AXIN2 Gene
Axis Inhibition Protein 2: A Key Regulator of Wnt Signaling and Cancer Susceptibility
Gene Information Card
| Symbol | AXIN2 |
|---|---|
| Full Name | Axis Inhibition Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q24.1 |
| NCBI Gene ID | 8313 ncbi.nlm.nih.gov/gene/8313 |
| Ensembl ID | ENSG00000168646 |
| UniProt ID | Q9Y2T1 |
| OMIM ID | 604025 |
| HGNC ID | 904 |
| Aliases | AXIL, conductin, ODCRCS |
Description
AXIN2 (Axis Inhibition Protein 2) is a tumor suppressor gene that encodes a key negative regulator of the canonical Wnt signaling pathway. The protein forms part of the beta-catenin destruction complex, promoting beta-catenin phosphorylation and degradation. Loss-of-function mutations in AXIN2 lead to constitutive Wnt activation, contributing to colorectal cancer and other malignancies. Additionally, AXIN2 mutations are associated with oligodontia-colorectal cancer syndrome (ODCRCS), characterized by tooth agenesis and colorectal neoplasia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Loss-of-function mutations impair beta-catenin degradation, leading to Wnt pathway hyperactivation and tumorigenesis. | ClinVar, COSMIC |
| Oligodontia-Colorectal Cancer Syndrome (ODCRCS) | Germline mutations disrupt AXIN2 function, causing tooth agenesis and increased colorectal cancer risk. | OMIM, ClinVar |
| Hepatocellular Carcinoma | AXIN2 mutations or reduced expression contribute to beta-catenin accumulation and Wnt signaling activation. | COSMIC, NCBI |
| Breast Cancer | AXIN2 downregulation or mutation may promote Wnt-driven proliferation and metastasis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.5 | Medium |
| Small Intestine | 10.8 | Medium |
| Liver | 6.2 | Low |
| Breast | 4.1 | Low |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HCT116 (Colorectal) | 15.2 | High expression; Wnt-active line |
| HEK293 (Embryonic Kidney) | 8.7 | Moderate expression |
| MCF7 (Breast) | 5.4 | Low expression |
| HepG2 (Liver) | 7.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1994C>T (p.Pro665Leu) | Missense | 0.5% in colorectal cancer | Loss of function; reduced beta-catenin binding |
| c.1480C>T (p.Arg494*) | Nonsense | 0.2% in colorectal cancer | Truncation; complete loss of function |
| c.1966G>A (p.Gly656Arg) | Missense | 0.1% in hepatocellular carcinoma | Impaired destruction complex assembly |
| c.1261_1262del (p.Leu421fs) | Frameshift | 0.3% in ODCRCS | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most AXIN2 mutations are loss-of-function, impairing beta-catenin degradation and leading to Wnt pathway activation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in AXIN2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting destruction complex formation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Beta-catenin destruction complex (Reactome: R-HSA-4641262)
• Colorectal cancer (KEGG: hsa05210)
• Hepatocellular carcinoma (KEGG: hsa05225)
Protein Summary
AXIN2 is a 843-amino acid protein that functions as a scaffold in the beta-catenin destruction complex, interacting with APC, GSK3B, and beta-catenin. It contains a regulator of G-protein signaling (RGS) domain and a DIX domain essential for complex assembly. The protein is ubiquitously expressed, with highest levels in the colon and small intestine. Its primary role is to negatively regulate Wnt signaling by promoting beta-catenin phosphorylation and proteasomal degradation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AXIN2 Knockout HEK293 Cell Line | EDJ-KQ280 | Human | 8313 | Details Get a Quote |
| AXIN2 Knockout HeLa Cell Line | EDJ-KQ18337 | Human | 8313 | Details Get a Quote |
| AXIN2 Knockout HCT 116 Cell Line | EDJ-KQ18384 | Human | 8313 | Details Get a Quote |
| AXIN2 Knockout A-549 Cell Line | EDJ-KQ63341 | Human | 8313 | Details Get a Quote |
