DSC2 Gene: Desmocollin-2 in Cardiac Health and Disease
Essential desmosomal cadherin implicated in arrhythmogenic cardiomyopathy and cancer
Gene Information Card
| Symbol | DSC2 |
|---|---|
| Full Name | Desmocollin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.1 |
| NCBI Gene ID | 1824 ncbi.nlm.nih.gov/gene/1824 |
| Ensembl ID | ENSG00000134755 |
| UniProt ID | Q02487 |
| OMIM ID | 125645 |
| HGNC ID | 3036 |
| Aliases | ARVD11, CDHF5, DG2, DSC3 |
Description
The DSC2 gene encodes desmocollin-2, a calcium-dependent cell adhesion glycoprotein that is a major component of desmosomes. Desmosomes are intercellular junctions that provide mechanical strength to tissues, particularly the heart and skin. DSC2 is essential for maintaining myocardial integrity and electrical coupling. Mutations in DSC2 are a well-established cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), a hereditary heart muscle disease characterized by fibrofatty replacement of the myocardium and risk of sudden cardiac death. Beyond the heart, DSC2 has been implicated in cancer progression and epithelial barrier function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Loss-of-function mutations in DSC2 disrupt desmosome assembly, leading to myocyte detachment, cell death, and fibrofatty infiltration, particularly in the right ventricle. This impairs electrical conduction and predisposes to arrhythmias. | ClinVar, OMIM (ARVD11) |
| Dilated cardiomyopathy (DCM) | Some DSC2 mutations have been reported in DCM patients, suggesting a broader role in cardiac function. The mechanism likely involves impaired desmosomal integrity and altered calcium handling. | ClinVar, literature |
| Skin disorders (e.g., pemphigus-like phenotypes) | DSC2 is expressed in the epidermis; however, its role in skin disease is less defined compared to other desmocollins. Some studies suggest involvement in cell adhesion defects. | UniProt, literature |
| Cancer (e.g., colorectal, gastric, breast) | DSC2 expression is often downregulated in epithelial cancers, correlating with loss of cell adhesion and increased invasiveness. In some contexts, DSC2 may act as a tumor suppressor. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (e.g., 100+ nTPM) | High |
| Skin | High (e.g., 80-100 nTPM) | High |
| Esophagus | Moderate (e.g., 30-50 nTPM) | Medium |
| Liver | Low (e.g., <10 nTPM) | Low |
| Brain | Low (e.g., <5 nTPM) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (e.g., AC16) | High | Desmosomal component |
| Keratinocytes (e.g., HaCaT) | High | Epidermal adhesion |
| Colorectal cancer lines (e.g., Caco-2) | Moderate | Epithelial differentiation |
| HeLa (cervical) | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.631-2A>G (splice site) | Splice site | Rare | Splice disruption leading to truncated protein; associated with ARVC |
| p.Gly812Ser (missense) | Missense | Rare | Alters calcium-binding domain; impairs adhesion; ARVC |
| p.Arg48Trp (missense) | Missense | Rare | Disrupts cadherin repeat; loss of function; ARVC |
| p.Val30Met (missense) | Missense | Rare | Potential pathogenic; uncertain significance |
| p.Gln558* (nonsense) | Nonsense | Rare | Premature stop; loss of function; ARVC |
Mutation functional classification
Loss of Function (LOF)
Most DSC2 mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects that impair desmosome assembly and cell-cell adhesion.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for DSC2; the gene primarily acts as a structural protein.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by incorporating mutant protein into desmosomes, disrupting their structure and function.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • cell adhesion |
| • cell-cell junction organization | • desmosome assembly |
| • protein homodimerization activity | • cadherin binding |
Pathways
• Cell adhesion molecules (CAMs)
• Desmosome assembly
• Arrhythmogenic right ventricular cardiomyopathy (ARVC) pathway
• Wnt signaling (via beta-catenin interaction)
Protein Summary
Desmocollin-2 is a type I membrane protein belonging to the cadherin superfamily. It contains extracellular cadherin repeats that mediate calcium-dependent homophilic adhesion, a single transmembrane domain, and a cytoplasmic tail that interacts with plakoglobin and desmoplakin to link desmosomes to intermediate filaments. In the heart, DSC2 is predominantly expressed in intercalated discs, where it maintains mechanical coupling between cardiomyocytes. Alternative splicing produces multiple isoforms, with the 'a' and 'b' forms differing in cytoplasmic domain length. Post-translational modifications include glycosylation and proteolytic processing. DSC2 also plays a role in epithelial differentiation and has been implicated in tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DSC2 Knockout HEK293 Cell Line | EDJ-KQ13216 | Human | 1824 | Details Get a Quote |
| DSC2 Knockout HCT 116 Cell Line | EDJ-KQ41360 | Human | 1824 | Details Get a Quote |
| DSC2 Knockout A-549 Cell Line | EDJ-KQ42583 | Human | 1824 | Details Get a Quote |
| DSC2 Knockout HeLa Cell Line | EDJ-KQ42585 | Human | 1824 | Details Get a Quote |
| DSC2 Knockout MGC-803 Cell Line | EDJ-KZ193 | Human | 1824 | Details Get a Quote |
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