APC2 Gene (APC Regulator of WNT Signaling Pathway 2)
Comprehensive genomic and functional overview of APC2, a tumor suppressor gene involved in colorectal cancer and neurodevelopmental disorders.
Gene Information Card
| Symbol | APC2 |
|---|---|
| Full Name | APC regulator of WNT signaling pathway 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 10297 ncbi.nlm.nih.gov/gene/10297 |
| Ensembl ID | ENSG00000115266 |
| UniProt ID | O95996 |
| OMIM ID | 612034 |
| HGNC ID | 24036 |
| Aliases | APCL, FLJ20295, MGC119413 |
Description
APC2 (APC regulator of WNT signaling pathway 2) encodes a protein that functions as a tumor suppressor by negatively regulating the canonical WNT signaling pathway. It forms a complex with AXIN1, CTNNB1 (beta-catenin), and GSK3B to promote the phosphorylation and degradation of beta-catenin. Loss of APC2 function leads to aberrant WNT activation and is implicated in colorectal cancer, gastric cancer, and neurodevelopmental disorders such as Sotos syndrome. The gene is located on chromosome 19p13.3 and is highly expressed in brain and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of function mutations or promoter hypermethylation reduce beta-catenin degradation, activating WNT signaling. | ClinVar, COSMIC |
| Sotos syndrome 2 | Heterozygous loss-of-function mutations in APC2 cause overgrowth and intellectual disability via disrupted WNT regulation. | OMIM #617169 |
| Gastric cancer | APC2 downregulation via methylation or mutation contributes to tumor progression. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Colon | 4.1 | Medium |
| Liver | 2.0 | Low |
| Heart | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HCT116 | 6.8 | Moderate expression |
| HeLa | 4.5 | Low expression |
| MCF7 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncated protein |
| c.789_790del (p.Glu264fs) | Frameshift | <0.1% | Loss of function; premature stop |
| c.1567G>A (p.Gly523Arg) | Missense | 0.2% | Likely damaging; impaired beta-catenin binding |
| c.2101C>T (p.Arg701Trp) | Missense | 0.1% | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Most APC2 mutations are loss-of-function (nonsense, frameshift, splice site), leading to truncated or unstable protein and constitutive WNT signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for APC2.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with the wild-type protein's ability to form the destruction complex.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Colorectal cancer (KEGG: hsa05210)
• Beta-catenin destruction complex (Reactome: R-HSA-4641263)
Protein Summary
The APC2 protein (UniProt O95996) is a 2303-amino acid tumor suppressor that contains an N-terminal oligomerization domain, armadillo repeats, and multiple beta-catenin and AXIN binding sites. It localizes to the cytoplasm and plasma membrane, where it scaffolds the destruction complex to target beta-catenin for ubiquitin-mediated degradation. APC2 is structurally similar to APC but lacks the C-terminal microtubule-binding domain. Its expression is highest in brain and testis, and loss of function is oncogenic in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APC2 Knockout HEK293 Cell Line | EDJ-KQ277 | Human | 10297 | Details Get a Quote |
| APC2 Knockout HeLa Cell Line | EDJ-KQ18345 | Human | 10297 | Details Get a Quote |
| APC2 Knockout HCT 116 Cell Line | EDJ-KQ18382 | Human | 10297 | Details Get a Quote |
| APC2 Knockout A-549 Cell Line | EDJ-KQ63852 | Human | 10297 | Details Get a Quote |
