DSG1

desmoglein 1, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31318160-31359246

Previous symbols: [ "DSG" ]

Links

ENSG00000134760NCBI:1828OMIM:125670HGNC:3048Uniprot:Q02413AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM syndrome)ARAllergy/Immunology/InfectiousAmong 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 beneficialAllergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Neurologic7544663; 10332028; 11313759; 16484817; 17194569; 19018793; 19157795; 19558595; 20082890; 23974871

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DSG1 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
162
clinvar
11
clinvar
179
missense
1
clinvar
453
clinvar
25
clinvar
9
clinvar
488
nonsense
13
clinvar
4
clinvar
3
clinvar
20
start loss
0
frameshift
13
clinvar
3
clinvar
1
clinvar
17
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
5
Total 28 11 463 187 20

Highest pathogenic variant AF is 0.00000958123

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DSG1protein_codingprotein_codingENST00000257192 1538941
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9270.07311257300181257480.0000716
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.3415925691.040.00002996863
Missense in Polyphen193202.930.951062464
Synonymous-1.402272021.130.00001182080
Loss of Function5.00843.60.1830.00000245536

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003080.000308
Ashkenazi Jewish0.00009950.0000992
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00007060.0000703
Middle Eastern0.00005440.0000544
South Asian0.00006530.0000653
Other0.0001630.000163

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

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