DSG4

desmoglein 4, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:31376777-31414912

Links

ENSG00000175065 ∙ NCBI:147409 ∙ OMIM:607892 ∙ HGNC:21307 ∙ Uniprot:Q86SJ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• monilethrix (Supportive), mode of inheritance: AD
• hypotrichosis simplex (Supportive), mode of inheritance: AD
• hypotrichosis 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotrichosis 6	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	12705872; 16543896; 16439973; 16575393; 17392831; 21495994

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DSG4 gene.

• Hypotrichosis 6 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSG4 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			6	20	8	34
missense			97	14	3	114
nonsense	1	1	1			3
start loss						0
frameshift		1	2			3
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)	1		1			2
splice region			2	4		6
non coding			11	2	20	33
Total	2	2	119	36	32

Highest pathogenic variant AF is 0.0000131

Variants in DSG4

This is a list of pathogenic ClinVar variants found in the DSG4 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-31376779-C-T		Hypotrichosis 6	Uncertain significance (Apr 27, 2017)
18-31376811-T-A		Hypotrichosis 6	Uncertain significance (Jan 13, 2018)
18-31376824-A-G		Hypotrichosis 6	Uncertain significance (Jan 12, 2018)
18-31376846-G-A		Hypotrichosis 6	Uncertain significance (Jan 12, 2018)
18-31376860-G-A		Hypotrichosis 6	Uncertain significance (Jan 13, 2018)
18-31376869-A-C		Hypotrichosis 6	Uncertain significance (Jan 13, 2018)
18-31376869-A-G		Hypotrichosis 6	Uncertain significance (Jan 13, 2018)
18-31376896-A-G		Hypotrichosis 6	Uncertain significance (Jan 12, 2018)
18-31376902-A-G		Hypotrichosis 6 • DSG4-related disorder	Uncertain significance (Jan 13, 2018)
18-31376929-C-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
18-31376932-A-G		Hypotrichosis 6 • DSG4-related disorder	Benign/Likely benign (Jul 28, 2023)
18-31376941-C-T		Hypotrichosis 6	Benign (Jan 29, 2024)
18-31377109-A-T			Benign (Jun 18, 2021)
18-31384897-T-C			Benign (Jun 18, 2021)
18-31385136-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
18-31385138-G-A			Likely benign (Nov 27, 2023)
18-31385161-T-C		Inborn genetic diseases	Uncertain significance (Oct 08, 2024)
18-31385169-G-T			Likely pathogenic (Oct 23, 2020)
18-31386555-G-C			Benign (Nov 11, 2018)
18-31386689-TG-T		Hypotrichosis 6	Likely pathogenic (-)
18-31386703-A-G		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
18-31386726-GCAAA-G		Hypotrichosis 6	Pathogenic (May 26, 2023)
18-31386732-A-C			Likely benign (Sep 23, 2022)
18-31386779-G-A		Hypotrichosis 6 • Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
18-31386799-A-G			Likely benign (Mar 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DSG4	protein_coding	protein_coding	ENST00000359747	15	38136

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.91e-13	0.988	125627	0	121	125748	0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.02	654	585	1.12	0.0000317	6922
Missense in Polyphen		244	214.32	1.1385		2652
Synonymous	0.618	211	223	0.947	0.0000141	2079
Loss of Function	2.53	27	45.4	0.595	0.00000231	570

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00112
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000490	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000608	0.000607
Middle Eastern	0.000490	0.000489
South Asian	0.000459	0.000457
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Coordinates the transition from proliferation to differentiation in hair follicle keratinocytes (By similarity). {ECO:0000250}.
• Disease: DISEASE: Hypotrichosis 6 (HYPT6) [MIM:607903]: A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. {ECO:0000269|PubMed:15191570}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Autoantibodies against DSG4 are found in patients with pemphigus vulgaris. Pemphigus vulgaris is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Recessive Scores

• pRec: 0.166

Intolerance Scores

• loftool: 0.945
• rvis_EVS: 1.83
• rvis_percentile_EVS: 97.05

Haploinsufficiency Scores

• pHI: 0.306
• hipred: N
• hipred_score: 0.350

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.154

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dsg4
• Phenotype: immune system phenotype; 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); hematopoietic system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); pigmentation phenotype; homeostasis/metabolism 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: hair follicle development;homophilic cell adhesion via plasma membrane adhesion molecules;BMP signaling pathway;keratinization;cornification
• Cellular component: cornified envelope;plasma membrane;integral component of membrane;desmosome
• Molecular function: calcium ion binding