION	2.4
8VMG	X-RAY DIFFRACTION	2.45
4NM0	X-RAY DIFFRACTION	2.5
4NU1	X-RAY DIFFRACTION	2.5
8VMF	X-RAY DIFFRACTION	2.5
7Y1P	X-RAY DIFFRACTION	2.6
3ZDI	X-RAY DIFFRACTION	2.65
4B7T	X-RAY DIFFRACTION	2.77
6JCK	X-RAY DIFFRACTION	3.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15169-F1	62.32	0.26

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 (11): 75, 77, 217, 469, 481, 486, 493, 511, 581, 857, 860

Mutagenesis-validated functional residues (2):

Position	Phenotype
383	loss of interaction with siah1. decreased siah1-induced proteasome-mediated ubiquitin-dependent degradation of axin1. no
385	loss of interaction with siah1. decreased siah1-induced proteasome-mediated ubiquitin-dependent degradation of axin1. no

Function

Pathways and Gene Ontology

Reactome pathways

36 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-4641257	Degradation of AXIN
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
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-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex
R-HSA-5689880	Ub-specific processing proteases
R-HSA-8931987	RUNX1 regulates estrogen receptor mediated transcription
R-HSA-8939256	RUNX1 regulates transcription of genes involved in WNT signaling
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-5467345	Deletions in the AXIN1 gene destabilize the destruction complex
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-212436	Generic Transcription Pathway
R-HSA-392499	Metabolism of proteins
R-HSA-4791275	Signaling by WNT in cancer
R-HSA-4839735	Signaling by AXIN mutants
R-HSA-4839743	Signaling by CTNNB1 phospho-site mutants
R-HSA-4839744	Signaling by APC mutants
R-HSA-4839748	Signaling by AMER1 mutants
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5688426	Deubiquitination

MSigDB gene sets: 409 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, TAATAAT_MIR126, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_AXIS_SPECIFICATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, BIOCARTA_GSK3_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (33): protein polyubiquitination (GO:0000209), in utero embryonic development (GO:0001701), nucleocytoplasmic transport (GO:0006913), apoptotic process (GO:0006915), sensory perception of sound (GO:0007605), dorsal/ventral axis specification (GO:0009950), negative regulation of gene expression (GO:0010629), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), cytoplasmic microtubule organization (GO:0031122), positive regulation of protein ubiquitination (GO:0031398), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), post-anal tail morphogenesis (GO:0036342), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), epigenetic programming in the zygotic pronuclei (GO:0044725), negative regulation of fat cell differentiation (GO:0045599), positive regulation of protein catabolic process (GO:0045732), positive regulation of JNK cascade (GO:0046330), axial mesoderm formation (GO:0048320), cell development (GO:0048468), negative regulation of protein metabolic process (GO:0051248), canonical Wnt signaling pathway (GO:0060070), head development (GO:0060322), protein-containing complex assembly (GO:0065003), negative regulation of canonical Wnt signaling pathway (GO:0090090), beta-catenin destruction complex assembly (GO:1904885), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), dorsal/ventral pattern formation (GO:0009953), Wnt signaling pathway (GO:0016055), protein catabolic process (GO:0030163), negative regulation of Wnt signaling pathway (GO:0030178), axial mesoderm development (GO:0048318), regulation of canonical Wnt signaling pathway (GO:0060828)

GO Molecular Function (18): p53 binding (GO:0002039), beta-catenin binding (GO:0008013), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein serine/threonine kinase activator activity (GO:0043539), SMAD binding (GO:0046332), molecular adaptor activity (GO:0060090), armadillo repeat domain binding (GO:0070016), I-SMAD binding (GO:0070411), R-SMAD binding (GO:0070412), protein serine/threonine kinase binding (GO:0120283), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515), protein domain specific binding (GO:0019904)

