DSC2

Chr 18ADAR

desmocollin 2

Also known as: ARVD11, CDHF2, DG2, DGII/III, DSC3

NCBI Gene: 1824ENSG00000134755UniProt: Q02487

Desmocollin-2 is a cadherin-like transmembrane glycoprotein that forms desmosomes, specialized cell-cell junctions that maintain cellular adhesion and resist mechanical stress in tissues like the heart and skin. Mutations cause arrhythmogenic right ventricular dysplasia-11, a cardiomyopathy that can present with or without mild palmoplantar keratoderma and woolly hair. Inheritance follows both autosomal dominant and autosomal recessive patterns.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Arrhythmogenic right ventricular dysplasia 11MIM #610476
ADAR
Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hairMIM #610476
ADAR
1
Active trials
25
Pubs (1 yr)
20
P/LP submissions
0%
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DSC2
🧬
Gene-Disease Validity (ClinGen)
familial isolated arrhythmogenic right ventricular dysplasia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 176 VUS of 300 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — DSC2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.13
OE 0.47 (0.33–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.37Z-score
OE missense 0.95 (0.88–1.03)
458 obs / 481.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.33–0.69)
0≤0.351.4
Missense OE0.95 (0.88–1.03)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 19 / 40.5Missense obs/exp: 458 / 481.0Syn Z: -0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDSC2-related arrhythmogenic right ventricular cardiomyopathyOTHERAD
definitiveDSC2-related arrhythmogenic right ventricular cardiomyopathyOTHERAR
DN
0.78top 25%
GOF
0.76top 25%
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median
LOF1 literature citation · 56% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFGehmlich et al. (2010) used transient transfection assays to study the function and expression of missense and frameshift mutations in DSC2. The authors conclude that the missense mutations result in a decrease of available DCS2 mature functional protein, and this decrease, rather than a dominant nePMID:21062920

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic7
VUS176
Likely Benign90
Conflicting1
11
Pathogenic
7
Likely Pathogenic
176
VUS
90
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
6
0
11
Likely Pathogenic
5
0
2
0
7
VUS
10
149
15
2
176
Likely Benign
0
2
28
60
90
Benign
0
0
0
0
0
Conflicting
—1
Total201515162285

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DSC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The role of the desmosomal protein desmocollin 2 in tumour progression in triple negative breast cancer patients
Reimer F et al.·Cancer Cell Int
2023Cohort
DSC2 suppresses the growth of gastric cancer through the inhibition of nuclear translocation of gamma-catenin and PTEN/PI3K/AKT signaling pathway
Sun C et al.·Aging (Albany NY)
2023
Deciphering DSC2 arrhythmogenic cardiomyopathy electrical instability: From ion channels to ECG and tailored drug therapy
Moreau A et al.·Clin Transl Med
2021
Validation the role of desmocollin-2 in osteosarcoma based on single cell and bulk RNA seq and experimental analyses
Zeng J et al.·J Cancer
2023
Alterations in Calcium Handling Are a Common Feature in an Arrhythmogenic Cardiomyopathy Cell Model Triggered by Desmosome Genes Loss
Vallverdú-Prats M et al.·Int J Mol Sci
2023Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients