WNT5A Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the WNT5A gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | WNT5A |
|---|---|
| Full Name | Wnt family member 5A |
| Gene Type | protein-coding |
| Chromosomal Location | 3p14.3 |
| NCBI Gene ID | 7474 ncbi.nlm.nih.gov/gene/7474 |
| Ensembl ID | ENSG00000114251 |
| UniProt ID | P41221 |
| OMIM ID | 164975 |
| HGNC ID | 12784 |
| Aliases | hWNT5A; Wnt-5a; protein Wnt-5a |
Description
WNT5A (Wnt family member 5A) is a secreted signaling protein that plays a critical role in embryonic development, cell polarity, and cell migration. It is a ligand for the Wnt signaling pathway, activating non-canonical pathways such as the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. WNT5A is involved in various cellular processes including proliferation, differentiation, and apoptosis. Dysregulation of WNT5A has been implicated in multiple cancers, inflammatory diseases, and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Robinow syndrome, autosomal dominant | Heterozygous mutations in WNT5A disrupt ligand-receptor interactions, impairing non-canonical Wnt signaling during skeletal development. | OMIM: 180700; ClinVar |
| Breast cancer | WNT5A expression is often reduced in aggressive breast tumors, leading to increased cell migration and invasion via altered non-canonical signaling. | COSMIC; PubMed |
| Melanoma | WNT5A promotes metastasis through activation of the PCP pathway, enhancing cell motility and invasion. | COSMIC; PubMed |
| Gastric cancer | WNT5A overexpression correlates with poor prognosis and promotes epithelial-mesenchymal transition (EMT). | COSMIC; PubMed |
| Osteoarthritis | WNT5A is upregulated in osteoarthritic cartilage and contributes to cartilage degradation via non-canonical signaling. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.8 | Medium |
| Spleen | 10.5 | Medium |
| Adipose tissue | 9.2 | Low |
| Breast | 8.1 | Low |
| Brain | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | Moderate expression |
| A549 (lung cancer) | 12.1 | Moderate expression |
| HepG2 (liver cancer) | 8.7 | Low expression |
| K562 (leukemia) | 5.2 | Low expression |
| SH-SY5Y (neuroblastoma) | 20.4 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.346C>T (p.Arg116Cys) | Missense | Rare | Impairs WNT5A secretion and signaling; associated with Robinow syndrome. |
| c.548G>A (p.Arg183His) | Missense | Rare | Disrupts receptor binding; linked to Robinow syndrome. |
| c.739G>A (p.Gly247Ser) | Missense | Somatic | Found in melanoma; may alter signaling activity. |
| c.1121C>T (p.Pro374Leu) | Missense | Somatic | Observed in gastric cancer; potential gain-of-function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in WNT5A, such as those causing Robinow syndrome, lead to reduced or absent protein activity, impairing non-canonical Wnt signaling and resulting in skeletal abnormalities.
Gain of Function (GOF)
Gain-of-function mutations, though less common, can enhance WNT5A signaling, promoting tumor progression and metastasis in cancers like melanoma and gastric cancer.
Dominant Negative (DN)
Dominant-negative mutations in WNT5A can interfere with wild-type protein function, disrupting ligand-receptor interactions and downstream signaling, as observed in some developmental disorders.
View complete mutation data：
Gene Ontology (GO)
| • Wnt-protein binding | • Wnt signaling pathway |
| • Cell-cell signaling | • Cell migration |
| • Cell polarity | • Embryonic morphogenesis |
| • Regulation of cell proliferation | • Positive regulation of cell migration |
| • Extracellular space |
Pathways
• Non-canonical Wnt signaling pathway
• Planar cell polarity pathway
• Wnt/Ca2+ pathway
• Signaling by WNT5A
Protein Summary
The WNT5A protein is a secreted glycoprotein of approximately 38-42 kDa, composed of 380 amino acids. It contains a signal peptide, a conserved Wnt domain, and multiple glycosylation sites. WNT5A binds to various receptors including Frizzled (FZD) and ROR1/ROR2, activating non-canonical signaling cascades. It plays a pivotal role in developmental processes and tissue homeostasis. Aberrant WNT5A expression or mutations contribute to oncogenesis and congenital disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNT5A Knockout HEK293 Cell Line | EDJ-KQ354 | Human | 7474 | Details Get a Quote |
| WNT5A Knockout HeLa Cell Line | EDJ-KQ18538 | Human | 7474 | Details Get a Quote |
| WNT5A Knockout A-549 Cell Line | EDJ-KQ63245 | Human | 7474 | Details Get a Quote |
| WNT5A Knockout HCT 116 Cell Line | EDJ-KQ71709 | Human | 7474 | Details Get a Quote |
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