GO Cellular Component (15): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), microtubule cytoskeleton (GO:0015630), lateral plasma membrane (GO:0016328), beta-catenin destruction complex (GO:0030877), cytoplasmic vesicle (GO:0031410), perinuclear region of cytoplasm (GO:0048471), cell periphery (GO:0071944), Wnt signalosome (GO:1990909), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
Signaling by WNT	2
TCF dependent signaling in response to WNT	2
Signaling by AXIN mutants	2
Transcriptional regulation by RUNX1	2
Degradation of beta-catenin by the destruction complex	1
Signaling by WNT in cancer	1
Signaling by APC mutants	1
Signaling by AMER1 mutants	1
Deubiquitination	1
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	6
cellular anatomical structure	6
cytoplasm	4
protein ubiquitination	2
binding	2
SMAD binding	2
cell periphery	2
chordate embryonic development	1
nuclear transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
sensory perception of mechanical stimulus	1
axis specification	1
dorsal/ventral pattern formation	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
anatomical structure morphogenesis	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
epigenetic programming of gene expression	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1

Protein interactions and networks

STRING

3369 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AXIN1	LRP6	O75581	999
AXIN1	DVL1	O14640	999
AXIN1	LRP5	O75197	999
AXIN1	CTNNB1	P35222	999
AXIN1	GSK3B	P49841	999
AXIN1	CSNK1A1	P48729	998
AXIN1	GSK3A	P49840	996
AXIN1	APC	P25054	996
AXIN1	BTRC	Q9Y297	996
AXIN1	AMER1	Q5JTC6	995
AXIN1	ADAR	P55265	993
AXIN1	STK11	Q15831	991
AXIN1	ANKRD6	Q9Y2G4	991
AXIN1	CHKA	P35790	989
AXIN1	TCHP	Q9BT92	989

IntAct

429 interactions, top by confidence:

A	B	Type	Score
AXIN1	GSK3B	psi-mi:“MI:0407”(direct interaction)	0.980
GSK3B	AXIN1	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
AXIN1	GSK3B	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
AXIN1	GSK3B	psi-mi:“MI:0915”(physical association)	0.980
GSK3B	AXIN1	psi-mi:“MI:0915”(physical association)	0.980
AXIN1	GSK3B	psi-mi:“MI:0403”(colocalization)	0.980
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
AXIN1	CTNNB1	psi-mi:“MI:0914”(association)	0.940
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
AXIN1	APC	psi-mi:“MI:0407”(direct interaction)	0.850
AXIN1	APC	psi-mi:“MI:0914”(association)	0.850
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
AXIN1	AXIN1	psi-mi:“MI:0407”(direct interaction)	0.780
AMER1	AXIN1	psi-mi:“MI:0915”(physical association)	0.710

BioGRID (395): GNAS (Affinity Capture-Western), AXIN1 (Affinity Capture-Western), AXIN1 (Reconstituted Complex), GNAS (Reconstituted Complex), GSK3B (Affinity Capture-Western), AXIN1 (Affinity Capture-Western), AXIN1 (Affinity Capture-MS), AXIN1 (Affinity Capture-Luminescence), TP53 (Phenotypic Suppression), AXIN1 (Reconstituted Complex), HIPK2 (Affinity Capture-Western), AXIN1 (Affinity Capture-MS), AXIN1 (Affinity Capture-MS), AXIN1 (Affinity Capture-Western), AXIN1 (Proximity Label-MS)

ESM2 similar proteins: A0JNT9, A0JPP8, A1X157, O15169, O75145, O75335, P39880, P60469, Q07DZ5, Q08CF3, Q08E13, Q09YM8, Q2M1P5, Q2QLG9, Q2VUH7, Q32PN7, Q3TMW1, Q3UHC7, Q3UIL6, Q3UIW5, Q3UJV1, Q5DU25, Q5FWS6, Q5JU85, Q5PRF9, Q5XI59, Q5ZJ07, Q674X7, Q68UI8, Q69ZS8, Q6IPM2, Q6NZT2, Q6P402, Q6P730, Q6ZP65, Q80XS6, Q80Y83, Q8JZP9, Q8K1S6, Q8R4R9

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

55 interactions.

