WNT3 Gene

HGNC Family	Wingless-type MMTV integration site family (WNT), Endogenous ligands
Name	wingless-type MMTV integration site family, member 3
Description	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. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWNT3 (and its closely related ligand, WNT3A, often referred to as Wnt‐3a) plays a pivotal role in initiating canonical Wnt/β‐catenin signaling by promoting receptor internalization. In response to WNT3a, the receptor LRP6 is internalized via a caveolin‐dependent pathway, becomes phosphorylated, and recruits Axin—a series of events that culminate in β‐catenin stabilization and activation of downstream transcriptional programs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDiverse oncogenic contexts have revealed that WNT3 can drive tumor progression through multiple mechanisms. Exogenous WNT3a enhances the self‐renewal capacity of prostate cancer cells, increasing nuclear β‐catenin levels and upregulating stem cell markers, thereby promoting prostasphere formation. In HER2‐overexpressing breast cancer cells, WNT3 overexpression contributes to trastuzumab resistance by inducing an epithelial-to-mesenchymal transition and transactivating EGFR. Colorectal tumors, even those harboring APC or β‐catenin mutations, require elevated WNT3 levels to achieve sufficient β‐catenin signaling; similarly, context-dependent regulation of WNT3 expression has been observed in embryonal carcinoma and breast cancer cells. Additionally, mantle cell lymphoma demonstrates constitutive β‐catenin activity in association with increased WNT3 expression, while in non‐small cell lung cancer high WNT3 levels correlate with the upregulation of proliferative markers such as c-Myc and survivin, reduced apoptosis, and poorer clinical outcomes. In bladder urothelial carcinoma, oncogenic SPAG5 signals via the AKT/mTOR pathway to upregulate WNT3, thereby enhancing both tumor growth and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to its tumor-promoting roles, WNT3 can also exert growth-suppressive functions during development. In craniofacial morphogenesis, WNT3 is one of the Wnt genes localized within the clf1 locus—a region implicated in non-syndromic cleft lip and/or palate—suggesting it may influence facial process formation. Conversely, during cerebellar development, WNT3 functions as a novel inhibitor of granule cell progenitor proliferation and medulloblastoma growth by downregulating pro-proliferative Sonic Hedgehog target genes and by activating a non-canonical MAP kinase cascade involving ERK1/2 and ERK5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hideki Yamamoto, Hideyuki Komekado, Akira Kikuchi "}, {"type": "b", "children": [{"type": "t", "text": "Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2006.07.003"}], "href": "https://doi.org/10.1016/j.devcel.2006.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16890161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16890161"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hideki Yamamoto, Hiroshi Sakane, Hideki Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2008.04.015"}], "href": "https://doi.org/10.1016/j.devcel.2008.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18606139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18606139"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Isabelle Bisson, David M Prowse "}, {"type": "b", "children": [{"type": "t", "text": "WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2009.43"}], "href": "https://doi.org/10.1038/cr.2009.43"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19365403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19365403"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanyuan Wu, Charles Ginther, Juri Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of Wnt3 activates Wnt/β-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-12-0155-T"}], "href": "https://doi.org/10.1158/1541-7786.MCR-12-0155-T"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23071104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23071104"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Oksana Voloshanenko, Gerrit Erdmann, Taronish D Dubash, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3610"}], "href": "https://doi.org/10.1038/ncomms3610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24162018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24162018"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Masaru Katoh "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11788904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11788904"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Pascal Gelebart, Mona Anand, Hanan Armanious, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive activation of the Wnt canonical pathway in mantle cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-02-139212"}], "href": "https://doi.org/10.1182/blood-2008-02-139212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18787224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18787224"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "S K Abdeen, Z Salah, B Maly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wwox inactivation enhances mammary tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.115"}], "href": "https://doi.org/10.1038/onc.2011.115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21499303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21499303"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "J Y Liu, Q H Zeng, P G Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-018-0223-2"}], "href": "https://doi.org/10.1038/s41388-018-0223-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29662193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29662193"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Renato Menezes, Ariadne Letra, Ana H Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Studies with Wnt genes and nonsyndromic cleft lip and palate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.20720"}], "href": "https://doi.org/10.1002/bdra.20720"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20890934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20890934"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sandrine L Anne, Eve-Ellen Govek, Olivier Ayrault, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNT3 inhibits cerebellar granule neuron progenitor proliferation and medulloblastoma formation via MAPK activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0081769"}], "href": "https://doi.org/10.1371/journal.pone.0081769"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24303070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24303070"}]}]}]}
Synonyms	INT4, TETAMS
Proteins	WNT3_HUMAN
NCBI Gene ID	7473
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WNT3 has 7,057 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for WNT3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WNT3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WNT3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of WNT3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of WNT3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of WNT3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of WNT3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WNT3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of WNT3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WNT3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WNT3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of WNT3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WNT3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of WNT3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with WNT3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WNT3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WNT3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of WNT3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with WNT3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of WNT3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WNT3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WNT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WNT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with WNT3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with WNT3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WNT3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with WNT3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with WNT3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WNT3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving WNT3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WNT3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with WNT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with WNT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with WNT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with WNT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with WNT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with WNT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at WNT3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WNT3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WNT3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing WNT3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with WNT3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.