WNT3

Summary

WNT3 (Wnt family member 3, HGNC:12782) is a protein-coding gene on chromosome 17q21.31-q21.32, encoding Proto-oncogene Wnt-3 (P56703). Ligand for members of the frizzled family of seven transmembrane receptors.

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region.

Source: NCBI Gene 7473 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tetraamelia syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 52
• Clinical variants (ClinVar): 6 total
• Phenotypes (HPO): 56
• Druggable target: yes
• MANE Select transcript: NM_030753

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12782
Approved symbol	WNT3
Name	Wnt family member 3
Location	17q21.31-q21.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC131950, MGC138321, MGC138323
Ensembl gene	ENSG00000108379
Ensembl biotype	protein_coding
OMIM	165330
Entrez	7473

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000225512, ENST00000572508, ENST00000573788, ENST00000576471, ENST00000706483, ENST00000706484, ENST00000706485, ENST00000706495, ENST00000867601, ENST00000931041

RefSeq mRNA: 1 — MANE Select: NM_030753 NM_030753

CCDS: CCDS11505

Canonical transcript exons

ENST00000225512 — 5 exons

Exon	Start	End
ENSE00000734129	46769783	46770048
ENSE00000734133	46768312	46768799
ENSE00001110660	46762506	46764621
ENSE00001110661	46818518	46818692
ENSE00002408906	46773668	46773909

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 87.70.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6115 / max 32.3320, expressed in 210 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166587	0.2550	103
166585	0.2527	123
166586	0.1038	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	87.70	gold quality
zone of skin	UBERON:0000014	85.94	gold quality
hypothalamus	UBERON:0001898	85.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.08	gold quality
anterior cingulate cortex	UBERON:0009835	84.97	gold quality
skin of leg	UBERON:0001511	84.48	gold quality
right frontal lobe	UBERON:0002810	83.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.21	gold quality
substantia nigra	UBERON:0002038	80.76	gold quality
right lobe of liver	UBERON:0001114	80.65	gold quality
cerebral cortex	UBERON:0000956	79.86	gold quality
frontal cortex	UBERON:0001870	79.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.38	gold quality
prefrontal cortex	UBERON:0000451	77.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.42	gold quality
liver	UBERON:0002107	76.12	gold quality
amygdala	UBERON:0001876	75.79	gold quality
temporal lobe	UBERON:0001871	75.72	gold quality
brain	UBERON:0000955	75.59	gold quality
superior frontal gyrus	UBERON:0002661	75.53	gold quality
nucleus accumbens	UBERON:0001882	75.35	gold quality
primary visual cortex	UBERON:0002436	74.56	gold quality
ventricular zone	UBERON:0003053	74.51	gold quality
Ammon’s horn	UBERON:0001954	74.05	gold quality
ganglionic eminence	UBERON:0004023	74.03	gold quality
stromal cell of endometrium	CL:0002255	73.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.98	gold quality
cortical plate	UBERON:0005343	72.54	gold quality
lower esophagus mucosa	UBERON:0035834	72.40	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
LMX1A	Activation

Upstream regulators (CollecTRI, top): ERG, POU5F1

miRNA regulators (miRDB)

155 targeting WNT3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-335-3P	99.93	73.36	4958

