WNT3A

gene
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Summary

WNT3A (Wnt family member 3A, HGNC:15983) is a protein-coding gene on chromosome 1q42.13, encoding Protein Wnt-3a (P56704). 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 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region.

Source: NCBI Gene 89780 — RefSeq curated summary.

At a glance

  • GWAS associations: 5
  • Clinical variants (ClinVar): 182 total
  • Phenotypes (HPO): 6
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_033131

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:15983
Approved symbolWNT3A
NameWnt family member 3A
Location1q42.13
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000154342
Ensembl biotypeprotein_coding
OMIM606359
Entrez89780

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000284523, ENST00000948304

RefSeq mRNA: 1 — MANE Select: NM_033131 NM_033131

CCDS: CCDS1564

Canonical transcript exons

ENST00000284523 — 4 exons

ExonStartEnd
ENSE00001015348228050656228050921
ENSE00001015349228006998228007199
ENSE00001015350228058986228061271
ENSE00002426379228022667228022908

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 86.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1885 / max 15.3457, expressed in 98 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
89060.188598

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
placentaUBERON:000198786.63gold quality
right lungUBERON:000216768.32gold quality
upper lobe of left lungUBERON:000895267.63gold quality
olfactory segment of nasal mucosaUBERON:000538662.63gold quality
lungUBERON:000204862.14gold quality
skin of legUBERON:000151160.02gold quality
zone of skinUBERON:000001459.64gold quality
skin of abdomenUBERON:000141659.15gold quality
esophagus mucosaUBERON:000246956.62gold quality
lower esophagus mucosaUBERON:003583455.95gold quality
saliva-secreting glandUBERON:000104453.59gold quality
minor salivary glandUBERON:000183053.16gold quality
prostate glandUBERON:000236753.02gold quality
vaginaUBERON:000099648.41gold quality
tonsilUBERON:000237246.94silver quality
bone marrow cellCL:000209243.82gold quality
colonic epitheliumUBERON:000039741.59gold quality
esophagusUBERON:000104340.36gold quality
stromal cell of endometriumCL:000225540.11gold quality
sural nerveUBERON:001548839.63gold quality
adult mammalian kidneyUBERON:000008239.26silver quality
fallopian tubeUBERON:000388937.40gold quality
uterine cervixUBERON:000000236.81gold quality
bone marrowUBERON:000237136.75gold quality
right uterine tubeUBERON:000130236.63silver quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
ectocervixUBERON:001224936.40gold quality
cortex of kidneyUBERON:000122535.59gold quality
granulocyteCL:000009435.55gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no1.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

TargetRegulation
AXIN2Activation
CACNA1GActivation
LEF1Repression
TERTActivation

Upstream regulators (CollecTRI, top): ERG, FOXQ1, HNF1B, HNF4A, KDM5B, MSGN1, MSX2, SMAD1, STAT3, TBX6

miRNA regulators (miRDB)

72 targeting WNT3A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-103A-3P99.9869.141595
HSA-MIR-10799.9869.141595
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-128-3P99.9571.172484
HSA-MIR-216A-3P99.9571.192505
HSA-MIR-185-3P99.9567.011743
HSA-MIR-497-5P99.9271.832674
HSA-MIR-15A-5P99.9072.802787
HSA-MIR-15B-5P99.9072.782798
HSA-MIR-16-5P99.9072.802780
HSA-MIR-195-5P99.9072.812805
HSA-MIR-424-5P99.8971.902641
HSA-MIR-6838-5P99.8971.942690
HSA-MIR-3681-3P99.8870.462254
HSA-MIR-6857-5P99.8765.32985
HSA-MIR-449299.8768.253611
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-132199.8465.301811
HSA-MIR-4756-5P99.8464.981809
HSA-MIR-473999.8465.251832
HSA-MIR-76599.8468.242442
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-6763-5P99.7664.681767
HSA-MIR-6764-5P99.7567.892304
HSA-MIR-11181-3P99.7566.382205

Literature-anchored findings (GeneRIF, showing 40)

  • Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45 (PMID:11788904)
  • Clustered with WNT14 on 1q42. (PMID:11836627)
  • wnt3a-beta catenin signaling regulates LEF-1 gene expression (PMID:12052822)
  • CKI epsilon-dependent phosphorylation of Dvl enhances the formation of a complex of Dvl-1 with Frat-1 and this complex leads to the activation of Wnt-3a-induced accumulation of beta-catenin (PMID:12556519)
  • These results suggest that Wnt responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells. (PMID:12629517)
  • Results suggest that disabled-2 functions as a negative regulator of canonical Wnt signaling by stabilizing the beta-catenin degradation complex. (PMID:12805222)
  • Wnt3a may stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon (PMID:14722104)
  • Wnt/beta-catenin pathway activation by Wnt3a raised beta-catenin in monocytes & decreased migration thru a dermal microvascular endothelial cell layer. This was associated with specific monocyte adherence to endothelial cells after Wnt3a exposure. (PMID:16565323)
  • BMP-2 antagonizes Wnt-3a signaling in osteoblast progenitors by promoting an interaction between Smad1 and Dvl-1 that restricts beta-catenin activation (PMID:16621789)
  • ILK activity can modulate acute Wnt3a mediated beta-catenin phosphorylation, stabilization and nuclear activation in a PI3K-independent manner. (PMID:16799642)
  • Wnt-LRP5 signalling may play a role in the adaptation of bone to mechanical load in humans, and may explain some gender-related differences in bone mass (PMID:17137849)
  • Over-expression of the Wnt3a gene significantly enhances the ability of fibroblast feeder cells to support the undifferentiated growth of 3 different human embryonic stem cell lines. (PMID:17211448)
  • Wnt3A/5A can function as mesenchymal regulatory factors by providing instructive cues for the recruitment, maintenance, and differentiation of mesenchymal stem cells. (PMID:17458904)
  • Wnt3A treatment significantly activated human hepatic stellate cells, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells. (PMID:17544413)
  • These results suggest that Wnt signaling crosstalk and functional antagonism with the LRP5 co-receptor are key signaling regulators of mesenchymal stem cells maintenance and differentiation. (PMID:17546602)
  • Blockade of Wnt3a stimulation of IP(5) generation blocks beta-catenin accumulation (PMID:17595165)
  • Results identify a novel feedback mechanism by which Wnt, including Wnt3a, negatively regulates LRP6 at the mRNA level. (PMID:17698587)
  • These findings demonstrate a requirement of Wnt signaling for maintenance, proliferation, and survival of NP when cultured in neurosphere conditions. (PMID:17822920)
  • Wnt3a markedly reduced the forskolin-induced expression of RANKL, a target gene of PTH/cAMP/PKA. (PMID:17990294)
  • Our results suggest that Wnt/beta-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis. (PMID:18242164)
  • bone marrow sera from 21 multiple myeloma patients significantly suppressed Wnt3a-induced OPG expression and enhanced RANKL expression in osteoblasts in a DKK1-dependent manner (PMID:18305214)
  • effect of Wnt3a on bone disease and growth of multiple myeloma cells in vitro and in vivo (PMID:18344425)
  • study demonstrated that Wnt3a & Wnt5a can promote proliferation of HEK293 cells & inhibit serum starvation-induced apoptosis, which implies Wnt3a & Wnt5a can maintain survival of HEK293 cells under stress (PMID:18462958)
  • FGF antagonizes Wnt signaling by inhibiting Wnt-induced transcription and suggest that multiple mechanisms, including downregulation of TCFs and Wnt receptors, contribute to this effect. (PMID:18505824)
  • glutamine synthetase has a role in control of glutamate signalling through Wnt3A and steroid pathways in osteoblastic cells (PMID:18555765)
  • both Wnt5a and Wnt3a bound Ror2, only Wnt5a induced Ror2 homo-dimerization and tyrosine phosphorylation in U2OS human osteoblastic cells. (PMID:18615587)
  • Wnt3a and Wnt5a have roles in inducing BMP-4 and 6 expression in prostate cancer osteoblast differentiation (PMID:18632632)
  • essential role of Wnt3a in hepatocyte differentiation from hESCs; Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation (PMID:18719101)
  • the frequent loss of stromal TGF-beta type II receptor expression in prostate cancer can relieve the paracrine suppression of Wnt3a expression (PMID:18724388)
  • These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/beta-catenin signaling in normal melanocyte development. (PMID:19144919)
  • Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs. (PMID:19265664)
  • The presence of WNT3a completely prevents normal adipocyte differentaiton. (PMID:19351711)
  • Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration. (PMID:19523451)
  • Data show that mutated GPC3 lacking the GPI anchoring domain (sGPC3) significantly inhibited the in vivo growth, blocked Wnt signaling and Erk1/2 and Akt phosphorylation in tumors. (PMID:19816934)
  • Wnt3A treatment greatly enhanced the effect of LRP6 on T-cell factor/lymphoid enhance factor luciferase activity in human mammary epithelial cells (PMID:19881541)
  • Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors. (PMID:19887570)
  • Data demonstrate that the Wnt-beta-catenin signaling pathway is functional in platelets, and that a Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation. (PMID:19901330)
  • Wnt/beta-catenin pathway activation might upregulate DIXDC1 through a post-translational mechanism by inhibiting the ubiquitin-mediated degradation of the DIXDC1 protein. (PMID:20085589)
  • analysis of the frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6 (PMID:20093360)
  • Loss of CYLD instigates tumor growth in human cylindromatosis through a mechanism in which hyperubiquitination of polymerized Dvl drives enhancement of Wnt3/beta-catenin responses. (PMID:20227366)

Cross-species orthologs

9 orthologs

OrganismSymbolGene ID
danio_reriownt3aENSDARG00000058822
mus_musculusWnt3aENSMUSG00000009900
rattus_norvegicusWnt3aENSRNOG00000003039
drosophila_melanogasterWnt2FBGN0004360
drosophila_melanogasterWnt5FBGN0010194
drosophila_melanogasterWnt10FBGN0031903
caenorhabditis_elegansWBGENE00000857
caenorhabditis_elegansWBGENE00000858
caenorhabditis_eleganslin-44WBGENE00003029

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-3aP56704 (reviewed: P56704)

All UniProt accessions (1): P56704

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 embryonic mesoderm development and formation of caudal somites. Required for normal morphogenesis of the developing neural tube. Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro).

