DSP
desmoplakin, the group of Plakins
Basic information
Region (hg38): 6:7541326-7586717
Links
Phenotypes
GenCC
Source:
- keratosis palmoplantaris striata 2 (Strong), mode of inheritance: AD
- cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (Strong), mode of inheritance: AD
- lethal acantholytic epidermolysis bullosa (Strong), mode of inheritance: AR
- skin fragility-woolly hair-palmoplantar keratoderma syndrome (Strong), mode of inheritance: AR
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Strong), mode of inheritance: AR
- lethal acantholytic epidermolysis bullosa (Moderate), mode of inheritance: AR
- lethal acantholytic epidermolysis bullosa (Strong), mode of inheritance: AR
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- striate palmoplantar keratoderma (Supportive), mode of inheritance: AD
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Supportive), mode of inheritance: AD
- lethal acantholytic epidermolysis bullosa (Supportive), mode of inheritance: AR
- skin fragility-woolly hair-palmoplantar keratoderma syndrome (Supportive), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Supportive), mode of inheritance: AR
- skin fragility-woolly hair-palmoplantar keratoderma syndrome (Limited), mode of inheritance: AR
- keratosis palmoplantaris striata 2 (Limited), mode of inheritance: AD
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Moderate), mode of inheritance: AR
- cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (Moderate), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 8 (Definitive), mode of inheritance: AD
- arrhythmogenic right ventricular dysplasia 8 (Definitive), mode of inheritance: AR
- arrhythmogenic right ventricular dysplasia 8 (Strong), mode of inheritance: AD
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Strong), mode of inheritance: AR
- cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (Strong), mode of inheritance: AD
- lethal acantholytic epidermolysis bullosa (Strong), mode of inheritance: AR
- hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Definitive), mode of inheritance: AD
- arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Definitive), mode of inheritance: AD
- skin fragility-woolly hair-palmoplantar keratoderma syndrome (Definitive), mode of inheritance: AR
- keratosis palmoplantaris striata 2 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Arrhythmogenic right ventricular dysplasia, familial 8; Cardiomyopathy, dilated, with wooly hair and keratoderma; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis | AD/AR | Cardiovascular | Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation | Cardiovascular; Dermatologic | 9738775; 9887343; 10902626; 11063735; 12373648; 11841538; 16175511; 16628197; 20940358; 21193976; 22527912; 22795705; 22949226 |
| Homozygous/compound heterozygous variants reported as causing biventricular dilative cardiomyopathy with palmoplantar keratoderma and woolly hair (Skin fragility-woolly hair syndrome) |
ClinVar
This is a list of variants' phenotypes submitted to
- Arrhythmogenic_cardiomyopathy_with_wooly_hair_and_keratoderma (4182 variants)
- Arrhythmogenic_right_ventricular_dysplasia_8 (3652 variants)
- Cardiovascular_phenotype (1920 variants)
- Cardiomyopathy (1805 variants)
- not_provided (1023 variants)
- not_specified (486 variants)
- Lethal_acantholytic_epidermolysis_bullosa (400 variants)
- Woolly_hair-skin_fragility_syndrome (369 variants)
- Cardiomyopathy,_dilated,_with_wooly_hair,_keratoderma,_and_tooth_agenesis (294 variants)
- Keratosis_palmoplantaris_striata_2 (276 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (104 variants)
- DSP-related_disorder (100 variants)
- Primary_dilated_cardiomyopathy (67 variants)
- Primary_familial_hypertrophic_cardiomyopathy (16 variants)
- Epidermolysis_bullosa_simplex_due_to_plakophilin_deficiency (14 variants)
- Hypertrophic_cardiomyopathy (13 variants)
- Long_QT_syndrome (11 variants)
- Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (11 variants)
- Arrhythmogenic_cardiomyopathy (8 variants)
- Left_ventricular_noncompaction_cardiomyopathy (7 variants)
- Cardiac_arrhythmia (6 variants)
- Ventricular_tachycardia (6 variants)
- Dilated_cardiomyopathy_1S (4 variants)
- Cardiac_arrest (4 variants)
- Primary_familial_dilated_cardiomyopathy (3 variants)
- Arrhythmogenic_right_ventricular_dysplasia_9 (3 variants)
- Brugada_syndrome (2 variants)
- Skin_fragility_with_non-scarring_blistering (2 variants)
- Ventricular_fibrillation (2 variants)
- Right_ventricular_cardiomyopathy (2 variants)
- Sudden_unexplained_death (2 variants)
- Restrictive_cardiomyopathy (2 variants)
- Wolff-Parkinson-White_pattern (2 variants)
- Palmoplantar_blistering (2 variants)
- Myocarditis (2 variants)
- Dilated_cardiomyopathy_1A (1 variants)
- Progressive_familial_heart_block (1 variants)
- Subvalvular_aortic_stenosis (1 variants)
- Dilated_cardiomyopathy_1G (1 variants)
- Left_ventricular_hypertrophy (1 variants)
- Aortic_dilatation (1 variants)
- Brugada_syndrome_1 (1 variants)
- Catecholaminergic_polymorphic_ventricular_tachycardia_1 (1 variants)
- DSP-related_arrhythmogenic_cardiomyopathy (1 variants)
- Collapse_(finding) (1 variants)
- See_cases (1 variants)
- Familial_restrictive_cardiomyopathy (1 variants)
- Systolic_heart_failure (1 variants)
- Left_ventricular_noncompaction (1 variants)
- Non-compaction_cardiomyopathy (1 variants)
- Ventricular_arrhythmia (1 variants)
- Marfanoid_habitus_and_intellectual_disability (1 variants)
- Sudden_cardiac_death (1 variants)
- Skin_fragility-woolly_hair-palmoplantar_keratoderma_syndrome (1 variants)
- Bicuspid_aortic_valve (1 variants)
- Hemiplegia (1 variants)
