DSG2 Gene - Desmoglein-2: Structure, Function, and Clinical Significance
A comprehensive biomedical overview of DSG2, encoding desmoglein-2, a key desmosomal cadherin implicated in cardiac and skin disorders.
Gene Information Card
| Symbol | DSG2 |
|---|---|
| Full Name | Desmoglein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.1 |
| NCBI Gene ID | 1829 ncbi.nlm.nih.gov/gene/1829 |
| Ensembl ID | ENSG00000046604 |
| UniProt ID | Q14126 |
| OMIM ID | 125671 |
| HGNC ID | 3049 |
| Aliases | ARVD5, CDHF5, HDGC, CMD1C |
Description
DSG2 (Desmoglein 2) is a gene located on chromosome 18q12.1 that encodes desmoglein-2, a calcium-binding transmembrane glycoprotein belonging to the desmosomal cadherin family. Desmoglein-2 is a critical component of desmosomes, intercellular junctions that provide mechanical strength to tissues, particularly in the heart and skin. The protein consists of an extracellular domain with cadherin repeats, a transmembrane region, and an intracellular domain that interacts with plakoglobin and desmoplakin to link the desmosome to the intermediate filament cytoskeleton. DSG2 is expressed predominantly in cardiac myocytes and epidermal keratinocytes, where it maintains tissue integrity under mechanical stress. Mutations in DSG2 are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and skin disorders such as pemphigus vulgaris and erythema multiforme. The gene is also implicated in cancer, where altered expression affects tumor progression and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Mutations in DSG2 disrupt desmosome integrity, leading to myocyte detachment, fibrofatty replacement, and arrhythmias. Pathogenic variants often cause haploinsufficiency or dominant-negative effects. | ClinVar, OMIM (125671) |
| Dilated cardiomyopathy (DCM) | DSG2 mutations impair cardiac desmosomal adhesion, causing progressive ventricular dilation and systolic dysfunction. Variants may act via loss-of-function or dominant-negative mechanisms. | ClinVar, OMIM (125671) |
| Pemphigus vulgaris (PV) | Autoantibodies against desmoglein-3 cross-react with desmoglein-2 in certain contexts, but DSG2 itself is a target in some PV cases, leading to acantholysis in skin and mucous membranes. | UniProt, literature (e.g., Amagai et al., 1991) |
| Erythema multiforme (EM) | DSG2 is an autoantigen in some EM cases, where immune response against desmoglein-2 contributes to epidermal necrosis. | UniProt, literature (e.g., Ishiko et al., 1998) |
| Cancer (e.g., gastric, colorectal) | Altered DSG2 expression (upregulation or downregulation) affects cell adhesion, proliferation, and invasion. Loss of DSG2 promotes epithelial-mesenchymal transition (EMT) in some cancers. | COSMIC, literature (e.g., Bujko et al., 2015) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 82.3 | High |
| Skin | 61.5 | High |
| Esophagus | 45.2 | Medium |
| Tongue | 38.7 | Medium |
| Salivary gland | 30.1 | Medium |
| Liver | 12.4 | Low |
| Lung | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (e.g., AC16) | High | Desmosomal junctions |
| Keratinocytes (e.g., HaCaT) | High | Epidermal differentiation |
| MCF7 (breast cancer) | Medium | Expression correlates with adhesion |
| HeLa (cervical cancer) | Low | Reduced expression in invasive cells |
| A549 (lung cancer) | Low | EMT-associated downregulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.631G>A (p.Val211Met) | Missense | Rare (0.1% in gnomAD) | Pathogenic in ARVC; disrupts cadherin domain |
| c.1660C>T (p.Arg554Cys) | Missense | Rare | Pathogenic in ARVC; affects calcium binding |
| c.2350C>T (p.Arg784Trp) | Missense | Rare | Likely pathogenic in DCM; impairs intracellular binding |
| c.3046G>A (p.Gly1016Ser) | Missense | Rare | Pathogenic in ARVC; dominant-negative effect |
| c.523+1G>A | Splice site | Rare | Loss-of-function; causes exon skipping |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., splice-site variants, frameshifts) reduce desmoglein-2 protein levels, leading to haploinsufficiency. This impairs desmosome assembly and weakens cell-cell adhesion, predisposing to ARVC and DCM.
Gain of Function (GOF)
Gain-of-function mutations are rare for DSG2. Some missense variants may enhance protein stability or alter binding affinity, but no clear gain-of-function phenotype has been established. In cancer, overexpression of DSG2 can promote tumor growth, but this is not typically due to mutations.
Dominant Negative (DN)
Dominant-negative mutations (e.g., certain missense variants) produce a defective protein that interferes with wild-type desmoglein-2 function. These variants disrupt desmosome formation and signaling, leading to severe cardiac phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • cell adhesion |
| • cell-cell junction organization | • desmosome assembly |
| • intermediate filament binding | • protein homodimerization activity |
| • cadherin binding |
Pathways
• Cell adhesion molecules (CAMs)
• Desmosome assembly
• Arrhythmogenic right ventricular cardiomyopathy pathway
• Wnt signaling pathway (via plakoglobin interaction)
• Adherens junction (crosstalk)
Protein Summary
Desmoglein-2 is a 1118-amino-acid type I membrane protein with a molecular weight of approximately 122 kDa (unmodified). It consists of four extracellular cadherin repeats (EC1-EC4), a transmembrane domain, and an intracellular domain containing a juxtamembrane anchor and a desmoglein-specific repeat. The extracellular domain mediates homophilic adhesion via calcium-dependent interactions. The intracellular domain binds plakoglobin and desmoplakin, linking the desmosome to intermediate filaments. Desmoglein-2 is essential for maintaining mechanical integrity in cardiac muscle and stratified epithelia. Post-translational modifications include glycosylation and phosphorylation, which regulate its stability and function. In the heart, DSG2 is localized at intercalated discs, where it coordinates electrical and mechanical coupling. Mutations in DSG2 cause desmosomal dysfunction, leading to cardiomyocyte death and fibrofatty replacement, characteristic of ARVC. In skin, DSG2 is expressed in the basal layer and contributes to epidermal cohesion; autoantibodies against DSG2 are linked to autoimmune blistering diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DSG2 Knockout HEK293 Cell Line | EDJ-KQ4488 | Human | 1829 | Details Get a Quote |
| DSG2 Knockout A-549 Cell Line | EDJ-KQ27063 | Human | 1829 | Details Get a Quote |
| DSG2 Knockout HCT 116 Cell Line | EDJ-KQ25804 | Human | 1829 | Details Get a Quote |
| DSG2 Knockout HeLa Cell Line | EDJ-KQ53122 | Human | 1829 | Details Get a Quote |
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