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. Homooligomer; disulfide-linked, leading to inactivation. Interacts with PORCN. Interacts with APCDD1 and WLS. Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the complex with LRP6. Interacts with glypican GPC3. Interacts with PKD1 (via extracellular domain). Interacts with FZD5.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Moderately expressed in placenta and at low levels in adult lung, spleen, and prostate.

Post-translational modifications. Palmitoleoylation by PORCN is required for efficient binding to frizzled receptors. Palmitoleoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoleoylated WNT3A from WLS in secretory vesicles. Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway, possibly by promoting disulfide bond formation and oligomerization. Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A. Disulfide bonds have critical and distinct roles in secretion and activity. Loss of each conserved cysteine in WNT3A results in high molecular weight oxidized Wnt oligomers, which are formed through inter-Wnt disulfide bonding.

Similarity. Belongs to the Wnt family.

Isoforms (2)

UniProt IDNamesCanonical?
P56704-11yes
P56704-22

RefSeq proteins (1): NP_149122* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR005817WntFamily
IPR009141Wnt3Family
IPR018161Wnt_CSConserved_site
IPR043158Wnt_CHomologous_superfamily

Pfam: PF00110

UniProt features (59 total): strand 18, helix 12, disulfide bond 11, mutagenesis site 7, turn 4, glycosylation site 2, signal peptide 1, chain 1, splice variant 1, site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
7DRTELECTRON MICROSCOPY2.2
7URDELECTRON MICROSCOPY2.92
7UREELECTRON MICROSCOPY3.19
8TZRELECTRON MICROSCOPY3.5

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P56704-F188.620.77

Antibody-complex structures (SAbDab): 27URD, 7URE

Functional residue map

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

Catalytic / active sites (1): 26–27 (cleavage; by tiki1 and tiki2)

Post-translational modifications (1): 209

Disulfide bonds (11): 205–212, 281–312, 297–307, 311–351, 327–342, 329–339, 334–335, 77–88, 128–136, 138–155, 203–217

Glycosylation sites (2): 87, 298

Mutagenesis-validated functional residues (7):

PositionPhenotype
87strongly reduced ability to stimulate wnt-responsive reporters; when associated with q-298.
209abrogates wls binding.
209complete loss of palmitoleoylation.
209no effect on palmitoleoylation and secretion; the threonine can functionally replace the serine.
298strongly reduced ability to stimulate wnt-responsive reporters; when associated with q-87.
334no signaling activity despite the presence of significant amounts of secreted monomeric wnt3a, exhibits dominant negativ
335no signaling activity despite the presence of significant amounts of secreted monomeric wnt3a, exhibits dominant negativ

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

IDPathway
R-HSA-201681TCF dependent signaling in response to WNT
R-HSA-3238698WNT ligand biogenesis and trafficking
R-HSA-373080Class B/2 (Secretin family receptors)
R-HSA-3772470Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4641262Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-4641263Regulation of FZD by ubiquitination
R-HSA-5340588Signaling by RNF43 mutants
R-HSA-9793380Formation of paraxial mesoderm
R-HSA-9832991Formation of the posterior neural plate
R-HSA-9834899Specification of the neural plate border
R-HSA-9856649Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 490 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_HEPATOCYTE_PROLIFERATION, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT

GO Biological Process (81): osteoblast differentiation (GO:0001649), in utero embryonic development (GO:0001701), positive regulation of cytokine production (GO:0001819), heart looping (GO:0001947), positive regulation of receptor internalization (GO:0002092), transcription by RNA polymerase II (GO:0006366), axon guidance (GO:0007411), heart development (GO:0007507), intracellular protein localization (GO:0008104), COP9 signalosome assembly (GO:0010387), positive regulation of gene expression (GO:0010628), negative regulation of neuron projection development (GO:0010977), spinal cord association neuron differentiation (GO:0021527), hippocampus development (GO:0021766), cell proliferation in forebrain (GO:0021846), Wnt signaling pathway involved in forebrain neuroblast division (GO:0021874), dorsal/ventral neural tube patterning (GO:0021904), hemopoiesis (GO:0030097), neuron differentiation (GO:0030182), extracellular matrix organization (GO:0030198), mammary gland development (GO:0030879), positive regulation of B cell proliferation (GO:0030890), cell proliferation in midbrain (GO:0033278), non-canonical Wnt signaling pathway (GO:0035567), skeletal muscle cell differentiation (GO:0035914), post-anal tail morphogenesis (GO:0036342), synaptic vesicle recycling (GO:0036465), B cell proliferation (GO:0042100), inner ear morphogenesis (GO:0042472), cell fate commitment (GO:0045165), fat cell differentiation (GO:0045444), myoblast differentiation (GO:0045445), negative regulation of fat cell differentiation (GO:0045599), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), somatic stem cell division (GO:0048103), positive regulation of mesodermal cell fate specification (GO:0048337), paraxial mesodermal cell fate commitment (GO:0048343), positive regulation of skeletal muscle tissue development (GO:0048643), positive regulation of collateral sprouting in absence of injury (GO:0048697)

