DSG1

desmoglein 1, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31318159-31359246

Previous symbols: [ "DSG" ]

Links

ENSG00000134760 ∙ NCBI:1828 ∙ OMIM:125670 ∙ HGNC:3048 ∙ Uniprot:Q02413 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• 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 (Definitive), mode of inheritance: AD
• severe dermatitis-multiple allergies-metabolic wasting syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the DSG1 gene.

• not provided (530 variants)
• Inborn genetic diseases (47 variants)
• Palmoplantar keratoderma i, striate, focal, or diffuse (10 variants)
• not specified (6 variants)
• Severe dermatitis-multiple allergies-metabolic wasting syndrome (5 variants)
• Palmoplantar keratoderma i, striate, focal, or diffuse;Severe dermatitis-multiple allergies-metabolic wasting syndrome (4 variants)
• DSG1-related condition (3 variants)
• Hereditary palmoplantar keratoderma;Diffuse palmoplantar hyperkeratosis (1 variants)
• Abnormality of the skin (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	111	11	125
missense			257	13	18	288
nonsense	8	4	1			13
start loss						0
frameshift	7	2	1			10
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region		1	7	10	1	19
non coding			1	47	43	91
Total	15	7	263	171	72

Highest pathogenic variant AF is 0.00000658

Variants in DSG1

This is a list of pathogenic ClinVar variants found in the DSG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-31318238-A-G			Benign (Nov 11, 2018)
18-31318293-C-A		DSG1-related disorder	Likely benign (Dec 09, 2019)
18-31318304-G-C			Uncertain significance (Sep 25, 2022)
18-31318309-G-C			Uncertain significance (Nov 12, 2020)
18-31318319-A-G			Uncertain significance (Jul 28, 2023)
18-31318331-A-G		not specified • Palmoplantar keratoderma i, striate, focal, or diffuse • Severe dermatitis-multiple allergies-metabolic wasting syndrome	Benign (Feb 01, 2024)
18-31318334-C-T			Likely benign (Feb 16, 2023)
18-31318340-A-G			Uncertain significance (Sep 02, 2022)
18-31318340-A-T			Benign (Jan 12, 2024)
18-31318340-A-AT			Pathogenic (Oct 16, 2021)
18-31318351-G-C			Uncertain significance (Jul 11, 2022)
18-31318355-G-A			Likely benign (Jul 29, 2023)
18-31318356-G-T			Likely benign (Apr 14, 2023)
18-31318360-C-T			Likely benign (Jul 03, 2022)
18-31318364-T-C			Likely benign (Oct 05, 2023)
18-31318367-A-C			Likely benign (Feb 16, 2023)
18-31318604-G-A			Benign (Nov 11, 2018)
18-31326497-T-C			Benign (Nov 11, 2018)
18-31326498-G-A			Benign (Nov 11, 2018)
18-31326580-G-A		Severe dermatitis-multiple allergies-metabolic wasting syndrome	Pathogenic (Oct 01, 2013)
18-31326582-T-C			Uncertain significance (Dec 29, 2022)
18-31326608-C-T		Palmoplantar keratoderma i, striate, focal, or diffuse	Likely pathogenic (May 23, 2017)
18-31326609-G-A			Uncertain significance (Feb 01, 2023)
18-31326610-A-G			Likely benign (Nov 03, 2023)
18-31326625-T-C			Likely benign (Apr 24, 2023)

GnomAD

Source: gnomAD

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: 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

	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