- Ventricular_fibrillation,_paroxysmal_familial,_type_1 (1 variants)
- Hypertrophic_cardiomyopathy_2 (1 variants)
- Palmoplantar_keratoderma (1 variants)
- Migraine (1 variants)
- Long_QT_syndrome_1 (1 variants)
- Paroxysmal_familial_ventricular_fibrillation (1 variants)
- Global_developmental_delay (1 variants)
- Severe_dermatitis-multiple_allergies-metabolic_wasting_syndrome (1 variants)
- DSP-related_cardiomyopathy (1 variants)
- Sudden_death (1 variants)
- Arrhythmogenic_right_ventricular_dysplasia_1 (1 variants)
- Amyloidosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004415.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 32 | 1205 | 26 | 1263 | ||
| missense | 17 | 27 | 2393 | 513 | 16 | 2966 |
| nonsense | 172 | 90 | 268 | |||
| start loss | 2 | 2 | ||||
| frameshift | 281 | 151 | 18 | 450 | ||
| splice donor/acceptor (+/-2bp) | 51 | 69 | ||||
| Total | 478 | 319 | 2458 | 1721 | 42 |
Highest pathogenic variant AF is 0.000019825633
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DSP | protein_coding | protein_coding | ENST00000379802 | 24 | 45143 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000222 | 125650 | 0 | 98 | 125748 | 0.000390 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.595 | 1446 | 1.51e+3 | 0.957 | 0.0000895 | 18987 |
| Missense in Polyphen | 626 | 709.76 | 0.88199 | 8883 | ||
| Synonymous | -0.950 | 626 | 596 | 1.05 | 0.0000362 | 5358 |
| Loss of Function | 8.61 | 24 | 130 | 0.185 | 0.00000779 | 1540 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000872 | 0.000862 |
| Ashkenazi Jewish | 0.000599 | 0.000595 |
| East Asian | 0.000599 | 0.000544 |
| Finnish | 0.000647 | 0.000647 |
| European (Non-Finnish) | 0.000417 | 0.000334 |
| Middle Eastern | 0.000599 | 0.000544 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Major high molecular weight protein of desmosomes. Involved in the organization of the desmosomal cadherin- plakoglobin complexes into discrete plasma membrane domains and in the anchoring of intermediate filaments to the desmosomes.;
- Disease
- DISEASE: Keratoderma, palmoplantar, striate 2 (SPPK2) [MIM:612908]: A dermatological disorder characterized by thickening of the skin on the palms (linear pattern) and the soles (island-like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present. {ECO:0000269|PubMed:9887343}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, with woolly hair and keratoderma (DCWHK) [MIM:605676]: An autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy. {ECO:0000269|PubMed:11063735}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 8 (ARVD8) [MIM:607450]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. {ECO:0000269|PubMed:12373648, ECO:0000269|PubMed:15941723, ECO:0000269|PubMed:20031617}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Skin fragility-woolly hair syndrome (SFWHS) [MIM:607655]: An autosomal recessive genodermatosis characterized by skin fragility with blistering, focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, and woolly hair with varying degrees of alopecia. {ECO:0000269|PubMed:11841538}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa, lethal acantholytic (EBLA) [MIM:609638]: A form of epidermolysis bullosa characterized by severe fragility of skin and mucous membranes. The phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. Typical features include universal alopecia, neonatal teeth, and nail loss. Histopathology of the skin shows suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis (DCWHKTA) [MIM:615821]: A cardiocutaneous syndrome characterized by biventricular dilated cardiomyopathy, hyperkeratosis, woolly hair, palmoplantar keratoderma, and hypo/oligodontia. {ECO:0000269|PubMed:16628197, ECO:0000269|PubMed:20940358, ECO:0000269|PubMed:22795705}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Arrhythmogenic Right Ventricular Cardiomyopathy;Lung fibrosis;EMT transition in Colorectal Cancer;Keratinization;Developmental Biology;Neutrophil degranulation;Alpha6Beta4Integrin;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Programmed Cell Death;EGFR1;Posttranslational regulation of adherens junction stability and dissassembly;Formation of the cornified envelope
(Consensus)
Recessive Scores
- pRec
- 0.370
Intolerance Scores
- loftool
- 0.0770
- rvis_EVS
- -2.23
- rvis_percentile_EVS
- 1.32
Haploinsufficiency Scores
- pHI
- 0.672
- hipred
- Y
- hipred_score
- 0.747
- ghis
- 0.586
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.943
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Dsp
- Phenotype
- digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- desmosome organization;ventricular compact myocardium morphogenesis;epidermis development;peptide cross-linking;keratinocyte differentiation;keratinization;adherens junction organization;wound healing;neutrophil degranulation;skin development;intermediate filament cytoskeleton organization;intermediate filament organization;cornification;protein localization to adherens junction;bundle of His cell-Purkinje myocyte adhesion involved in cell communication;regulation of heart rate by cardiac conduction;cell-cell adhesion;regulation of ventricular cardiac muscle cell action potential
- Cellular component
- cornified envelope;nucleus;cytoplasm;intermediate filament;plasma membrane;fascia adherens;intercalated disc;membrane;basolateral plasma membrane;desmosome;extracellular exosome;ficolin-1-rich granule membrane
- Molecular function
- RNA binding;protein kinase C binding;structural molecule activity;structural constituent of cytoskeleton;protein binding;protein binding, bridging;cell adhesion molecule binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication;scaffold protein binding