GO Molecular Function (9): transcription coactivator activity (GO:0003713), signaling receptor binding (GO:0005102), frizzled binding (GO:0005109), cytokine activity (GO:0005125), protein domain specific binding (GO:0019904), co-receptor binding (GO:0039706), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), endocytic vesicle membrane (GO:0030666), early endosome membrane (GO:0031901), extracellular exosome (GO:0070062), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), Wnt-Frizzled-LRP5/6 complex (GO:1990851), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-6 pathways:

CategoryPathways
TCF dependent signaling in response to WNT3
Gastrulation3
Signaling by WNT2
GPCR ligand binding1
Signaling by WNT in cancer1
MITF-M-regulated melanocyte development1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
protein binding4
cellular anatomical structure3
cell differentiation2
intracellular organelle lumen2
synapse2
ossification1
chordate embryonic development1
cytokine production1
regulation of cytokine production1
positive regulation of gene expression1
positive regulation of multicellular organismal process1
embryonic heart tube morphogenesis1
determination of heart left/right asymmetry1
regulation of receptor internalization1
receptor internalization1
positive regulation of receptor-mediated endocytosis1
DNA-templated transcription1
axonogenesis1
neuron projection guidance1
animal organ development1
circulatory system development1
macromolecule localization1
protein-containing complex assembly1
gene expression1
regulation of gene expression1
positive regulation of macromolecule biosynthetic process1
regulation of neuron projection development1
neuron projection development1
negative regulation of cell projection organization1
cell differentiation in spinal cord1
dorsal spinal cord development1
central nervous system neuron differentiation1
pallium development1
limbic system development1
anatomical structure development1
forebrain development1
neural precursor cell proliferation1
Wnt signaling pathway1
forebrain neuroblast division1
dorsal/ventral pattern formation1

Protein interactions and networks

STRING

2818 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
WNT3ALRP6O75581998
WNT3ALRP5O75197998
WNT3AFZD1Q9UP38994
WNT3AFZD2Q14332981
WNT3AFZD8Q9H461954
WNT3ACTNNB1P35222949
WNT3AAPCDD1Q8J025949
WNT3ADVL1O14640928
WNT3AAXIN1O15169927
WNT3ARYKP34925925
WNT3ADKK1O94907908
WNT3AWIF1Q9Y5W5903
WNT3ARSPO1Q2MKA7901
WNT3AAXIN2Q9Y2T1887
WNT3AFZD4Q9ULV1882

IntAct

28 interactions, top by confidence:

ABTypeScore
WNT3AWLSpsi-mi:“MI:0915”(physical association)0.780
LRP6WNT3Apsi-mi:“MI:0407”(direct interaction)0.770
WNT3ALRP6psi-mi:“MI:0915”(physical association)0.770
WNT3WNT3Apsi-mi:“MI:0914”(association)0.640
FZD7LRP6psi-mi:“MI:0914”(association)0.620
FZD5tcdBpsi-mi:“MI:0915”(physical association)0.610
WNT3ACANXpsi-mi:“MI:0914”(association)0.530
APCDD1WNT3Apsi-mi:“MI:0915”(physical association)0.520
TRABD2BWNT3Apsi-mi:“MI:0194”(cleavage reaction)0.520
FZD7TRABD2Bpsi-mi:“MI:0914”(association)0.520
TRABD2BFZD7psi-mi:“MI:0914”(association)0.520
WNT3AFZD8psi-mi:“MI:0915”(physical association)0.500
FZD8WNT3Apsi-mi:“MI:0914”(association)0.500
NOTUMWNT3Apsi-mi:“MI:0197”(deacetylation reaction)0.440
FZD2WNT3Apsi-mi:“MI:0407”(direct interaction)0.440
WNT3AAFMpsi-mi:“MI:0915”(physical association)0.400
WNT3AFzd8psi-mi:“MI:0915”(physical association)0.400
WNT3AMANBApsi-mi:“MI:0914”(association)0.350
WNT3ALRP5psi-mi:“MI:0914”(association)0.350
SLC22A1FNDC10psi-mi:“MI:0914”(association)0.350

BioGRID (57): CANX (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), WNT3 (Affinity Capture-MS), PPP2R1B (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5B (Affinity Capture-MS), PPP2R5E (Affinity Capture-MS), FEM1B (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), WNT3 (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5B (Affinity Capture-MS), PPP2R5E (Affinity Capture-MS)

ESM2 similar proteins: A2AIR5, A5D8T8, A6QLN9, O18739, O35217, O35393, O54951, O75077, O75078, O75900, P27467, P28686, P42642, P49641, P56704, Q00961, Q01098, Q08DW9, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5R890, Q642A6, Q6P988, Q6PCB0, Q6UXF7, Q7TNS7, Q8NCF0, Q8R2Z5, Q8TCU5, Q91XD7, Q96CW9, Q96FT7, Q96HD1, Q96N03, Q9BZ11, Q9ESM2, Q9ESM3

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

26 interactions.