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45 (PMID:11788904)
• Wnt3 plays an important role in regulating characteristics and activity of stromal cells. (PMID:15588944)
• The Wnt-3a triggers the interaction of LRP6 with caveolin and promotes recruitment of Axin to LRP6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby inhibits the binding of beta-catenin to Axin. (PMID:16890161)
• an internally truncated LRP5 receptor is strongly implicated in deregulated activation of the WNT/beta-catenin signaling pathway in hyperparathyroid tumors (PMID:18044981)
• The results indicated that HBx induction in the CCL13-HBx stable cell line downregulated Wnt-3/beta-catenin expression and suppressed cell growth by repressing cell proliferation or triggering cell apoptosis. (PMID:18309246)
• a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/beta-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis. (PMID:18313787)
• CTLA-4 is a direct target of Wnt/beta-catenin signaling and is expressed in human melanoma tumors (PMID:18563180)
• WNT3 regulates distinct internalization pathways of LRP6 to tune the activation of beta catenin signaling. (PMID:18606139)
• mantle cell lymphoma highly and consistently expressed Wnt3 and Wnt10. (PMID:18787224)
• WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. (PMID:19365403)
• RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. (PMID:19421142)
• Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects. (PMID:19863181)
• Abnormalities of the Wnt3/3a pathway (located in the apical ectodermal ridge) include tetra-amelia and loss of the distal phalanges/nails. (PMID:20709709)
• Individuals carrying variant alleles in WNT3 presented an increased risk for cleft lip/palate (p = 0.0003; OR, 1.61; 95% CI, 1.29-2.02) in the Brazilian population studied. (PMID:20890934)
• Extracellular domain of FZD7 (sFZD7) was tested for its functional activity to interact with Wnt3, its ability to inhibit Wnt3-mediated signaling. (PMID:21314951)
• SNP rs415430 in the WNT3 gene was not associated with the risk of development of Parkinson disease (PMID:21789800)
• The apoptotic index was significantly lower in high-Wnt3 tumors than in low-Wnt3 tumors (P=0.0245). (PMID:22070884)
• The findings of a significant association between lip and/or palate clefts and two markers in the WNT3 and COL11A2 genes were the most consistent and were observed in all groups analysed and stratified. (PMID:22112025)
• study confirmed the involvement of polymorphisms in the WNT3 gene in NCL/P aetiology in the tested population. (PMID:22288914)
• Knockdown of Wnt3 by siRNA restored cytoplasmic expression of beta-catenin. (PMID:23071104)
• mRNA level of WNT3 in hESCs correlates with their definitive ectoderm differentiation efficiency. (PMID:24052941)
• Colorectal tumors express elevated levels of Wnt3 and GPR177. (PMID:24162018)
• WNT3 inhibits cerebellar granule neuron progenitor proliferation and medulloblastoma formation via MAPK activation. (PMID:24303070)
• WNT3 and WNT5B are critical factors, secreted from mesenchymal cancer cells, for instigating the epithelial cancer cell invasion. (PMID:24344732)
• Data show that the WNT/beta-CATENIN signaling cascade components, including WNT ligands WNT3 and WNT5A, is crucial for early odontogenesis. (PMID:24647585)
• Genome association study shows a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B in patients with classic bladder exstrophy. (PMID:24852367)
• WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish (PMID:26105184)
• WNT3 and membrane-associated beta-catenin regulate trophectoderm lineage differentiation in human blastocysts. (PMID:26108805)
• Two SNPs (rs3809857 and rs9890413) in the WNT3 gene were subjected to case-control and case-parent analysis (PMID:26505415)
• Wnt3 is associated with cholesterol-dependent domains (PMID:27463143)
• PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular basal cell carcinoma (PMID:27630294)
• analysis of WNT3 expression in CLL patients demonstrated that (i) untreated patients with more aggressive disease (with a notable exception of patients with 11q deletion) express less WNT3, (ii) WNT3 declines with disease progression in a significant proportion of patients and (iii) low WNT3 was identified as a strong independent marker indicating shorter treatment-free survival in CLL patients with IGHV mutation. (PMID:27651098)
• High expression of WNT3 is associated with hepatocellular carcinoma. (PMID:28586038)
• Demonstrate a significant change in miRNA profile dependent on the assisted reproductive technology outcome affecting Wnt pathway. (PMID:28971890)
• YAP maintains human embryonic stem cells pluripotency by preventing WNT3 expression in response to Activin, thereby blocking a direct route to embryonic cardiac mesoderm formation. (PMID:29269485)
• The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models. (PMID:29662193)
• Based on the findings of our current study, the rs3809857 and rs9890413 polymorphisms of WNT3 appeared to be associated with non-syndromic cleft lip (CL) with or without cleft palate (NSCL/P) . Limited evidence is found to support the association between other WNT3 polymorphisms and risk of NSCL/P. (PMID:30355643)
• Identification of candidate lncRNAs and circRNAs regulating WNT3/beta-catenin signaling in essential hypertension. (PMID:32392180)
• Concurrent Wnt pathway component expression in breast and colorectal cancer. (PMID:32534708)
• Circulating miR-374b-5p negatively regulates osteoblast differentiation in the progression of osteoporosis via targeting Wnt3 AND Runx2. (PMID:32548991)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt3	ENSDARG00000038990
mus_musculus	Wnt3	ENSMUSG00000000125
rattus_norvegicus	Wnt3	ENSRNOG00000003845

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Proto-oncogene Wnt-3 — P56703 (reviewed: P56703)

Alternative names: Proto-oncogene Int-4 homolog

All UniProt accessions (4): P56703, A0A9L9PXI5, A0A9L9PXJ3, A0A9L9PXK4

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. Required for normal gastrulation, formation of the primitive streak, and for the formation of the mesoderm during early embryogenesis. Required for normal formation of the apical ectodermal ridge. Required for normal embryonic development, and especially for limb development.

