DSG4
Basic information
Region (hg38): 18:31376777-31414912
Links
Phenotypes
GenCC
Source:
- monilethrix (Supportive), mode of inheritance: AD
- hypotrichosis simplex (Supportive), mode of inheritance: AD
- hypotrichosis 6 (Definitive), mode of inheritance: AR
- hypotrichosis 6 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
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
- Inborn_genetic_diseases (149 variants)
- Hypotrichosis_6 (94 variants)
- not_provided (85 variants)
- DSG4-related_disorder (24 variants)
- not_specified (1 variants)
- Ectodermal_dysplasia (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. These statistics are base on transcript: NM_000177986.5. 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 33 | 44 | ||||
missense | 160 | 33 | 199 | |||
nonsense | 4 | |||||
start loss | 0 | |||||
frameshift | 8 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
Total | 11 | 5 | 170 | 66 | 5 |
Highest pathogenic variant AF is 0.000101611535
GnomAD
Source:
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:
- 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
- ghis
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