AEffectBMechanism
WNT3Aup-regulatesRYKbinding
WNT3A“up-regulates activity”LRP5binding
WNT3A“up-regulates activity”LRP6binding
WNT3A“up-regulates activity”FZD1binding
WNT3A“up-regulates activity”FZD3binding
WNT3A“up-regulates activity”DVL1
WNT3Aup-regulatesALPL
DKK1down-regulatesWNT3A
SOSTdown-regulatesWNT3A
WNT3Aup-regulatesFZD2binding
GPC4up-regulatesWNT3Abinding
WNT3Aup-regulatesFZD8binding
SOSTDC1“down-regulates activity”WNT3A
WNT3A“up-regulates activity”Frizzledbinding
PORCN“up-regulates activity”WNT3Apalmitoylation
WLS“up-regulates activity”WNT3Arelocalization
WNT3A“up-regulates quantity by stabilization”FBN1
ERG“up-regulates quantity by expression”WNT3A“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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:

PathwayPartnersFoldFDR
Class B/2 (Secretin family receptors)579.3×9e-08

GO biological processes:

GO termPartnersFoldFDR
canonical Wnt signaling pathway771.5×5e-10
Wnt signaling pathway639.9×4e-07
neuron differentiation533.4×1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance113
Likely benign60
Benign7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1023 predictions. Top by Δscore:

VariantEffectΔscore
1:228022906:AAGG:Adonor_loss1.0000
1:228022907:AGG:Adonor_loss1.0000
1:228022908:GGTA:Gdonor_loss1.0000
1:228022909:GTAT:Gdonor_loss1.0000
1:228022910:T:Gdonor_loss1.0000
1:228050919:CAGG:Cdonor_loss1.0000
1:228050921:GGTA:Gdonor_loss1.0000
1:228050922:G:Cdonor_loss1.0000
1:228050923:T:Adonor_loss1.0000
1:228007197:GTG:Gdonor_gain0.9900
1:228007200:GT:Gdonor_loss0.9900
1:228007202:G:GTdonor_loss0.9900
1:228007204:G:GGdonor_gain0.9900
1:228022661:CTGCA:Cacceptor_loss0.9900
1:228022662:TGCA:Tacceptor_loss0.9900
1:228022663:GCAG:Gacceptor_loss0.9900
1:228022664:CAGG:Cacceptor_loss0.9900
1:228022665:A:AGacceptor_gain0.9900
1:228022666:G:GGacceptor_gain0.9900
1:228050651:TACA:Tacceptor_loss0.9900
1:228050654:A:AGacceptor_gain0.9900
1:228050655:G:GAacceptor_gain0.9900
1:228050655:GCT:Gacceptor_gain0.9900
1:228007195:TGGTG:Tdonor_gain0.9800
1:228007196:GGTGG:Gdonor_gain0.9800
1:228007200:G:GGdonor_gain0.9800
1:228007203:A:AGdonor_gain0.9800
1:228016775:TGG:Tdonor_gain0.9800
1:228022666:GGTC:Gacceptor_gain0.9800
1:228050651:TACAG:Tacceptor_gain0.9800

AlphaMissense

2306 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:228022762:G:AC56Y1.000
1:228022824:T:AC77S1.000
1:228022825:G:CC77S1.000
1:228022826:C:GC77W1.000
1:228022851:T:AW86R1.000
1:228022851:T:CW86R1.000
1:228022853:G:CW86C1.000
1:228022853:G:TW86C1.000
1:228022858:G:AC88Y1.000
1:228022859:C:GC88W1.000
1:228050682:G:CA114P1.000
1:228050798:G:CW152C1.000
1:228050798:G:TW152C1.000
1:228050848:T:GF169C1.000
1:228050903:C:AN187K1.000
1:228050903:C:GN187K1.000
1:228050913:G:TG191W1.000
1:228059245:T:GF280C1.000
1:228059247:T:AC281S1.000
1:228059248:G:AC281Y1.000
1:228059248:G:CC281S1.000
1:228059295:T:AC297S1.000
1:228059296:G:CC297S1.000
1:228022719:T:AC42S0.999
1:228022720:G:CC42S0.999
1:228022761:T:AC56S0.999
1:228022761:T:CC56R0.999
1:228022762:G:CC56S0.999
1:228022763:C:GC56W0.999
1:228022800:G:CG69R0.999

dbSNP variants (sampled 300 via entrez): RS1000026843 (1:228013599 A>T), RS1000066759 (1:228008914 A>G), RS1000182727 (1:228030844 T>C), RS1000276301 (1:228019133 A>T), RS1000366662 (1:228059833 T>A,C,G), RS1000380136 (1:228024885 G>A), RS1000400741 (1:228029983 C>A), RS1000436733 (1:228053273 A>G), RS1000449178 (1:228018869 G>A), RS1000454573 (1:228037021 C>T), RS1000537972 (1:228008072 G>A), RS1000655760 (1:228008130 A>G), RS1000664638 (1:228058937 G>A,C), RS1000699529 (1:228058401 G>A), RS1000716586 (1:228023424 G>A)

Disease associations

OMIM: gene MIM:606359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPOTerm
HP:0000939Osteoporosis
HP:0001288Gait disturbance
HP:0002653Bone pain
HP:0002757Recurrent fractures
HP:0002808Kyphosis
HP:0002953Vertebral compression fracture

GWAS associations

5 associations (top):