A	Effect	B	Mechanism
AXIN1	up-regulates	MAP3K4	binding
LRP6	“down-regulates activity”	AXIN1	relocalization
AXIN1	up-regulates	RNF111	binding
GNAS	up-regulates	AXIN1	binding
AXIN1	up-regulates	SMAD3
AXIN1	down-regulates	SMAD7	binding
MACF1	“down-regulates quantity by destabilization”	AXIN1
AXIN1	“up-regulates activity”	AXIN1	binding
DVL2	“up-regulates activity”	AXIN1	binding
WNT5A	down-regulates	AXIN1
AMER1	“up-regulates activity”	AXIN1	relocalization
TNKS	“down-regulates quantity by destabilization”	AXIN1	ubiquitination
TNKS2	“down-regulates quantity by destabilization”	AXIN1	ubiquitination
XAV939	up-regulates	AXIN1
AXIN1	down-regulates	BMPR1A	ubiquitination
GSK3B	up-regulates	AXIN1	phosphorylation
AXIN1	“form complex”	GSK3B/Axin/APC	binding
PPM1A	“down-regulates quantity by destabilization”	AXIN1	dephosphorylation
PPP1CC	“down-regulates activity”	AXIN1	dephosphorylation
PPP1CA	“down-regulates activity”	AXIN1	dephosphorylation
PPP1CB	“down-regulates activity”	AXIN1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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 GSK3beta mutants	5	77.7×	3e-07
CTNNB1 S33 mutants aren’t phosphorylated	5	77.7×	3e-07
CTNNB1 S37 mutants aren’t phosphorylated	5	77.7×	3e-07
CTNNB1 S45 mutants aren’t phosphorylated	5	77.7×	3e-07
CTNNB1 T41 mutants aren’t phosphorylated	5	77.7×	3e-07
Beta-catenin phosphorylation cascade	5	68.5×	5e-07
Disassembly of the destruction complex and recruitment of AXIN to the membrane	7	51.0×	3e-08
Degradation of beta-catenin by the destruction complex	7	24.7×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of protein catabolic process	5	15.2×	2e-03
canonical Wnt signaling pathway	6	13.7×	1e-03
positive regulation of canonical Wnt signaling pathway	5	11.5×	4e-03
negative regulation of canonical Wnt signaling pathway	6	10.6×	2e-03
Wnt signaling pathway	7	10.4×	1e-03
protein stabilization	8	8.0×	1e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	8	6.2×	3e-03
negative regulation of cell population proliferation	8	5.0×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — ESCA, GBM, HCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	108
Likely benign	26
Benign	16

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2627025	NM_003502.4(AXIN1):c.2503dup (p.Val835fs)	Pathogenic
2627027	NM_003502.4(AXIN1):c.2521C>T (p.Arg841Ter)	Pathogenic
4532251	NM_003502.4(AXIN1):c.2194C>T (p.Gln732Ter)	Pathogenic
6037	NM_003502.4(AXIN1):c.1085_1116del (p.Val362fs)	Pathogenic
6038	NG_012267.1:g.4590_5114|gom	Pathogenic

SpliceAI

3299 predictions. Top by Δscore:

Variant	Effect	Δscore
16:288246:TAT:T	acceptor_gain	1.0000
16:288247:AT:A	acceptor_gain	1.0000
16:288249:C:CC	acceptor_gain	1.0000
16:289438:A:AC	donor_gain	1.0000
16:289438:AC:A	donor_gain	1.0000
16:289438:ACCT:A	donor_loss	1.0000
16:289439:C:A	donor_loss	1.0000
16:289439:C:CA	donor_gain	1.0000
16:289439:CC:C	donor_gain	1.0000
16:289439:CCTGT:C	donor_gain	1.0000
16:289603:TTGTC:T	acceptor_gain	1.0000
16:289606:TC:T	acceptor_gain	1.0000
16:289607:CC:C	acceptor_gain	1.0000
16:289608:C:CC	acceptor_gain	1.0000
16:289608:CTGGG:C	acceptor_loss	1.0000
16:289609:T:A	acceptor_loss	1.0000
16:291188:A:AC	donor_gain	1.0000
16:291189:C:CC	donor_gain	1.0000
16:291189:CT:C	donor_gain	1.0000
16:293485:TACCT:T	donor_loss	1.0000
16:293486:A:AC	donor_gain	1.0000
16:293487:C:CA	donor_loss	1.0000
16:293487:C:CC	donor_gain	1.0000
16:293487:CCT:C	donor_gain	1.0000
16:293716:GACCT:G	acceptor_loss	1.0000
16:293720:T:C	acceptor_gain	1.0000
16:304299:CTCA:C	donor_loss	1.0000
16:304300:TCA:T	donor_loss	1.0000
16:304301:CACCA:C	donor_loss	1.0000
16:304302:A:C	donor_loss	1.0000