Subunit / interactions. Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids. Interacts with PORCN. Interacts with WLS.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.

Disease relevance. Tetraamelia syndrome 1 (TETAMS1) [MIM:273395] A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS1 patients manifest complete limb agenesis without defects of scapulae or clavicles. Other features include bilateral cleft lip/palate, diaphragmatic defect with bilobar right lung, renal and adrenal agenesis, pelvic hypoplasia, and urogenital defects. TETAMS1 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_110380* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR009141	Wnt3	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (39 total): disulfide bond 11, strand 11, helix 9, turn 3, glycosylation site 2, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6AHY	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56703-F1	88.73	0.71

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): 212

Disulfide bonds (11): 284–315, 300–310, 314–354, 330–345, 332–342, 337–338, 80–91, 131–139, 141–158, 206–220, 208–215

Glycosylation sites (2): 90, 301

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 496 (showing top): E2F_Q4, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, GOBP_AXIS_SPECIFICATION, GOBP_NEURON_PROJECTION_EXTENSION, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_HINDLIMB_MORPHOGENESIS, GCANCTGNY_MYOD_Q6, CMYB_01

GO Biological Process (35): cell morphogenesis (GO:0000902), mesoderm formation (GO:0001707), gamete generation (GO:0007276), axon guidance (GO:0007411), anterior/posterior axis specification (GO:0009948), dorsal/ventral axis specification (GO:0009950), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), positive regulation of Wnt signaling pathway (GO:0030177), neuron differentiation (GO:0030182), embryonic forelimb morphogenesis (GO:0035115), embryonic hindlimb morphogenesis (GO:0035116), cell fate commitment (GO:0045165), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of collateral sprouting in absence of injury (GO:0048697), negative regulation of axon extension involved in axon guidance (GO:0048843), regulation of neurogenesis (GO:0050767), Spemann organizer formation at the anterior end of the primitive streak (GO:0060064), canonical Wnt signaling pathway (GO:0060070), limb bud formation (GO:0060174), head morphogenesis (GO:0060323), mammary gland epithelium development (GO:0061180), cellular response to retinoic acid (GO:0071300), stem cell proliferation (GO:0072089), midbrain dopaminergic neuron differentiation (GO:1904948), regulation of mesenchymal stem cell differentiation (GO:2000739), multicellular organism development (GO:0007275), anatomical structure morphogenesis (GO:0009653), anterior/posterior pattern specification (GO:0009952), Wnt signaling pathway (GO:0016055), positive regulation of cell differentiation (GO:0045597), animal organ development (GO:0048513), anatomical structure formation involved in morphogenesis (GO:0048646), system development (GO:0048731), limb development (GO:0060173)

GO Molecular Function (6): frizzled binding (GO:0005109), cytokine activity (GO:0005125), protein domain specific binding (GO:0019904), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), endocytic vesicle membrane (GO:0030666), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), Wnt signalosome (GO:1990909), endoplasmic reticulum (GO:0005783), bounding membrane of organelle (GO:0098588)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	2
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axis specification	2
Wnt signaling pathway	2
cell differentiation	2
embryonic limb morphogenesis	2
protein binding	2
intracellular organelle lumen	2
anatomical structure morphogenesis	1
formation of primary germ layer	1
mesoderm morphogenesis	1
sexual reproduction	1
multicellular organismal reproductive process	1
axonogenesis	1
neuron projection guidance	1
anterior/posterior pattern specification	1
dorsal/ventral pattern formation	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of signal transduction	1
regulation of Wnt signaling pathway	1
generation of neurons	1
forelimb morphogenesis	1
hindlimb morphogenesis	1
cellular developmental process	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
collateral sprouting in absence of injury	1
positive regulation of collateral sprouting	1
regulation of collateral sprouting in absence of injury	1
negative regulation of axon extension	1
regulation of axon extension involved in axon guidance	1
axon extension involved in axon guidance	1
negative regulation of chemotaxis	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
Spemann organizer formation	1
limb morphogenesis	1

