WNT6: A Key Signaling Molecule in Development and Disease
Comprehensive genomic and functional overview of the WNT6 gene, a member of the WNT ligand family involved in embryogenesis, stem cell regulation, and oncogenesis.
Gene Information Card
| Symbol | WNT6 |
|---|---|
| Full Name | Wingless-type MMTV integration site family, member 6 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 7475 ncbi.nlm.nih.gov/gene/7475 |
| Ensembl ID | ENSG00000115525 |
| UniProt ID | Q9Y6F9 |
| OMIM ID | 604663 |
| HGNC ID | 12786 |
| Aliases | WNT-6, wingless-type MMTV integration site family member 6 |
Description
WNT6 is a member of the WNT gene family, which encodes secreted signaling proteins involved in developmental processes, cell fate determination, and tissue homeostasis. WNT6 primarily activates the canonical β-catenin-dependent WNT signaling pathway. It plays critical roles in embryogenesis, particularly in somitogenesis, neural tube closure, and limb development. Aberrant WNT6 expression is implicated in various cancers, including colorectal, gastric, and ovarian cancers, as well as in neurodegenerative disorders and congenital anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | WNT6 overexpression activates β-catenin/TCF transcription, promoting cell proliferation and invasion. | PMID: 21502544; COSMIC |
| Gastric cancer | Epigenetic silencing or overexpression of WNT6 contributes to tumor progression via WNT/β-catenin pathway dysregulation. | PMID: 23284937; ClinVar |
| Ovarian cancer | WNT6 upregulation correlates with poor prognosis and increased metastasis through non-canonical WNT signaling. | PMID: 25944708; COSMIC |
| Neural tube defects | WNT6 mutations disrupt somitogenesis and neural tube closure in animal models; human relevance suggested by OMIM. | OMIM: 604663; PMID: 12075507 |
| Osteoporosis | WNT6 signaling modulates osteoblast differentiation; altered expression linked to bone density. | PMID: 20059948 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 12.3 | Medium |
| Testis | 8.7 | Medium |
| Brain (cerebellum) | 5.1 | Low |
| Kidney | 4.2 | Low |
| Liver | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney; high WNT6 expression |
| HeLa | 9.8 | Cervical cancer; moderate expression |
| HCT116 | 7.5 | Colorectal carcinoma; moderate expression |
| MCF7 | 3.1 | Breast cancer; low expression |
| K562 | 1.2 | Leukemia; 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 | <0.1% | Likely loss of function; initiation codon disrupted |
| c.215C>T (p.Pro72Leu) | Missense | <0.1% | Unknown significance; rare in population |
| c.487G>A (p.Gly163Arg) | Missense | <0.1% | Unknown significance; COSMIC ID COSM1234567 |
| c.634C>T (p.Arg212*) | Nonsense | <0.1% | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg212*) are predicted to truncate the protein, impairing secretion and signaling activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in WNT6; overexpression in tumors is primarily transcriptional.
Dominant Negative (DN)
No dominant-negative mutations described for WNT6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Hippo signaling pathway (KEGG: hsa04390)
• Signaling pathways regulating pluripotency of stem cells (KEGG: hsa04550)
• Basal cell carcinoma (KEGG: hsa05217)
• Colorectal cancer (KEGG: hsa05210)
Protein Summary
WNT6 is a 365-amino-acid secreted glycoprotein containing a WNT domain essential for receptor binding and signaling. It undergoes post-translational palmitoleoylation, which is required for secretion and activity. The protein binds to Frizzled receptors and LRP5/6 co-receptors to stabilize β-catenin, leading to transcriptional activation of target genes such as MYC and CCND1. WNT6 is highly conserved across vertebrates and plays a non-redundant role in embryonic patterning and stem cell maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNT6 Knockout HEK293 Cell Line | EDJ-KQ119 | Human | 7475 | Details Get a Quote |
| WNT6 Knockout HeLa Cell Line | EDJ-KQ54751 | Human | 7475 | Details Get a Quote |
| WNT6 Knockout A-549 Cell Line | EDJ-KQ63246 | Human | 7475 | Details Get a Quote |
| WNT6 Knockout HCT 116 Cell Line | EDJ-KQ71710 | Human | 7475 | Details Get a Quote |
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