AlphaMissense

5640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:288144:C:T	G856D	1.000
16:288236:C:A	K825N	1.000
16:288236:C:G	K825N	1.000
16:288240:A:G	F824S	1.000
16:289473:A:G	F810S	1.000
16:304383:A:G	L392P	1.000
16:346424:A:G	F201S	1.000
16:346733:C:T	G98E	1.000
16:346734:C:A	G98W	1.000
16:346734:C:G	G98R	1.000
16:346734:C:T	G98R	1.000
16:346751:A:G	L92P	1.000
16:346771:C:A	W85C	1.000
16:346771:C:G	W85C	1.000
16:346773:A:G	W85R	1.000
16:346773:A:T	W85R	1.000
16:288145:C:G	G856R	0.999
16:288171:A:C	L847R	0.999
16:288171:A:T	L847Q	0.999
16:288200:A:C	F837L	0.999
16:288200:A:T	F837L	0.999
16:288202:A:G	F837L	0.999
16:288218:A:C	F831L	0.999
16:288218:A:T	F831L	0.999
16:288219:A:G	F831S	0.999
16:288220:A:G	F831L	0.999
16:288227:G:C	S828R	0.999
16:288227:G:T	S828R	0.999
16:288229:T:G	S828R	0.999
16:288238:T:C	K825E	0.999

dbSNP variants (sampled 300 via entrez): RS1000012511 (16:291401 G>T), RS1000078944 (16:291283 ACCT>A), RS1000089748 (16:290835 G>A,C), RS1000097705 (16:318952 G>A), RS1000174490 (16:293261 G>A), RS1000187661 (16:295336 C>T), RS1000262911 (16:353717 C>T), RS1000308527 (16:327442 C>G,T), RS1000319269 (16:299291 G>A), RS1000441048 (16:325176 C>G,T), RS1000482553 (16:335049 T>C), RS1000508105 (16:352706 C>G), RS1000516077 (16:313543 C>A,T), RS1000540748 (16:339539 A>G), RS1000580193 (16:298408 G>A)

Disease associations

OMIM: gene MIM:603816 | disease phenotypes: MIM:114550, MIM:620558, MIM:607864

GenCC curated gene-disease

Disease	Classification	Inheritance
craniometadiaphyseal osteosclerosis with hip dysplasia	Strong	Autosomal recessive
colorectal adenoma	Limited	Autosomal dominant
caudal duplication	Limited	Autosomal dominant

Mondo (4): hepatocellular carcinoma (MONDO:0007256), craniometadiaphyseal osteosclerosis with hip dysplasia (MONDO:0957832), caudal duplication (MONDO:0011928), colorectal adenoma (MONDO:0005484)

Orphanet (2): Hepatocellular carcinoma (Orphanet:88673), Caudal duplication (Orphanet:1756)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000073	Ureteral duplication
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000452	Choanal stenosis
HP:0000463	Anteverted nares
HP:0000520	Proptosis
HP:0000935	Thickened cortex of long bones
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001302	Pachygyria
HP:0001385	Hip dysplasia
HP:0001402	Hepatocellular carcinoma
HP:0001413	Micronodular cirrhosis
HP:0001442	Typified by somatic mosaicism
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0002684	Thickened calvaria
HP:0003015	Flared metaphysis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003762	Uterus didelphys
HP:0004482	Relative macrocephaly
HP:0004618	Sandwich appearance of vertebral bodies
HP:0005280	Depressed nasal bridge

GWAS associations

45 associations (top):