Protein interactions and networks

STRING

1640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT3	LRP5	O75197	984
WNT3	FZD8	Q9H461	937
WNT3	LRP6	O75581	929
WNT3	RYK	P34925	880
WNT3	FZD7	O75084	846
WNT3	CTNNB1	P35222	779
WNT3	FZD1	Q9UP38	749
WNT3	SFRP1	Q8N474	731
WNT3	MESD	Q14696	729
WNT3	FZD5	Q13467	717
WNT3	FZD6	O60353	697
WNT3	CRHR1	P34998	696
WNT3	FOXN1	O15353	693
WNT3	DKK1	O94907	690
WNT3	PORCN	Q9H237	690

IntAct

13 interactions, top by confidence:

A	B	Type	Score
WNT3	WNT3A	psi-mi:“MI:0914”(association)	0.640
FZD7	WNT3	psi-mi:“MI:0915”(physical association)	0.590
WNT3	FZD7	psi-mi:“MI:0915”(physical association)	0.590
Fzd8	WNT3	psi-mi:“MI:0407”(direct interaction)	0.560
WNT3	AFM	psi-mi:“MI:0915”(physical association)	0.540
WNT3	AFM	psi-mi:“MI:0407”(direct interaction)	0.540
WNT3A	CANX	psi-mi:“MI:0914”(association)	0.530
LRP6	WNT3	psi-mi:“MI:0407”(direct interaction)	0.440
WNT3A	LRP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): WNT3 (Affinity Capture-MS), WNT3 (Affinity Capture-MS), WNT3 (Affinity Capture-RNA), SLC9A8 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), WNT3A (Affinity Capture-MS), NEDD4L (Affinity Capture-Western)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A8MUP2, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, F1LTR1, O43688, O94925, P17553, P52875, P55244, P56703, P57791, Q16763, Q1RML1, Q28D01, Q2HJ61, Q3UHH2, Q3ZCD7, Q4L208, Q4R8V4, Q4V899, Q5R6I6, Q5R890, Q5SP67, Q66H54, Q86YN1, Q8BZH0, Q8BZI6, Q8K593, Q8R4D1, Q8VDI9, Q91ZH7, Q96H72, Q96NT3, Q9DAX2

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
WNT3	up-regulates	FZD3	binding
WNT3	up-regulates	LRP6	binding
WNT3	“up-regulates activity”	FZD7	binding
SOSTDC1	“down-regulates activity”	WNT3

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1474 predictions. Top by Δscore:

Variant	Effect	Δscore
17:46768796:TAGT:T	acceptor_gain	1.0000
17:46768800:C:CC	acceptor_gain	1.0000
17:46769778:CTCA:C	donor_loss	1.0000
17:46769779:TCAC:T	donor_loss	1.0000
17:46769780:CACCG:C	donor_loss	1.0000
17:46769781:A:AC	donor_gain	1.0000
17:46769781:ACC:A	donor_loss	1.0000
17:46769782:C:CA	donor_loss	1.0000
17:46769782:C:CC	donor_gain	1.0000
17:46773662:CAGTA:C	donor_loss	1.0000
17:46773664:GTA:G	donor_loss	1.0000
17:46773665:TACCT:T	donor_loss	1.0000
17:46773666:A:AT	donor_loss	1.0000
17:46773667:C:CT	donor_loss	1.0000
17:46768308:CTAC:C	donor_loss	0.9900
17:46768310:ACCTG:A	donor_loss	0.9900
17:46768322:A:AC	donor_gain	0.9900
17:46768323:C:CC	donor_gain	0.9900
17:46768326:G:A	donor_gain	0.9900
17:46768797:AGT:A	acceptor_gain	0.9900
17:46768797:AGTC:A	acceptor_loss	0.9900
17:46768798:GT:G	acceptor_gain	0.9900
17:46768798:GTC:G	acceptor_loss	0.9900
17:46768799:TC:T	acceptor_loss	0.9900
17:46768801:T:G	acceptor_loss	0.9900
17:46769777:GCTCA:G	donor_loss	0.9900
17:46769782:CCGTG:C	donor_gain	0.9900
17:46770046:TGG:T	acceptor_gain	0.9900
17:46770049:C:CC	acceptor_gain	0.9900
17:46773666:A:AC	donor_gain	0.9900

