DSP
Chr 6ADARdesmoplakin
A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25733715). Critical for cell-cell adhesion in early stage blastocysts and progression through proamniotic cavity formation (By similarity). Not required for preimplantation morphogenic process in blastocysts (By similarity). Required for keratin filament anchoring at the desmosome junction and subsequent organization of the keratin intermediate filament network within the cytoplasm (By similarity). Required for anchoring of desmosomes to the microtubule architecture, via its interaction with NIN (By similarity). Plays a key role in adhesion and organization of the dermal epithelial barrier (By similarity). Critical for the maintenance of the neural tube structure following formation and organization of the neuroepithelium (By similarity). Facilitates outgrowth and repair of motor neuron fibers in regenerating axons following injury, probably by promoting recruitment of a complex containing DSP, CDH2, VIM and JUP to the outgrowth tips (By similarity). Required for the normal formation of the heart, also required for development of vascular capillary structures and intact endothelial cell barriers (By similarity). Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). Maintains cardiac rhythmicity by ensuring correct cell-cell adhesion within the sinoatrial node, via stabilization of protein components of both desmosome and Gap junctions (By similarity). Involved in maintaining the protein stability and recruitment of GJA1 to functional gap junctions, via inhibition of KRAS-mediated MAPK1/MAPK3 phosphorylation of GJA1 (By similarity). Required for the survival and maintenance of germ cells in the gonads during embryonic development (By similarity). Binds to telomere DNA (via C-terminus) and acts to prevent telomere damage and maintain telomere length via its interaction with TRF2 (PubMed:31595153)
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
2 total gene-disease associations curated
Some data sources returned errors (1)
ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
578 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 39 | 0 | 23 | 0 | 62 |
Likely Pathogenic | 13 | 1 | 6 | 0 | 20 |
VUS | 5 | 314 | 14 | 1 | 334 |
Likely Benign | 0 | 12 | 38 | 109 | 159 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 3 | |||
| Total | 57 | 327 | 81 | 110 | 578 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DSP · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
DSP-related arrhythmogenic right ventricular cardiomyopathy
definitiveDSP-related arrhythmogenic right ventricular cardiomyopathy
definitiveDSP-related hypertrophic cardiomyopathy
disputedDSP-related dilated cardiomyopathy
definitiveDSP-related palmoplantar keratoderma, striate
definitiveDSP-related developmental disorder
moderateDSP-related skin fragility, woolly hair
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
Cardiomyopathy, dilated, with woolly hair and keratoderma
MIM #605676Molecular basis of disorder known
Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis
MIM #615821Molecular basis of disorder known
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer
RECRUITINGRadiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma.
NOT YET RECRUITINGSUV PDL1/PD1 in Sun Damaged & Sun Protected Human Skin of Participants
RECRUITINGBiomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)
RECRUITINGPBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC
RECRUITINGTissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy
RECRUITINGDHF-20-1839-2: Clinical Performance Study Protocol for Therascreen® KRAS RGQ PCR Kit
RECRUITINGExternal Resources
Links to major genomics databases and tools