WNT5A Gene

HGNC Family	Wingless-type MMTV integration site family (WNT), Endogenous ligands
Name	wingless-type MMTV integration site family, member 5A
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 encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWNT5A is a multifaceted regulator in cancer, where its noncanonical signaling exerts context‐dependent effects on cell behavior. In melanoma and squamous cell carcinoma, WNT5A overexpression promotes cell motility and invasion by reorganizing the actin cytoskeleton, triggering PKC and Rac activation, and stimulating the formation of specialized structures that orient directional movement, while a switch from epithelial WNT4 to mesenchymal WNT5A accompanies EMT. In prostate cancer, elevated WNT5A correlates with higher Gleason scores and biochemical relapse, and activates signaling cascades—such as PKD‐dependent JNK activation leading to matrix metalloproteinase induction—that enhance invasive potential, although in a bone microenvironment it may also induce dormancy through upregulation of ubiquitin ligases. In thyroid carcinomas, paradoxically, WNT5A can antagonize canonical β‐catenin signaling via Ca²⁺/CaMKII pathways to reduce proliferation, migration, and invasion; similarly, in pancreatic cancer the transcription factor CUTL1 upregulates WNT5A to drive EMT and tumor progression, and in breast cancer WNT5A modulates Ca²⁺‐dependent NFAT signaling through counterregulatory cues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond tumorigenesis, WNT5A orchestrates critical developmental and tissue‐remodeling processes. In endothelial cells, noncanonical WNT5A signaling promotes angiogenesis by enhancing proliferation, migration, and survival as well as by regulating the expression of angiogenic modulators like MMP‐1 and Tie‐2. In glioblastoma, a PAX6/DLX5 transcriptional programme directs WNT5A‐mediated differentiation of cancer stem cells into endothelial‐like cells, contributing to neovascular niche formation that supports invasive growth. In osteoblastic cells, WNT5A engages receptor tyrosine kinase–like orphan receptor 2 (ROR2) to activate RTK‐like cascades that potentiate bone formation and mesenchymal stem cell differentiation. Moreover, in fibrotic conditions such as idiopathic pulmonary fibrosis and osteoarthritis, increased WNT5A enhances fibroblast proliferation, extracellular matrix production, and resistance to apoptosis, thereby contributing to pathologic tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWNT5A also plays an important role in immunomodulation and epigenetic regulation. In activated human macrophages, its expression is induced through Toll‐like receptor and NF‐κB signaling and helps regulate interleukin‐12 production and subsequent interferon‐γ release by T cells—thereby bridging innate and adaptive immunity. Epigenetic alterations such as promoter hypomethylation contribute to aberrant WNT5A expression in colorectal and prostate cancers, and regulation via the Ca²⁺‐sensing receptor further underscores the interplay between canonical and noncanonical pathways in modulating cell fate. Collectively, these findings highlight WNT5A as a critical signaling hub whose cellular effects—influencing migration, differentiation, immune responses, and tissue homeostasis—are finely tuned by context‐dependent interactions and epigenetic mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "26"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ashani T Weeraratna, Yuan Jiang, Galen Hostetter, et al. 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Synonyms	HWNT5A
Proteins	WNT5A_HUMAN
NCBI Gene ID	7474
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WNT5A has 15,224 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for WNT5A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WNT5A Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by WNT5A gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WNT5A 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 WNT5A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of WNT5A 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 WNT5A 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 WNT5A 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 WNT5A 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 WNT5A 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 WNT5A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WNT5A 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 WNT5A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WNT5A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with WNT5A 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 WNT5A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WNT5A 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 WNT5A 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 WNT5A gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WNT5A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WNT5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WNT5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with WNT5A 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 WNT5A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WNT5A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WNT5A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with WNT5A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with WNT5A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WNT5A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WNT5A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with WNT5A 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 WNT5A 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 WNT5A 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 WNT5A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with WNT5A 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 WNT5A 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 WNT5A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WNT5A 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 WNT5A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with WNT5A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with WNT5A gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of WNT5A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.