AlphaMissense

2334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:46768326:G:C	C354W	1.000
17:46768327:C:T	C354Y	1.000
17:46768328:A:G	C354R	1.000
17:46768363:C:G	C342S	1.000
17:46768364:A:T	C342S	1.000
17:46768375:C:G	C338S	1.000
17:46768375:C:T	C338Y	1.000
17:46768376:A:T	C338S	1.000
17:46768378:C:G	C337S	1.000
17:46768379:A:T	C337S	1.000
17:46768380:C:A	W336C	1.000
17:46768380:C:G	W336C	1.000
17:46768386:G:C	F334L	1.000
17:46768386:G:T	F334L	1.000
17:46768387:A:C	F334C	1.000
17:46768387:A:G	F334S	1.000
17:46768388:A:G	F334L	1.000
17:46768392:G:C	C332W	1.000
17:46768393:C:G	C332S	1.000
17:46768393:C:T	C332Y	1.000
17:46768394:A:T	C332S	1.000
17:46768399:C:G	C330S	1.000
17:46768400:A:T	C330S	1.000
17:46768443:A:C	C315W	1.000
17:46768444:C:G	C315S	1.000
17:46768444:C:T	C315Y	1.000
17:46768445:A:G	C315R	1.000
17:46768445:A:T	C315S	1.000
17:46768446:G:C	C314W	1.000
17:46768447:C:G	C314S	1.000

dbSNP variants (sampled 300 via entrez): RS1000013309 (17:46811720 C>T), RS1000016042 (17:46782504 G>A,T), RS1000154031 (17:46819393 G>T), RS1000236272 (17:46794709 C>T), RS1000246063 (17:46795031 G>A), RS1000270483 (17:46819865 TG>T), RS1000284334 (17:46779049 C>T), RS1000335817 (17:46784348 C>T), RS1000367011 (17:46784663 G>A), RS1000442686 (17:46789461 C>A,G), RS1000472876 (17:46811936 G>A,T), RS1000498857 (17:46774997 C>T), RS1000610416 (17:46781128 T>A), RS1000631499 (17:46767862 C>T), RS1000631844 (17:46807225 G>A,C)

Disease associations

OMIM: gene MIM:165330 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
tetraamelia syndrome 1	Definitive	Autosomal recessive
tetraamelia-multiple malformations syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
tetraamelia syndrome 1	Limited	AR

Mondo (2): tetraamelia syndrome 1 (MONDO:0060764), tetraamelia-multiple malformations syndrome (MONDO:0010110)

Orphanet (0):

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000042	Absent external genitalia
HP:0000046	Small scrotum
HP:0000068	Urethral atresia
HP:0000104	Renal agenesis
HP:0000148	Vaginal atresia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000293	Full cheeks
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000453	Choanal atresia
HP:0000482	Microcornea
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma
HP:0000648	Optic atrophy
HP:0000772	Abnormal rib morphology
HP:0000776	Congenital diaphragmatic hernia
HP:0000782	Abnormal scapula morphology
HP:0000889	Abnormal clavicle morphology
HP:0000921	Missing ribs
HP:0001195	Single umbilical artery
HP:0001274	Agenesis of corpus callosum
HP:0001543	Gastroschisis

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST001189_3	Parkinson’s disease	7.000000e-07
GCST001430_16	Parkinson’s disease	3.000000e-17
GCST002817_28	Alzheimer’s disease in APOE e4- carriers	6.000000e-06
GCST003262_39	Post bronchodilator FEV1	5.000000e-06
GCST003784_20	Multiple system atrophy	4.000000e-06
GCST004077_13	Cognitive function	8.000000e-08
GCST004601_147	Red blood cell count	5.000000e-18
GCST004604_31	Hematocrit	3.000000e-17
GCST004615_113	Hemoglobin concentration	6.000000e-16
GCST004862_113	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST005116_48	Male-pattern baldness	1.000000e-24
GCST005116_49	Male-pattern baldness	1.000000e-26
GCST005116_50	Male-pattern baldness	3.000000e-16
GCST005316_470	Intelligence (MTAG)	2.000000e-08
GCST005951_16	Body mass index	4.000000e-08
GCST006268_229	Reaction time	5.000000e-12
GCST006269_392	General cognitive ability	2.000000e-10
GCST006412_98	Intraocular pressure	2.000000e-10
GCST006414_36	Atrial fibrillation	3.000000e-12
GCST006481_10	Lung function (FEV1)	4.000000e-09
GCST006481_21	Lung function (FEV1)	1.000000e-09
GCST006481_33	Lung function (FEV1)	2.000000e-08
GCST006483_28	Lung function (FVC)	8.000000e-09
GCST006483_29	Lung function (FVC)	3.000000e-07
GCST006661_283	Male-pattern baldness	4.000000e-27
GCST006716_14	Alcohol use disorder (total score)	5.000000e-10
GCST007709_101	General factor of neuroticism	2.000000e-10
GCST007709_95	General factor of neuroticism	6.000000e-13
GCST008357_38	Mood instability	7.000000e-20
GCST008811_23	Alcohol consumption (drinks per week)	5.000000e-21