StudyTraitp-value
GCST004280_9Diastolic blood pressure2.000000e-16
GCST007930_8Medication use (agents acting on the renin-angiotensin system)3.000000e-10
GCST008362_97Birth weight2.000000e-09
GCST008839_18Height3.000000e-18
GCST90092003_2Alcohol-related hepatocellular carcinoma1.000000e-08

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0006336diastolic blood pressure
EFO:0009931Agents acting on the renin-angiotensin system use measurement
EFO:0004344birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1255137 (SINGLE PROTEIN), CHEMBL6066542 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,238 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL3188386WNT-97421,238

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

Binding affinities (BindingDB)

516 measured of 536 human assays (536 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2-fluoro-5-methyl-4-(2-methylpyridin-4-yl)phenyl)acetamideIC500.04 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-(3-fluorophenyl)-2-pyridinyl]-2-[6-(2-methyl-4-pyridinyl)-3-pyridinyl]acetamideIC500.06 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-methyl-4-pyridinyl)phenyl]-N-(5-pyridin-3-yl-2-pyridinyl)acetamideIC500.07 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[6-(2-methyl-4-pyridinyl)-3-pyridinyl]-N-(6-phenylpyridazin-3-yl)acetamideIC500.08 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[3-methyl-4-(2-methyl-4-pyridinyl)phenyl]-N-(5-pyridin-2-yl-2-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-pyridazin-4-yl-3-(trifluoromethyl)phenyl]-N-(5-pyridin-2-yl-2-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(pyrazin-2-yl)pyridin-2-yl)-2-(4-(pyridazin-4-yl)-3-(trifluoromethyl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-(3-fluorophenyl)-2-pyridinyl]-2-(4-pyridazin-4-ylphenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-methyl-4-pyridinyl)-3-(trifluoromethyl)phenyl]-N-(5-pyridin-2-yl-2-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
Methyl 4-(6-(2-(4-(2-methylpyridin-4-yl)phenyl)acetamido)pyridin-3-yl)piperazine-1-carboxylateIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(3-methyl-4-pyridazin-4-ylphenyl)-N-(5-pyrazin-2-yl-2-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
methyl 4-[6-[[2-[5-methyl-6-(2-methyl-4-pyridinyl)-3-pyridinyl]acetyl]amino]-3-pyridinyl]piperazine-1-carboxylateIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
methyl 4-[6-[[2-[3-methyl-4-(2-methyl-4-pyridinyl)phenyl]acetyl]amino]-3-pyridinyl]piperazine-1-carboxylateIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-methylpyridin-4-yl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-(4-acetylpiperazin-1-yl)-2-pyridinyl]-2-[3-chloro-4-(2-methyl-4-pyridinyl)phenyl]acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyridin-4-yl)-3-(trifluoromethyl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[3-cyano-4-(2-methyl-4-pyridinyl)phenyl]-N-(6-phenyl-3-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-fluoropyridin-4-yl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[3-cyano-4-(2-methyl-4-pyridinyl)phenyl]-N-(5-pyrazin-2-yl-2-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[3-cyano-4-(2-methyl-4-pyridinyl)phenyl]-N-(6-pyrazin-2-yl-3-pyridinyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(3-cyano-4-(2-methylpyridin-4-yl)phenyl)-N-(5-(pyridazin-3-yl)pyridin-2-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methoxy-4-(2-methylpyridin-4-yl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-chloro-2’-methyl-2,4’-bipyridin-5-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-[(3S)-4-acetyl-3-methylpiperazin-1-yl]-2-pyridinyl]-2-[3-cyano-4-(2-methyl-4-pyridinyl)phenyl]acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
propan-2-yl 4-[6-[[2-[5-methyl-6-(2-methyl-4-pyridinyl)-3-pyridinyl]acetyl]amino]-3-pyridinyl]piperazine-1-carboxylateIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2’-methyl-3-(trifluoromethyl)-2,4’-bipyridin-5-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2’-fluoro-3-methyl-2,4’-bipyridin-5-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(2’,3-difluoro-2,4’-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)-N-(5-(pyridazin-3-yl)pyridin-2-yl)acetamideIC500.1 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[6-(3-fluorophenyl)-3-pyridinyl]-2-[4-pyridazin-4-yl-3-(trifluoromethyl)phenyl]acetamideIC500.11 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-methylpyridin-4-yl)phenyl)acetamideIC500.11 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(3-methyl-4-pyridazin-4-ylphenyl)-N-(5-pyridin-2-yl-2-pyridinyl)acetamideIC500.12 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-methyl-4-pyridinyl)-3-(trifluoromethyl)phenyl]-N-(5-pyrazin-2-yl-2-pyridinyl)acetamideIC500.13 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-(3-fluorophenyl)-2-pyridinyl]-2-[5-methyl-6-(2-methyl-4-pyridinyl)-3-pyridinyl]acetamideIC500.13 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-methyl-4-pyridinyl)phenyl]-N-(6-phenylpyridazin-3-yl)acetamideIC500.14 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-methyl-4-pyridinyl)phenyl]-N-(5-pyridazin-3-yl-2-pyridinyl)acetamideIC500.15 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[5-(3-fluorophenyl)-2-pyridinyl]-2-[4-(2-methyl-4-pyridinyl)-3-(trifluoromethyl)phenyl]acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-[6-(3-fluorophenyl)-3-pyridinyl]-2-[6-(2-methyl-4-pyridinyl)-3-pyridinyl]acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-pyridazin-3-yl-2-pyridinyl)-2-[4-pyridazin-4-yl-3-(trifluoromethyl)phenyl]acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(2,3’-bipyridin-6’-yl)-2-(2’,3-dimethyl-2,4’-bipyridin-5-yl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
tert-butyl 4-(6-(2-(4-(2-methylpyridin-4-yl)phenyl)acetamido)pyridin-3-yl)piperazine-1-carboxylateIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-4-(2-methylpyridin-4-yl)phenyl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
ethyl 4-[6-[[2-[3-methyl-2-(2-methyl-4-pyridinyl)-2H-pyran-5-yl]acetyl]amino]-3-pyridinyl]piperazine-1-carboxylateIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-chloropyridin-4-yl)phenyl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-2’-methyl-2,4’-bipyridin-5-yl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-2’-methyl-2,4’-bipyridin-5-yl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyrimidin-4-yl)-3-(trifluoromethyl)phenyl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-(2’-fluoro-3-methyl-2,4’-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators
2-[4-(2-fluoro-4-pyridinyl)phenyl]-N-(5-pyrazin-2-yl-2-pyridinyl)acetamideIC500.2 nMUS-10251893: N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as Wnt signaling modulators

