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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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WNT4
Wnt family member 4
Chromosome 1 · 1p36.12
NCBI Gene: 54361Ensembl: ENSG00000162552.16HGNC: HGNC:12783UniProt: P56705
125PubMed Papers
22Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of testicular blood vessel morphogenesiscanonical Wnt signaling pathwaynegative regulation of male gonad developmentmammary gland epithelium developmentmullerian aplasia and hyperandrogenismSERKAL syndromeMayer-Rokitansky-Küster-Hauser syndromeuterine fibroid
✦AI Summary

WNT4 is a signaling ligand that activates both canonical and non-canonical Wnt pathways, playing crucial roles in embryonic development and adult tissue homeostasis. In development, WNT4 is essential for nephron formation, where it drives the mesenchyme-to-epithelium transition during kidney development 1. It serves as a critical regulator of female reproductive development, controlling ovarian differentiation and Müllerian duct formation while antagonizing testosterone production 2. Beyond development, WNT4 maintains diverse physiological functions in adults. Non-canonical WNT4 signaling drives metabolic maturation of pancreatic β-cells, enabling glucose-stimulated insulin secretion 3. The protein promotes osteogenic differentiation of bone marrow mesenchymal stem cells through activation of the β-catenin pathway 4. However, WNT4 also contributes to pathological processes, including cardiac fibrosis following myocardial infarction through β-catenin/NF-κB signaling activation 5. Clinical significance is evident in reproductive health, where WNT4 mutations cause Müllerian aplasia with hyperandrogenism 2, and altered expression associates with endometrial cancer 6. Large-scale genetic studies confirm WNT4's importance across multiple female reproductive health conditions 7, highlighting its therapeutic potential for developmental disorders, metabolic diseases, and reproductive health conditions.

Sources cited
1
WNT4 drives mesenchyme-to-epithelium transition during nephron formation
PMID: 12386301
2
WNT4 regulates female reproductive development, ovarian differentiation, and antagonizes testosterone production
PMID: 18987495
3
Non-canonical WNT4 signaling drives metabolic maturation of pancreatic β-cells
PMID: 32814902
4
WNT4 promotes osteogenic differentiation through β-catenin pathway activation
PMID: 38429926
5
WNT4 contributes to cardiac fibrosis via β-catenin/NF-κB signaling
PMID: 34911029
6
Altered WNT4 expression associates with endometrial cancer
PMID: 37835474
7
WNT4 shows genetic associations across multiple female reproductive health conditions
PMID: 40069456
Disease Associationsⓘ22
mullerian aplasia and hyperandrogenismOpen Targets
0.72Strong
SERKAL syndromeOpen Targets
0.65Moderate
Mayer-Rokitansky-Küster-Hauser syndromeOpen Targets
0.47Moderate
uterine fibroidOpen Targets
0.46Moderate
endometriosisOpen Targets
0.44Moderate
Abnormality of the skeletal systemOpen Targets
0.42Moderate
pelvic organ prolapseOpen Targets
0.40Moderate
colorectal cancerOpen Targets
0.40Moderate
Mayer-Rokitansky-Küster-Hauser syndrome type 2Open Targets
0.37Weak
MURCS associationOpen Targets
0.37Weak
prolapse of female genital organOpen Targets
0.29Weak
parasitic infectionOpen Targets
0.29Weak
diverticular diseaseOpen Targets
0.28Weak
squamous cell lung carcinomaOpen Targets
0.27Weak
Left bundle branch blockOpen Targets
0.26Weak
osteoporosisOpen Targets
0.25Weak
intelligenceOpen Targets
0.22Weak
female infertilityOpen Targets
0.22Weak
carpal tunnel syndromeOpen Targets
0.19Weak
smoking cessationOpen Targets
0.19Weak
46,XX sex reversal with dysgenesis of kidneys, adrenals, and lungsUniProt
Mullerian aplasia and hyperandrogenismUniProt
Pathogenic Variants5
NM_030761.5(WNT4):c.872C>G (p.Thr291Arg)Pathogenic
SERKAL syndrome
☆☆☆☆2025→ Residue 291
NM_030761.5(WNT4):c.35T>C (p.Leu12Pro)Pathogenic
Mullerian aplasia and hyperandrogenism
☆☆☆☆2008→ Residue 12
NM_030761.5(WNT4):c.341C>T (p.Ala114Val)Pathogenic
SERKAL syndrome
☆☆☆☆2008→ Residue 114
NM_030761.5(WNT4):c.247C>T (p.Arg83Trp)Pathogenic
Mullerian aplasia and hyperandrogenism
☆☆☆☆2007→ Residue 83
NM_030761.5(WNT4):c.647A>G (p.Glu216Gly)Pathogenic
Mullerian aplasia and hyperandrogenism
☆☆☆☆2004→ Residue 216
View on ClinVar ↗
Related Genes
VANGL2Protein interaction99%DVL1Protein interaction99%DVL3Protein interaction99%PORCNProtein interaction95%LRP5Protein interaction95%RYKProtein interaction95%
Tissue Expression6 tissues
Ovary
100%
Brain
14%
Liver
5%
Lung
4%
Bone Marrow
2%
Heart
1%
Gene Interaction Network
Click a node to explore
WNT4VANGL2DVL1DVL3PORCNLRP5RYK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P56705
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.69LoF Tolerant
pLIⓘ
0.05Tolerant
Observed/Expected LoF0.46 [0.31–0.69]
RankingsWhere WNT4 stands among ~20K protein-coding genes
  • #3,779of 20,598
    Most Researched125 · top quartile
  • #3,511of 5,498
    Most Pathogenic Variants5
  • #5,251of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedWNT4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Immune-evasive human islet-like organoids ameliorate diabetes.
PMID: 32814902
Nature · 2020
1.00
2
Roles and action mechanisms of WNT4 in cell differentiation and human diseases: a review.
PMID: 34642299
Cell Death Discov · 2021
0.90
3
Nr4a1 enhances Wnt4 transcription to promote mesenchymal stem cell osteogenesis and alleviates inflammation-inhibited bone regeneration.
PMID: 38429926
Mol Ther · 2024
0.80
4
WNT4 and sex development.
PMID: 18987495
Sex Dev · 2008
0.70
5
Nephron induction.
PMID: 12386301
Nephrol Dial Transplant · 2002
0.60