DSG1
Basic information
Region (hg38): 18:31318160-31359246
Previous symbols: [ "DSG" ]
Links
Phenotypes
GenCC
Source:
- palmoplantar keratoderma i, striate, focal, or diffuse (Strong), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Strong), mode of inheritance: AR
- palmoplantar keratoderma i, striate, focal, or diffuse (Strong), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Strong), mode of inheritance: AR
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Definitive), mode of inheritance: AD
- palmoplantar keratoderma i, striate, focal, or diffuse (Moderate), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Moderate), mode of inheritance: AR
- striate palmoplantar keratoderma (Supportive), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Supportive), mode of inheritance: AR
- diffuse palmoplantar keratoderma with painful fissures (Supportive), mode of inheritance: AD
- focal palmoplantar keratoderma with joint keratoses (Supportive), mode of inheritance: AD
- severe dermatitis-multiple allergies-metabolic wasting syndrome (Strong), mode of inheritance: AR
- palmoplantar keratoderma i, striate, focal, or diffuse (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM syndrome) | AR | Allergy/Immunology/Infectious | Among manifestations affecting multiple organ systems, the condition may include susceptibility to frequent and severe infections, and prophylactic measures and early and aggressive treatment of infections may be beneficial | Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Neurologic | 7544663; 10332028; 11313759; 16484817; 17194569; 19018793; 19157795; 19558595; 20082890; 23974871 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (750 variants)
- Inborn_genetic_diseases (131 variants)
- DSG1-related_disorder (35 variants)
- Palmoplantar_keratoderma_i,_striate,_focal,_or_diffuse (23 variants)
- Severe_dermatitis-multiple_allergies-metabolic_wasting_syndrome (17 variants)
- not_specified (3 variants)
- Hereditary_palmoplantar_keratoderma (2 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- Bicuspid_aortic_valve (1 variants)
- Epidermal_disease (1 variants)
- Abnormality_of_the_skin (1 variants)
- Diffuse_palmoplantar_hyperkeratosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSG1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001942.4. 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 | 162 | 11 | 179 | |||
missense | 453 | 25 | 488 | |||
nonsense | 13 | 20 | ||||
start loss | 0 | |||||
frameshift | 13 | 17 | ||||
splice donor/acceptor (+/-2bp) | 5 | |||||
Total | 28 | 11 | 463 | 187 | 20 |
Highest pathogenic variant AF is 0.00000958123
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
DSG1 | protein_coding | protein_coding | ENST00000257192 | 15 | 38941 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.927 | 0.0731 | 125730 | 0 | 18 | 125748 | 0.0000716 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.341 | 592 | 569 | 1.04 | 0.0000299 | 6863 |
Missense in Polyphen | 193 | 202.93 | 0.95106 | 2464 | ||
Synonymous | -1.40 | 227 | 202 | 1.13 | 0.0000118 | 2080 |
Loss of Function | 5.00 | 8 | 43.6 | 0.183 | 0.00000245 | 536 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000308 | 0.000308 |
Ashkenazi Jewish | 0.0000995 | 0.0000992 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000706 | 0.0000703 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.0000653 | 0.0000653 |
Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.;
- Disease
- DISEASE: Palmoplantar keratoderma 1, striate, focal, or diffuse (PPKS1) [MIM:148700]: A dermatological disorder characterized by thickening of the skin on the palms and soles, and longitudinal hyperkeratotic lesions on the palms, running the length of each finger. {ECO:0000269|PubMed:10332028}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE (EPKHE) [MIM:615508]: A syndrome characterized by severe dermatitis, multiple allergies and metabolic wasting. Clinical features include erythroderma, yellowish papules and plaques arranged at the periphery of the palms, along the fingers and over weight-bearing areas of the feet, skin erosions and scaling, and hypotrichosis. Additionally, patients manifest severe food allergies, elevated immunoglobulin E (IgE) levels and recurrent infections with marked metabolic wasting. {ECO:0000269|PubMed:23974871}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Staphylococcus aureus infection - Homo sapiens (human);Keratinization;Developmental Biology;Neutrophil degranulation;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Programmed Cell Death;Formation of the cornified envelope
(Consensus)
Recessive Scores
- pRec
- 0.210
Intolerance Scores
- loftool
- 0.361
- rvis_EVS
- 1.64
- rvis_percentile_EVS
- 96.1
Haploinsufficiency Scores
- pHI
- 0.783
- hipred
- N
- hipred_score
- 0.484
- ghis
- 0.444
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.281
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | High |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dsg1b
- Phenotype
- skeleton phenotype; vision/eye 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Gene ontology
- Biological process
- cell-cell junction assembly;homophilic cell adhesion via plasma membrane adhesion molecules;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;keratinization;response to progesterone;neutrophil degranulation;protein stabilization;maternal process involved in female pregnancy;cornification;cell-cell adhesion
- Cellular component
- cornified envelope;cytosol;plasma membrane;cell-cell junction;cytoplasmic side of plasma membrane;integral component of membrane;apical plasma membrane;lateral plasma membrane;desmosome;ficolin-1-rich granule membrane
- Molecular function
- calcium ion binding;protein binding;toxic substance binding;gamma-catenin binding