DSC3

desmocollin 3, the group of Desmosomal cadherins

Basic information

Region (hg38): 18:30989364-31042815

Previous symbols: [ "DSC4" ]

Links

ENSG00000134762 ∙ NCBI:1825 ∙ OMIM:600271 ∙ HGNC:3037 ∙ Uniprot:Q14574 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary hypotrichosis with recurrent skin vesicles (Moderate), mode of inheritance: AR
• hereditary hypotrichosis with recurrent skin vesicles (Strong), mode of inheritance: AR
• hereditary hypotrichosis with recurrent skin vesicles (Moderate), mode of inheritance: AR
• hereditary hypotrichosis with recurrent skin vesicles (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotrichosis and recurrent skin vesicles	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	19765682

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DSC3 gene.

• not provided (57 variants)
• Inborn genetic diseases (30 variants)
• not specified (1 variants)
• Hereditary hypotrichosis with recurrent skin vesicles (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSC3 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	3
missense			26	2	5	33
nonsense		1				1
start loss						0
frameshift	1			1		2
inframe indel						0
splice donor/acceptor (+/-2bp)		2			1	3
splice region						0
non coding			2		42	44
Total	1	3	28	3	51

Highest pathogenic variant AF is 0.000295

Variants in DSC3

This is a list of pathogenic ClinVar variants found in the DSC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-30993914-T-TA			Benign (Jun 20, 2021)
18-30993914-T-TAA			Benign (Jun 19, 2021)
18-30994031-T-C			Benign (Jun 19, 2021)
18-30994480-T-G		not specified	Uncertain significance (Jul 14, 2021)
18-30994486-C-G		not specified	Uncertain significance (Feb 13, 2023)
18-30994506-G-A		DSC3-related disorder	Benign (Nov 04, 2019)
18-30994547-AG-A			Benign (Jun 20, 2021)
18-30994591-T-G			Benign (Jun 20, 2021)
18-30996567-A-C			Benign (Nov 11, 2018)
18-30996790-C-T			Uncertain significance (-)
18-30996796-C-T			Likely benign (May 16, 2018)
18-30996827-C-T			Benign (Nov 11, 2018)
18-30996882-A-C		not specified	Uncertain significance (May 31, 2023)
18-30996900-G-GC			Likely benign (Jul 20, 2018)
18-30996906-C-A		not specified	Uncertain significance (Oct 30, 2023)
18-30997049-C-A			Likely pathogenic (Jun 28, 2022)
18-30997050-T-C			Likely pathogenic (Jun 28, 2022)
18-30997313-C-G			Benign (Nov 12, 2018)
18-30997349-C-A			Benign (Nov 11, 2018)
18-31001476-T-C			Benign (Nov 11, 2018)
18-31001625-T-A		not specified	Uncertain significance (Jan 16, 2024)
18-31001626-C-T		not specified	Uncertain significance (May 13, 2022)
18-31001635-G-A		DSC3-related disorder	Likely benign (Aug 16, 2019)
18-31001673-A-C		Hereditary hypotrichosis with recurrent skin vesicles	Pathogenic (May 03, 2021)
18-31001686-A-G		not specified	Uncertain significance (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DSC3	protein_coding	protein_coding	ENST00000360428	16	52808

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.28e-21	0.00650	125494	1	253	125748	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.648	526	486	1.08	0.0000250	5836
Missense in Polyphen		171	175.32	0.97534		2192
Synonymous	-1.78	206	176	1.17	0.00000883	1752
Loss of Function	0.580	34	37.9	0.898	0.00000176	521

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00375	0.00374
Ashkenazi Jewish	0.00	0.00
East Asian	0.000931	0.000925
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000717	0.000712
Middle Eastern	0.000931	0.000925
South Asian	0.00268	0.00265
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.
• Disease: DISEASE: Hypotrichosis and recurrent skin vesicles (HRSV) [MIM:613102]: A disorder characterized by hypotrichosis and the appearance of recurrent skin vesicle formation. Affected individuals show sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid are observed on the scalp and skin of most of the body. Mucosal vesicles are absent. {ECO:0000269|PubMed:19765682}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Recessive Scores

• pRec: 0.0822

Intolerance Scores

• loftool: 0.964
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.68

Haploinsufficiency Scores

• pHI: 0.185
• hipred: N
• hipred_score: 0.368
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.620

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dsc3
• 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); 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); normal phenotype; cellular phenotype

Gene ontology

• Biological process: in utero embryonic development;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;keratinization;cornification
• Cellular component: cornified envelope;extracellular region;cytoplasm;plasma membrane;cell-cell junction;membrane;integral component of membrane;cell junction;desmosome
• Molecular function: calcium ion binding