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004337	intelligence
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0008393	reaction time measurement
EFO:0004695	intraocular pressure measurement
EFO:0004312	vital capacity
EFO:0009458	alcohol use disorder measurement
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0009902	handedness
EFO:0008381	total cortical area measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536500	Tetraamelia multiple malformations (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6079 (SINGLE PROTEIN)

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

ChEMBL bioactivities

54 potent at pChembl≥5 of 56 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	EC50	30	nM	CHEMBL503825
7.22	EC50	60	nM	CHEMBL449276
7.05	EC50	90	nM	CHEMBL504979
7.05	EC50	90	nM	CHEMBL500903
7.05	EC50	90	nM	CHEMBL527086
6.92	EC50	120	nM	CHEMBL455476
6.80	EC50	160	nM	CHEMBL523726
6.80	EC50	160	nM	CHEMBL501433
6.72	EC50	190	nM	CHEMBL495526
6.70	EC50	200	nM	CHEMBL551506
6.68	EC50	210	nM	CHEMBL372397
6.64	EC50	230	nM	CHEMBL495534
6.64	EC50	230	nM	CHEMBL496581
6.62	EC50	240	nM	CHEMBL525899
6.60	EC50	250	nM	CHEMBL525718
6.60	EC50	250	nM	CHEMBL525970
6.57	EC50	270	nM	CHEMBL447079
6.55	EC50	280	nM	CHEMBL497383
6.55	EC50	280	nM	CHEMBL505036
6.51	EC50	310	nM	CHEMBL501332
6.51	EC50	310	nM	CHEMBL452196
6.50	EC50	320	nM	CHEMBL503281
6.46	EC50	350	nM	CHEMBL495535
6.46	EC50	350	nM	CHEMBL454478
6.42	EC50	380	nM	CHEMBL510748
6.40	EC50	400	nM	CHEMBL564783
6.35	EC50	450	nM	CHEMBL451431
6.34	EC50	460	nM	CHEMBL507695
6.21	EC50	620	nM	CHEMBL497177
6.19	EC50	650	nM	CHEMBL495575
6.15	EC50	710	nM	CHEMBL495536
6.14	EC50	720	nM	CHEMBL511077
6.10	EC50	800	nM	CHEMBL564714
6.08	EC50	830	nM	CHEMBL462363
6.00	EC50	1000	nM	CHEMBL550442
6.00	EC50	1000	nM	CHEMBL551249
6.00	EC50	1000	nM	CHEMBL551853
6.00	EC50	1000	nM	CHEMBL564772
6.00	EC50	1000	nM	CHEMBL563202
5.70	EC50	2000	nM	CHEMBL549349
5.70	EC50	2000	nM	CHEMBL556476
5.52	EC50	3000	nM	CHEMBL560712
5.52	EC50	3000	nM	CHEMBL564614
5.40	EC50	4000	nM	CHEMBL550764
5.30	EC50	5000	nM	CHEMBL563015
5.30	EC50	5000	nM	CHEMBL551505
5.05	EC50	9000	nM	CHEMBL552187
5.05	EC50	9000	nM	CHEMBL550093
5.00	EC50	1e+04	nM	CHEMBL563969
5.00	EC50	1e+04	nM	CHEMBL561779

