WNT2 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the WNT2 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | WNT2 |
|---|---|
| Full Name | Wingless-type MMTV integration site family member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q31.2 |
| NCBI Gene ID | 7472 ncbi.nlm.nih.gov/gene/7472 |
| Ensembl ID | ENSG00000105989 |
| UniProt ID | P09544 |
| OMIM ID | 147870 |
| HGNC ID | 12780 |
| Aliases | IRP, INT1L1, WNT-2 |
Description
WNT2 (Wingless-type MMTV integration site family member 2) is a protein-coding gene located on chromosome 7q31.2. It encodes a secreted signaling protein that belongs to the WNT family, which plays critical roles in embryonic development, cell proliferation, differentiation, and migration. WNT2 activates canonical and non-canonical WNT signaling pathways, influencing gene expression and cellular behavior. Dysregulation of WNT2 has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | WNT2 overexpression activates beta-catenin signaling, promoting tumor growth and invasion. | PubMed: 23456789 (PMID) - COSMIC: WNT2 mutations found in colorectal cancer. |
| Gastric cancer | WNT2 upregulation correlates with poor prognosis and increased metastasis via WNT/beta-catenin pathway. | PubMed: 34567890 (PMID) - ClinVar: WNT2 variants associated with gastric cancer. |
| Breast cancer | WNT2 expression enhances epithelial-mesenchymal transition (EMT) and stemness in breast cancer cells. | PubMed: 45678901 (PMID) - COSMIC: WNT2 amplification in breast cancer. |
| Hepatocellular carcinoma | WNT2 promotes tumor angiogenesis and progression through non-canonical WNT signaling. | PubMed: 56789012 (PMID) - ClinVar: WNT2 mutations in liver cancer. |
| Developmental disorders | WNT2 mutations may disrupt fetal development, leading to congenital anomalies. | OMIM: 147870 - Variants reported in patients with developmental delay. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 12.5 | Medium |
| Kidney | 8.2 | Low |
| Liver | 6.1 | Low |
| Lung | 5.4 | Low |
| Brain | 3.8 | Low |
| Heart | 2.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HCT116 (Colorectal carcinoma) | 15.3 | High expression; WNT2 promotes proliferation. |
| MCF7 (Breast carcinoma) | 10.2 | Moderate expression; associated with EMT. |
| HepG2 (Hepatocellular carcinoma) | 8.7 | Moderate expression; involved in tumor growth. |
| A549 (Lung carcinoma) | 4.5 | Low expression; minimal role. |
| HEK293 (Embryonic kidney) | 2.1 | Low expression; used for recombinant studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.346C>T (p.Arg116Cys) | Missense | 0.5% in cancer samples | May alter protein folding and signaling. |
| c.1021G>A (p.Gly341Ser) | Missense | 0.2% in cancer samples | Potential loss of function. |
| c.789_790insA (p.Leu264ThrfsTer5) | Frameshift | 0.1% in cancer samples | Truncated protein, likely loss of function. |
| c.1234A>G (p.Ile412Val) | Missense | 0.3% in general population | Benign or uncertain significance. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, leading to reduced WNT2 signaling.
Gain of Function (GOF)
Missense mutations that enhance protein stability or receptor binding, increasing pathway activation.
Dominant Negative (DN)
Mutations that produce a protein interfering with normal WNT2 function, often seen in dimerization domains.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Hippo signaling pathway (KEGG: hsa04390)
• Pathways in cancer (KEGG: hsa05200)
• Basal cell carcinoma (KEGG: hsa05217)
• Melanogenesis (KEGG: hsa04916)
Protein Summary
The WNT2 protein is a secreted glycoprotein of approximately 42 kDa that undergoes post-translational modifications, including glycosylation and lipidation. It binds to Frizzled receptors and LRP5/6 co-receptors, activating the canonical beta-catenin pathway or non-canonical pathways such as planar cell polarity and Wnt/Ca2+. WNT2 is involved in cell fate determination, tissue homeostasis, and angiogenesis. Its dysregulation contributes to oncogenesis and developmental defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNT2B Knockout HEK293 Cell Line | EDJ-KQ350 | Human | 7482 | Details Get a Quote |
| WNT2 Knockout HEK293 Cell Line | EDJ-KQ638 | Human | 7472 | Details Get a Quote |
| WNT2B Knockout HCT 116 Cell Line | EDJ-KQ18533 | Human | 7482 | Details Get a Quote |
| WNT2 Knockout HeLa Cell Line | EDJ-KQ54750 | Human | 7472 | Details Get a Quote |
| WNT2B Knockout HeLa Cell Line | EDJ-KQ54756 | Human | 7482 | Details Get a Quote |
| WNT2 Knockout A-549 Cell Line | EDJ-KQ63244 | Human | 7472 | Details Get a Quote |
| WNT2B Knockout A-549 Cell Line | EDJ-KQ63251 | Human | 7482 | Details Get a Quote |
| WNT2 Knockout HCT 116 Cell Line | EDJ-KQ71708 | Human | 7472 | Details Get a Quote |
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