WNT4: A Key Regulator of Female Development and Beyond
Comprehensive genomic and functional analysis of the WNT4 gene
Gene Information Card
| Symbol | WNT4 |
|---|---|
| Full Name | Wnt family member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.12 |
| NCBI Gene ID | 54361 ncbi.nlm.nih.gov/gene/54361 |
| Ensembl ID | ENSG00000162552 |
| UniProt ID | P56705 |
| OMIM ID | 603490 |
| HGNC ID | 12783 |
| Aliases | WNT-4, wingless-type MMTV integration site family member 4 |
Description
WNT4 is a member of the WNT gene family, which encodes secreted signaling proteins involved in embryogenesis, cell fate determination, and tissue homeostasis. WNT4 plays a critical role in female reproductive tract development, kidney function, and adrenal gland regulation. It activates canonical and non-canonical Wnt signaling pathways, influencing cell proliferation, differentiation, and migration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Müllerian aplasia and hyperandrogenism (MAHA) | Loss-of-function mutations in WNT4 disrupt Müllerian duct development and ovarian steroidogenesis, leading to uterine agenesis and androgen excess. | ClinVar, OMIM |
| SERKAL syndrome | Homozygous WNT4 mutations impair Wnt signaling, causing severe renal agenesis, gonadal dysgenesis, and adrenal insufficiency. | OMIM, NCBI |
| 46,XX disorders of sex development | WNT4 deficiency leads to virilization and ovarian dysfunction due to altered Wnt/β-catenin signaling. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Ovary | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Adrenal gland | 6.1 | Low |
| Uterus | 4.7 | Low |
| Breast | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| OVCAR-3 (ovarian cancer) | 15.2 | High expression |
| HEK 293 (embryonic kidney) | 9.8 | Moderate expression |
| MCF-7 (breast cancer) | 3.4 | Low expression |
| HepG2 (liver cancer) | 1.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of function; associated with MAHA |
| c.469C>T (p.Arg157*) | Nonsense | Rare | Premature truncation; SERKAL syndrome |
| c.652G>A (p.Gly218Arg) | Missense | Rare | Impaired secretion; 46,XX DSD |
Mutation functional classification
Loss of Function (LOF)
Most WNT4 mutations are loss-of-function, reducing or abolishing protein secretion and signaling activity, leading to developmental defects.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in WNT4.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type WNT4 signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Signaling by WNT (Reactome: R-HSA-195721)
• Beta-catenin independent WNT signaling (Reactome: R-HSA-4086400)
Protein Summary
WNT4 is a secreted glycoprotein of approximately 40 kDa, belonging to the WNT family. It contains a conserved WNT domain and multiple cysteine residues essential for proper folding and signaling. WNT4 primarily signals through the non-canonical Wnt pathway (e.g., planar cell polarity and Ca2+ signaling) but can also activate canonical β-catenin-dependent transcription in specific contexts. It is critical for female reproductive tract development, kidney morphogenesis, and adrenal function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNT4 Knockout HEK293 Cell Line | EDJ-KQ353 | Human | 54361 | Details Get a Quote |
| WNT4 Knockout HeLa Cell Line | EDJ-KQ18537 | Human | 54361 | Details Get a Quote |
| WNT4 Knockout A-549 Cell Line | EDJ-KQ64903 | Human | 54361 | Details Get a Quote |
| WNT4 Knockout HCT 116 Cell Line | EDJ-KQ73347 | Human | 54361 | Details Get a Quote |
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