PubChem BioAssay actives

54 with measured affinity, of 144 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-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]-N-tert-butylpyrrolidine-1-carboxamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.0300	uM
tert-butyl (2S)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]pyrrolidine-1-carboxylate	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.0600	uM
tert-butyl (2S)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]-5-oxopyrrolidine-1-carboxylate	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.0900	uM
(2S)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]-N-ethylpyrrolidine-1-carboxamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.0900	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(2-methylpropanoyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.0900	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(3,3-dimethylbutanoyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.1200	uM
5-(benzenesulfonyl)-N-[1-(2-morpholin-4-ylacetyl)piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.1600	uM
(2S)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]-N,N-dimethylpyrrolidine-1-carboxamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.1600	uM
5-(benzenesulfonyl)-N-[1-(2-pyrrolidin-1-ylacetyl)piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.1900	uM
4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]decan-4-yl]-N-quinolin-8-ylbenzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	0.2000	uM
tert-butyl (2R)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]pyrrolidine-1-carboxylate	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2100	uM
5-(benzenesulfonyl)-N-[1-(2-imidazol-1-ylacetyl)piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2300	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-methylpyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2300	uM
5-(benzenesulfonyl)-N-[1-[(2S)-5-oxopyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2400	uM
N-[1-[(2S)-1-acetylpyrrolidine-2-carbonyl]piperidin-4-yl]-5-(benzenesulfonyl)-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2500	uM
5-(benzenesulfonyl)-N-[1-(2-piperazin-1-ylacetyl)piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2500	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2700	uM
5-(benzenesulfonyl)-N-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2800	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(morpholine-4-carbonyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.2800	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-[2-(dimethylamino)acetyl]pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3100	uM
(2S)-2-[4-[[5-(benzenesulfonyl)-2-(trifluoromethyl)phenyl]sulfonylamino]piperidine-1-carbonyl]-N-phenylpyrrolidine-1-carboxamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3100	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(cyclohexylmethyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3200	uM
5-(benzenesulfonyl)-N-[1-[(2S)-pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3500	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(pyridine-4-carbonyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3500	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-benzoylpyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.3800	uM
4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-quinolin-8-ylcyclohexane-1-carboxamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	0.4000	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(3,3-dimethylbutyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.4500	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-(cyclohexanecarbonyl)pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.4600	uM
5-(benzenesulfonyl)-N-[1-[2-(methylamino)acetyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.6200	uM
5-(benzenesulfonyl)-N-piperidin-4-yl-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.6500	uM
5-(benzenesulfonyl)-N-[1-[(2R)-pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.7100	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-benzylpyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.7200	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(7-methylquinolin-8-yl)benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	0.8000	uM
5-(benzenesulfonyl)-N-[1-[(2S)-1-[4-(dimethylamino)benzoyl]pyrrolidine-2-carbonyl]piperidin-4-yl]-2-(trifluoromethyl)benzenesulfonamide	412786: Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	ec50	0.8300	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(4-methylquinolin-8-yl)cyclohexane-1-carboxamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	1.0000	uM
4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(7-methylquinolin-8-yl)cyclohexane-1-carboxamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	1.0000	uM
2-chloro-4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-quinolin-8-ylbenzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	1.0000	uM
N-(4-bromophenyl)-4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	1.0000	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(2-methoxyphenyl)benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	1.0000	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-[(1R,2R)-2-methoxycyclohexyl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	2.0000	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-2-methyl-N-quinolin-8-ylbenzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	2.0000	uM
N-(3,4-difluorophenyl)-4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	3.0000	uM
N-(4-chlorophenyl)-4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	3.0000	uM
4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(4-fluorophenyl)benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	4.0000	uM
4-[(1R,2R,6S,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-quinolin-8-ylbenzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	5.0000	uM
N-(3,4-dichlorophenyl)-4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	5.0000	uM
N-(3-bromophenyl)-4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	9.0000	uM
N-(2,4-difluorophenyl)-4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	9.0000	uM
4-[(1R,2S,6R,7S)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-quinolin-8-ylpiperidine-1-carboxamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	10.0000	uM
4-[(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl]-N-(5,6,7,8-tetrahydroquinolin-8-yl)benzamide	425205: Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	ec50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	decreases expression, increases expression	2
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
bufotalin	decreases reaction, increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
aflatoxin B2	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Niclosamide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

5 unique, capped per target: 3 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1012645	Functional	Antagonist activity at human WNT3 expressed in human U2OS cells assessed as Wnt signaling after 16 to 18 hrs by luciferase reporter gene assay	Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides. — J Med Chem
CHEMBL1032002	Binding	Inhibition of Wnt3 expressed in mouse L-cells assessed as inhibition of Wnt/catanin signaling pathway by luciferase reporter gene assay	Structure-activity relationship studies of small-molecule inhibitors of Wnt response. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8Y8	Ubigene HCT 116 WNT3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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