ChEMBL bioactivities

850 potent at pChembl≥5 of 927 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.40IC500.04nMCHEMBL5823795
10.22IC500.06nMCHEMBL6039603
10.15IC500.07nMCHEMBL5921303
10.10IC500.08nMCHEMBL6033847
10.00IC500.1nMCHEMBL5945646
10.00IC500.1nMCHEMBL5937289
10.00IC500.1nMCHEMBL6018741
10.00IC500.1nMCHEMBL5914153
10.00IC500.1nMCHEMBL6001502
10.00IC500.1nMCHEMBL6029730
10.00IC500.1nMCHEMBL5989592
10.00IC500.1nMCHEMBL4532746
10.00IC500.1nMCHEMBL5898705
10.00IC500.1nMCHEMBL5889799
10.00IC500.1nMCHEMBL5785948
10.00IC500.1nMCHEMBL5955254
10.00IC500.1nMCHEMBL5759987
10.00IC500.1nMCHEMBL5815787
10.00IC500.1nMCHEMBL5846874
10.00IC500.1nMCHEMBL6042520
10.00IC500.1nMCHEMBL5840741
10.00IC500.1nMCHEMBL5968250
10.00IC500.1nMCHEMBL5761075
10.00IC500.1nMCHEMBL6056464
10.00IC500.1nMCHEMBL6001723
10.00IC500.1nMCHEMBL5760694
10.00IC500.1nMCHEMBL4546441
10.00IC500.1nMCHEMBL5801448
10.00IC500.1nMCHEMBL5839562
10.00IC500.1nMCHEMBL5810452
9.96IC500.11nMCHEMBL6019535
9.96IC500.11nMCHEMBL5822915
9.92IC500.12nMCHEMBL6055708
9.89IC500.13nMCHEMBL5995349
9.89IC500.13nMCHEMBL6052903
9.85IC500.14nMCHEMBL5874786
9.82IC500.15nMCHEMBL5798889
9.70IC500.2nMCHEMBL5904878
9.70IC500.2nMCHEMBL5947565
9.70IC500.2nMCHEMBL5910225
9.70IC500.2nMCHEMBL4591963
9.70IC500.2nMCHEMBL5885074
9.70IC500.2nMCHEMBL5960615
9.70IC500.2nMCHEMBL5843321
9.70IC500.2nMCHEMBL5928809
9.70IC500.2nMCHEMBL5787107
9.70IC500.2nMCHEMBL5956303
9.70IC500.2nMCHEMBL5818081
9.70IC500.2nMCHEMBL4566038
9.70IC500.2nMCHEMBL6029645