Study	Trait	p-value
GCST001482_33	Lumbar spine bone mineral density	1.000000e-16
GCST002783_12	Body mass index	1.000000e-07
GCST002783_457	Body mass index	2.000000e-06
GCST002783_492	Body mass index	2.000000e-07
GCST003388_3	Bone mineral density (spine)	5.000000e-10
GCST003388_6	Bone mineral density (spine)	5.000000e-08
GCST004601_135	Red blood cell count	2.000000e-09
GCST004602_223	Mean corpuscular volume	5.000000e-82
GCST004602_224	Mean corpuscular volume	5.000000e-14
GCST004605_13	Mean corpuscular hemoglobin concentration	1.000000e-46
GCST004605_14	Mean corpuscular hemoglobin concentration	7.000000e-14
GCST004621_183	Red cell distribution width	1.000000e-12
GCST004630_171	Mean corpuscular hemoglobin	3.000000e-102
GCST004630_172	Mean corpuscular hemoglobin	5.000000e-21
GCST005795_3	Femoral neck bone mineral density	1.000000e-09
GCST005796_27	Lumbar spine bone mineral density	6.000000e-09
GCST006288_169	Heel bone mineral density	2.000000e-08
GCST006288_337	Heel bone mineral density	6.000000e-11
GCST006288_443	Heel bone mineral density	2.000000e-16
GCST006979_947	Heel bone mineral density	1.000000e-30
GCST006979_948	Heel bone mineral density	2.000000e-09
GCST006979_949	Heel bone mineral density	9.000000e-24
GCST007014_12	Lumbar spine bone mineral density (trabecular)	5.000000e-07
GCST007015_20	Lumbar spine bone mineral density (integral)	3.000000e-06
GCST008839_236	Height	1.000000e-14
GCST010002_107	Refractive error	6.000000e-18
GCST010659_18	Waist circumference	5.000000e-07
GCST010659_19	Waist circumference	5.000000e-09
GCST010662_11	Systolic blood pressure	6.000000e-06
GCST010988_29	Adult body size	1.000000e-13

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007701	spine bone mineral density
EFO:0004305	erythrocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0007785	femoral neck bone mineral density
EFO:0009270	heel bone mineral density
EFO:0007620	volumetric bone mineral density
EFO:0006335	systolic blood pressure
EFO:0004459	ferritin measurement
EFO:0000714	survival time
EFO:1001480	metastatic colorectal cancer
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
C564315	Caudal Duplication Anomaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1255127 (SINGLE PROTEIN), CHEMBL3038464 (PROTEIN COMPLEX), CHEMBL3883307 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883308 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883309 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883310 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	3
perfluorooctane sulfonic acid	affects methylation, increases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	decreases methylation	1
nuciferine	affects reaction, decreases expression, affects cotreatment, increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
cupric chloride	increases expression	1
dibenzo(a,l)pyrene	decreases expression	1
beta-methylcholine	affects expression	1
AH 23848	affects cotreatment, increases reaction, affects binding	1
6-isopropoxy-9-oxoxanthene-2-carboxylic acid	increases reaction, affects binding, affects cotreatment	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
clothianidin	decreases expression	1
N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide	affects reaction, decreases expression, increases expression, decreases reaction	1
PKF115-584	decreases expression	1
(+)-JQ1 compound	increases expression	1
FV-429 compound	affects cotreatment, increases expression, increases reaction	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	affects binding, increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1267305	Binding	Induction of Axin1 stabilization in human DLD1 cells overexpressing IWR-IS by Western blot analysis	Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. — Nat Chem Biol

Cellosaurus cell lines

44 cell lines: 43 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0326	Hep 3B2.1-7	Cancer cell line	Male
CVCL_0364	JHH-5	Cancer cell line	Male
CVCL_0454	SNU-449	Cancer cell line	Male
CVCL_2956	HuH-1	Cancer cell line	Male
CVCL_3947	SNU-354	Cancer cell line	Male
CVCL_3948	SNU-368	Cancer cell line	Male
CVCL_B6FG	F6D2	Cancer cell line	Male
CVCL_B8BP	Abcam HCT 116 AXIN1 KO	Cancer cell line	Male
CVCL_B8SP	Abcam MCF-7 AXIN1 KO	Cancer cell line	Female
CVCL_B9DT	Abcam A-549 AXIN1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01767870	PHASE4	UNKNOWN	Efficacy Combined Fecal Immunochemical Test-Sigmoidoscopy for the Detection of Advanced Colorectal Neoplasia
NCT07167342	PHASE4	RECRUITING	The Effect of Oral Clostridium Butyricum on the Recurrence After Colonoscopic Resection of Colorectal Adenoma
NCT00168987	PHASE4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00554905	PHASE4	UNKNOWN	Radiofrequency Ablation With or With Transcatheter Arterial Embolization for Hepatocellular Carcinoma
NCT00555334	PHASE4	UNKNOWN	Nucleoid as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
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