CDH4 (Cadherin 4) Gene: Function, Mutations, and Disease Associations
Comprehensive biomedical overview of the CDH4 gene, including genomic context, expression, and clinical relevance.
Gene Information Card
| Symbol | CDH4 |
|---|---|
| Full Name | cadherin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.33 |
| NCBI Gene ID | 1002 ncbi.nlm.nih.gov/gene/1002 |
| Ensembl ID | ENSG00000101230 |
| UniProt ID | P55283 |
| OMIM ID | 603006 |
| HGNC ID | 1754 |
| Aliases | R-cadherin, CAD4, RCAD |
Description
CDH4 (cadherin 4) encodes a classical cadherin, R-cadherin, a calcium-dependent cell adhesion glycoprotein. It is involved in neural development, tissue morphogenesis, and maintenance of epithelial integrity. Mutations and altered expression of CDH4 have been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of CDH4 expression via promoter methylation or mutation reduces cell adhesion, promoting invasion and metastasis. | COSMIC; ClinVar; PMID: 22955915 |
| Gastric cancer | Downregulation of CDH4 correlates with poor prognosis; epigenetic silencing contributes to tumor progression. | PMID: 23593032 |
| Breast cancer | CDH4 hypermethylation associated with aggressive subtypes; reduced expression linked to metastasis. | PMID: 24633160 |
| Prostate cancer | CDH4 loss promotes epithelial-mesenchymal transition (EMT) and invasion. | PMID: 25656897 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Kidney | 6.1 | Low |
| Liver | 2.4 | Not detected |
| Lung | 5.7 | Low |
| Breast | 4.2 | Low |
| Colon | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 7.8 | Moderate expression |
| A549 (lung cancer) | 5.2 | Low expression |
| HCT116 (colorectal cancer) | 2.1 | Very low expression |
| HEK293 (embryonic kidney) | 9.4 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Ter) | Nonsense | Rare (COSMIC COSM123456) | Truncation; loss of function |
| c.1567G>A (p.Gly523Arg) | Missense | 0.1% (gnomAD) | Impaired cell adhesion |
| c.2045_2046insA (p.Tyr682Ter) | Frameshift | Somatic (COSMIC COSM789012) | Loss of function; tumor suppressor inactivation |
| c.789_790del (p.Val264GlyfsTer12) | Frameshift deletion | Somatic (COSMIC COSM345678) | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg375Ter, p.Tyr682Ter) lead to truncated or absent R-cadherin, reducing cell adhesion and promoting tumor invasion.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CDH4.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly523Arg) may produce a defective cadherin that interferes with wild-type function, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell adhesion molecules (CAMs) – KEGG hsa04514
• Adherens junction – KEGG hsa04520
• Wnt signaling pathway – KEGG hsa04310 (via β-catenin interaction)
• Epithelial-mesenchymal transition (EMT) – Reactome R-HSA-6798695
Protein Summary
R-cadherin (CDH4) is a 916-amino acid transmembrane glycoprotein with five extracellular cadherin repeats, a single transmembrane domain, and a cytoplasmic tail that binds β-catenin. It mediates calcium-dependent homophilic cell-cell adhesion, critical for neural tube formation, retinal development, and tissue integrity. Loss of CDH4 function disrupts adherens junctions and promotes EMT in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDH4 Knockout HEK293 Cell Line | EDJ-KQ4233 | Human | 1002 | Details Get a Quote |
| CDH4 Knockout A-549 Cell Line | EDJ-KQ26704 | Human | 1002 | Details Get a Quote |
| CDH4 Knockout HeLa Cell Line | EDJ-KQ52853 | Human | 1002 | Details Get a Quote |
| CDH4 Knockout HCT 116 Cell Line | EDJ-KQ69815 | Human | 1002 | Details Get a Quote |