PubChem BioAssay actives

49 with measured affinity, of 92 total; 49 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
1-(2-ethylphenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0013uM
3,5-dimethyl-1-(2-methylphenyl)-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0015uM
1-(2-bromophenyl)-5-methyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0023uM
N-(cyclopropylmethyl)-2-[4-(4-methoxybenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0035uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0036uM
5-methyl-1-(2-methylphenyl)-N-quinolin-2-yltriazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0041uM
8-[3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one1198342: Inhibition of ligand-induced WNT3A signaling in human PA-1 cells harboring TCF preincubated for 6 hrs before ligand addition measured after 24 hrs by luciferase reporter assayic500.0070uM
N-(cyclopropylmethyl)-2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0170uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-(2-methylpropyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0170uM
1-(2-bromophenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0210uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-propylacetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0340uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0400uM
3,5-dimethyl-1-(2-propan-2-ylphenyl)-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0480uM
1-(2-bromo-6-fluorophenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0500uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(pyridin-2-ylmethyl)acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0520uM
N-benzyl-2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0650uM
N-ethyl-2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0700uM
2-[4-(trifluoromethyl)phenyl]-3,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.0780uM
1-(2-fluorophenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0870uM
1-(2,5-dimethylphenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.0960uM
3,5-dimethyl-1-phenyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.1350uM
2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-methyl-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.1930uM
3-(2-fluorophenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.3040uM
1-(2-chlorophenyl)-3,5-dimethyl-N-quinolin-2-ylpyrazole-4-carboxamide1862157: Inhibition of recombinant human Wnt3a in HEK293 cells assessed as Wnt signalling by measuring reduction in relative luminescence units incubated for 24 hrs by luciferase reporter assayic500.3050uM
3-(4-fluorophenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.4830uM
3-(3-hydroxyphenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.8120uM
N-[(4-oxo-3H-quinazolin-2-yl)methyl]-3-phenyl-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic500.9370uM
2-[4-(2-hydroxypropan-2-yl)phenyl]-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.0300uM
4-chloro-5-cyano-N-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-methoxybenzamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.1000uM
2-[4-(trifluoromethoxy)phenyl]-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.2200uM
3-(4-hydroxyphenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.3500uM
2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.4100uM
2-[4-(trifluoromethyl)phenyl]-3H-quinazolin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.6700uM
2-[4-(trifluoromethyl)phenyl]-3,6,7,8-tetrahydrothiopyrano[3,2-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.7200uM
N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-3-phenyl-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic501.9200uM
2-[4-(trifluoromethyl)phenyl]-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic502.6500uM
methyl 4-(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)benzoate768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic503.0000uM
3-(2-hydroxyphenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic503.7700uM
2-(4-bromophenyl)-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic504.1400uM
2-[4-(dimethylamino)phenyl]-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic504.2100uM
2-(4-chlorophenyl)-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic504.4300uM
2-(4-methylphenyl)-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic504.6300uM
2-[4-(trifluoromethyl)phenyl]-4a,5,7,7a-tetrahydro-3H-thieno[3,4-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic505.0400uM
2-(4-methoxyphenyl)-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic505.0500uM
2-(4-methylsulfonylphenyl)-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic506.2900uM
3-(3-fluorophenyl)-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic506.6100uM
2-thiophen-3-yl-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic508.0900uM
N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-3-pyridin-4-yl-N-(thiophen-2-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic508.2500uM
N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]-3-phenyl-N-(thiophen-3-ylmethyl)propanamide768543: Inhibition of WNT3A signaling in HEK293 cells by luciferase reporter gene assay in presence of forskolinic508.5400uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Niclosamideaffects localization, decreases reaction, increases stability, decreases expression3
Chir 99021affects cotreatment, decreases expression, increases expression, increases reaction, affects binding2
XAV939decreases expression, increases expression, decreases reaction, affects binding, affects cotreatment2
Cadmiumdecreases expression, decreases reaction, increases abundance2
Silicon Dioxidedecreases expression2
abemaciclibdecreases expression1
ETC-159decreases expression1
aminomethylphosphonic acid (AMPA)decreases expression1
thymoquinonedecreases expression1
baicaleindecreases expression, decreases reaction1
bisphenol Aaffects expression1
ethyl-p-hydroxybenzoateincreases expression1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acidaffects methylation, increases abundance1
cypermethrinincreases expression1
cyfluthrinincreases expression1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamidedecreases reaction, increases expression1
taraxasterolincreases expression, decreases reaction1
deguelindecreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideincreases expression, increases reaction, affects cotreatment1
bavachinincreases expression, decreases reaction1
belinostatincreases expression1
(+)-JQ1 compounddecreases expression1
FV-429 compoundaffects cotreatment, decreases reaction, increases expression1
5-furan-2yl-isoxazole-3-carboxylic acid (3-imidazol-1yl-propyl)-amideaffects expression, affects reaction1
LGK974decreases expression1
Telmisartandecreases expression, decreases reaction1
Microplasticsincreases abundance, increases expression1
Matrinesdecreases expression1
Glyphosateincreases expression1
Ethanolaffects cotreatment, increases activity1

ChEMBL screening assays

31 unique, capped per target: 31 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1267283BindingInhibition of palmitoylation of Wnt3A expressed in mouse L cell by detergent solubility fractionation assessed as [3H]palmitate incorporation at 2.5 uM by autoradiography methodSmall molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. — Nat Chem Biol

Cellosaurus cell lines

8 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

CellosaurusNameCategorySex
CVCL_A7V7SEES3-1V human WNT3A, clone1Embryonic stem cellMale
CVCL_A7V8SEES3-1V human WNT3A, clone2Embryonic stem cellMale
CVCL_A7V9SEES3-1V human WNT3A, clone3Embryonic stem cellMale
CVCL_B8RUAbcam HCT 116 WNT3A KOCancer cell lineMale
CVCL_B9U8Abcam A-549 WNT3A KOCancer cell lineMale
CVCL_D8Y9Ubigene HCT 116 WNT3A KOCancer cell lineMale
CVCL_D9VTUbigene HEK293 WNT3A KOTransformed cell lineFemale
CVCL_E6SEGenomeditech CHO-K1 H_WNT3ASpontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hepatocellular carcinoma