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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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WNT3
Wnt family member 3
Chromosome 17 Β· 17q21.31-q21.32
NCBI Gene: 7473Ensembl: ENSG00000108379.12HGNC: HGNC:12782UniProt: P56703
77PubMed Papers
1Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Oncogene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of mesenchymal stem cell differentiationprotein bindingfrizzled bindingreceptor ligand activityTetraamelia syndrome 1
✦AI Summary

WNT3 is a secreted ligand that activates canonical Wnt signaling through frizzled receptor binding, leading to TCF/LEF transcription factor activation 1. During embryogenesis, WNT3 is essential for gastrulation, primitive streak formation, and mesoderm development, with particular importance for limb and apical ectodermal ridge formation 2. In postnatal tissues, WNT3 functions in stem cell maintenance and differentiation across multiple lineages. Within intestinal crypts, Paneth cells produce WNT3 as a critical niche signal supporting Lgr5+ stem cell self-renewal 3. WNT3 also regulates hindgut specification during intestinal development in concert with FGF signaling 4. During cardiac development, WNT3 expression is functionally important at embryonic and newborn stages 5. In liver regeneration, glutamate-reprogrammed macrophages activate WNT3 transcription to promote YAP1-dependent hepatocyte proliferation 6. Clinically, WNT3 dysfunction causes tetraamelia syndrome type 1. Aberrant WNT3 activation contributes to colorectal cancer pathogenesis, where p53-mediated WNT3 upregulation promotes cancer stem cell enrichment following 5-fluorouracil treatment 7.

Sources cited
1
WNT3 functions as a ligand in the canonical Wnt signaling pathway resulting in TCF/LEF transcription factor activation
PMID: 26902720
2
WNT3 is required for normal embryonic development, especially limb development and apical ectodermal ridge formation
PMID: 14872406
3
Paneth cells express WNT3 as an essential niche signal for Lgr5 stem cell maintenance in intestinal crypts
PMID: 21113151
4
WNT3A combined with FGF4 is required for hindgut specification during intestinal development
PMID: 21151107
5
WNT3 plays an essential functional role in cardiac development at embryonic and newborn stages
PMID: 33201861
6
Glutamate-reprogrammed macrophages activate WNT3 transcription to promote YAP1-dependent hepatocyte proliferation during liver regeneration
PMID: 40140584
7
p53-mediated WNT3 upregulation promotes cancer stem cell activation in colorectal cancer following 5-FU treatment
PMID: 33087710
Disease Associationsβ“˜1
Tetraamelia syndrome 1UniProt
Pathogenic Variants2
NM_030753.5(WNT3):c.271T>C (p.Cys91Arg)Likely pathogenic
Bladder exstrophy-epispadias-cloacal extrophy complex
β˜†β˜†β˜†β˜†2015β†’ Residue 91
NM_030753.5(WNT3):c.247C>T (p.Gln83Ter)Pathogenic
Tetraamelia syndrome 1
β˜†β˜†β˜†β˜†2004β†’ Residue 83
View on ClinVar β†—
Related Genes
PORCNProtein interaction98%CER1Protein interaction94%NOTUMProtein interaction94%WIF1Protein interaction92%FZD2Protein interaction92%LRP6Protein interaction92%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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WNT3PORCNCER1NOTUMWIF1FZD2LRP6
PROTEIN STRUCTURE
Preparing viewer…
PDB6AHY Β· 2.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.37Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.20 [0.11–0.37]
RankingsWhere WNT3 stands among ~20K protein-coding genes
  • #6,227of 20,598
    Most Researched77
  • #4,366of 5,498
    Most Pathogenic Variants2
  • #1,685of 17,882
    Most Constrained (LOEUF)0.37 Β· top 10%
Genes detectedWNT3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.
PMID: 21151107
Nature Β· 2011
1.00
2
Macrophages harness hepatocyte glutamate to boost liver regeneration.
PMID: 40140584
Nature Β· 2025
0.90
3
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.
PMID: 21113151
Nature Β· 2011
0.80
4
Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals.
PMID: 18983967
Cell Stem Cell Β· 2008
0.70
5
WNT3-WNT14B and WNT3A-WNT14 gene clusters (Review).
PMID: 12011973
Int J Mol Med Β· 2002
0.60