CDX2: A Master Regulator of Intestinal Development and Homeostasis
Comprehensive genomic and clinical overview of the CDX2 gene, its role in intestinal differentiation, and its implications in colorectal cancer and other gastrointestinal disorders.
Gene Information Card
| Symbol | CDX2 |
|---|---|
| Full Name | caudal type homeobox 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.2 |
| NCBI Gene ID | 1045 ncbi.nlm.nih.gov/gene/1045 |
| Ensembl ID | ENSG00000165556 |
| UniProt ID | Q99626 |
| OMIM ID | 600297 |
| HGNC ID | 1806 |
| Aliases | CDX-3, CDX2/AS, CDX2A, CDX2B |
Description
CDX2 (caudal type homeobox 2) is a homeobox transcription factor that plays a critical role in the development and maintenance of the intestinal epithelium. It regulates the expression of genes involved in cell proliferation, differentiation, and adhesion. CDX2 is essential for establishing the intestinal phenotype and is frequently downregulated in colorectal cancer, where its loss correlates with poor prognosis and aggressive tumor behavior.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Loss of CDX2 expression leads to dedifferentiation and increased metastatic potential. CDX2 acts as a tumor suppressor by promoting intestinal differentiation and inhibiting epithelial-mesenchymal transition (EMT). | Multiple studies (e.g., Dalerba et al., 2016, Nat Med) show CDX2 loss is a marker of poor prognosis in stage II/III colorectal cancer. |
| Barrett Esophagus | Ectopic expression of CDX2 in esophageal epithelium induces intestinal metaplasia, a precursor to esophageal adenocarcinoma. | Evidence from lineage tracing and transgenic mouse models (e.g., Silberg et al., 2002, Gastroenterology). |
| Gastric Intestinal Metaplasia | Aberrant CDX2 expression in gastric mucosa drives transdifferentiation to intestinal-type epithelium, increasing gastric cancer risk. | Clinical and experimental data (e.g., Barros et al., 2012, J Pathol). |
| Congenital Sucrase-Isomaltase Deficiency | CDX2 regulates the expression of sucrase-isomaltase; mutations in CDX2 binding sites may contribute to enzyme deficiency. | Reported in rare cases (e.g., Nichols et al., 2003, Hum Mol Genet). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 78.5 | High |
| Small Intestine | 65.2 | High |
| Appendix | 52.1 | High |
| Duodenum | 48.9 | High |
| Rectum | 42.3 | High |
| Stomach | 2.1 | Low |
| Esophagus | 0.5 | Not detected |
| Pancreas | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 85.2 | Colorectal adenocarcinoma cell line; high CDX2 expression |
| HT-29 | 72.1 | Colorectal adenocarcinoma cell line; moderate expression |
| SW480 | 45.6 | Colorectal adenocarcinoma cell line; reduced expression |
| HCT116 | 38.4 | Colorectal carcinoma cell line; variable expression |
| LoVo | 30.2 | Colorectal adenocarcinoma cell line; low expression |
| MCF7 | 0.8 | Breast cancer cell line; no significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.404G>A (p.Arg135Gln) | Missense | <1% | Reduced DNA-binding affinity and transcriptional activity; reported in colorectal cancer |
| c.481C>T (p.Arg161Trp) | Missense | <1% | Impaired nuclear localization and transactivation; associated with intestinal metaplasia |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Loss of protein expression; rare in colorectal cancer |
| c.682_683del (p.Glu228fs) | Frameshift | <0.1% | Truncated protein; loss of function |
| c.1000C>T (p.Gln334*) | Nonsense | <0.1% | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CDX2 mutations (missense, nonsense, frameshift) result in loss of DNA binding, nuclear localization, or transcriptional activation, leading to reduced intestinal differentiation and tumor suppression.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CDX2. Ectopic expression in non-intestinal tissues (e.g., Barrett esophagus) is considered an oncogenic event but is not due to mutation.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg135Gln) may act in a dominant-negative manner by dimerizing with wild-type CDX2 and inhibiting its function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Intestinal epithelial cell differentiation (KEGG: hsa04974)
• Transcriptional regulation by CDX2 (Reactome: R-HSA-8866907)
• Gastric cancer (KEGG: hsa05226)
• Colorectal cancer (KEGG: hsa05210)
Protein Summary
CDX2 is a 311-amino acid homeobox transcription factor (UniProt Q99626) that contains a conserved homeodomain responsible for DNA binding. It localizes to the nucleus and regulates target genes involved in intestinal development, such as sucrase-isomaltase, MUC2, and LPH. CDX2 protein expression is a well-established immunohistochemical marker for intestinal differentiation in clinical pathology, particularly in distinguishing colorectal adenocarcinoma from other carcinomas.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDX2 Knockout HEK293 Cell Line | EDJ-KQ3954 | Human | 1045 | Details Get a Quote |
| CDX2 Knockout HCT 116 Cell Line | EDJ-KQ26223 | Human | 1045 | Details Get a Quote |
| CDX2 Knockout HeLa Cell Line | EDJ-KQ26224 | Human | 1045 | Details Get a Quote |
| CDX2 Knockout A-549 Cell Line | EDJ-KQ61341 | Human | 1045 | Details Get a Quote |
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