DSC3

DSC3
Identifiers
Aliases	DSC3, CDHF3, DSC, DSC1, DSC2, DSC4, HT-CP, desmocollin 3
External IDs	OMIM: 600271; MGI: 1194993; HomoloGene: 1462; GeneCards: DSC3; OMA:DSC3 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q12.1 Start 30,989,365 bp[1] End 31,042,815 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 A2|18 11.11 cM Start 20,093,987 bp[2] End 20,135,408 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of thigh gingival epithelium skin of hip vulva human penis hair follicle nipple skin of arm skin of abdomen oral cavity Top expressed in epidermis skin of external ear hair follicle skin of back skin of abdomen lip molar mesenteric lymph nodes cornea conjunctival fornix More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding gamma-catenin binding metal ion binding Cellular component cell-cell junction integral component of membrane desmosome membrane cornified envelope plasma membrane cell junction extracellular region cytoplasm Biological process homophilic cell adhesion via plasma membrane adhesion molecules protein stabilization cell adhesion keratinization cornification in utero embryonic development cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1825 13507 Ensembl ENSG00000134762 ENSMUSG00000059898 UniProt Q14574 P55850 RefSeq (mRNA) NM_024423 NM_001941 NM_001291809 NM_007882 RefSeq (protein) NP_001932 NP_077741 NP_001278738 NP_031908 Location (UCSC) Chr 18: 30.99 – 31.04 Mb Chr 18: 20.09 – 20.14 Mb PubMed search [3] [4]
Wikidata
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Desmocollin-3 is a protein that in humans is encoded by the DSC3 gene.^[5][6][7]

Gene

The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Alternative splicing results in two transcript variants encoding distinct isoforms.^[7]

Function

Desmocollin-3 is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation.^[7] The loss of these components leads to a lack of adhesion and a gain of cellular mobility.^[8]

Clinical significance

Breast cancer

Through the process of epigenetic silencing, the expression of the desmocollin-3 protein is down regulated in many breast cancers.^[8]

Hereditary hypotrichosis

A consanguineous Afghan family in which 3 sisters, 12 to 18 years of age, and their 5-year-old brother displayed features of hereditary hypotrichosis, associated with vesicles on the scalp and skin.^[9] At birth, scalp hair was present, and after ritual shaving at 1 week of age, scalp hair grew back; however, the hair was fragile and began falling out at 2 to 3 months of age, eventually leaving only sparse hair on the scalp. Vesicles that were less than 1 cm in diameter were observed on the scalp and skin of most of the body, occasionally disappearing but then reappearing; intermittently, the vesicles would burst with a release of fluid, leaving scars on the site that took 3 to 4 months to heal. There were no mucosal vesicles. Upon examination, the affected individuals were nearly devoid of eyebrows, eyelashes, axillary hair, and body hair. Teeth, nails, palms, soles, sweating, and hearing were normal, as was electrocardiography. Serum IgA, IgE, and IgD were measured in 1 individual and showed no change compared to controls. The parents were clinically unaffected. A scalp biopsy of the 18-year-old sister showed slight follicular plugging, mild perivascular and periadnexal inflammatory cell presence, and normal hair follicles. The sebaceous glands appeared morphologically normal and connected to the hair follicles.^[9]

Mapping

Genotyping and linkage analysis of the consanguineous Afghan family resulted in a maximum 2-point load score of 2.68 (theta = 0.0) at markers D18S36 and D18S547. Multipoint analysis generated a maximum load score of 3.30 at marker D18S877. Recombination events defined an 8.30-cM critical interval on chromosome 18q12.1, flanked by markers D18S66 and D18S1139, containing 30 genes.^[9]

Molecular genetics

A nonsense mutation in the DSC3 gene (600271.0001) mapping to chromosome 18q12.1 was identified in the consanguineous Afghan family with hypotrichosis and recurrent skin vesicles (613102). The unaffected parents and 3 healthy siblings were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls.^[9] In affected members of this family with hypotrichosis were homozygous for a 2129T-G transversion in exon 14 of the DSC3 gene, resulting in a leu710-to-ter (L710X; Ayub et al. 2009) substitution at the junction of the transmembrane and the C-terminal cytoplasmic domain, predicted to cause premature termination and nonsense mediated decay of the mRNA or instability of the truncated protein. The unaffected parents and 3 healthy siblings were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls.^[9]

Interactions

DSC3 has been shown to interact with PKP3.^[10]

References

Further reading