DSG4 (Desmoglein 4)
Key adhesion protein in hair follicle differentiation and hereditary hypotrichosis
Gene Information Card
| Symbol | DSG4 |
|---|---|
| Full Name | Desmoglein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.1 |
| NCBI Gene ID | 147409 ncbi.nlm.nih.gov/gene/147409 |
| Ensembl ID | ENSG00000175065 |
| UniProt ID | Q86SJ6 |
| OMIM ID | 607892 |
| HGNC ID | 21307 |
| Aliases | CDHF13, HTSS, LAH, LYGH, HYPT6 |
Description
DSG4 encodes desmoglein 4, a calcium-binding transmembrane glycoprotein of the cadherin superfamily and a component of desmosomes. It is predominantly expressed in the hair follicle and plays a critical role in cell-cell adhesion and differentiation of the hair shaft. Mutations in DSG4 cause hereditary hypotrichosis simplex (HTS) and localized autosomal recessive hypotrichosis (LAH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary hypotrichosis simplex (HTS) | Loss-of-function mutations impair desmosome assembly in hair follicle keratinocytes, leading to defective hair shaft formation and progressive hair loss. | OMIM #607903; ClinVar |
| Localized autosomal recessive hypotrichosis (LAH) | Biallelic DSG4 mutations disrupt adhesion between inner root sheath and hair shaft, causing sparse, fragile hair. | OMIM #607903; PubMed 15133497 |
| Hypotrichosis 6 (HYPT6) | Nonsense or frameshift variants result in truncated desmoglein 4, compromising desmosomal integrity and hair growth. | OMIM #607903; HGNC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Hair follicle | 18.3 | High |
| Esophagus | 6.2 | Low |
| Tongue | 4.8 | Low |
| Prostate | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.0 | High expression |
| NHEK (normal human epidermal keratinocytes) | 14.2 | High expression |
| A431 (epidermoid carcinoma) | 8.5 | Moderate expression |
| MCF7 (breast cancer) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1189C>T (p.Arg397*) | Nonsense | Rare (found in consanguineous families) | Premature stop; loss of transmembrane domain; loss of function |
| c.2022_2023delCT (p.Cys675*) | Frameshift | Rare | Truncated protein; impaired desmosome assembly |
| c.553G>A (p.Gly185Arg) | Missense | Rare | Disrupts calcium-binding site; reduced adhesion |
| c.2668C>T (p.Arg890Trp) | Missense | Rare | Alters extracellular cadherin repeat; dominant-negative effect suspected |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg397*, p.Cys675*) lead to truncated, non-functional desmoglein 4, causing autosomal recessive hypotrichosis.
Gain of Function (GOF)
No gain-of-function mutations reported for DSG4.
Dominant Negative (DN)
Missense variants such as p.Arg890Trp may exert dominant-negative effects by interfering with wild-type desmoglein 4 incorporation into desmosomes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell adhesion molecules (CAMs) – KEGG hsa04514
• Desmosome assembly – Reactome R-HSA-157858
• Keratinocyte differentiation – Reactome R-HSA-6809371
Protein Summary
Desmoglein 4 is a 1040-amino acid transmembrane cadherin with four extracellular cadherin repeats, a transmembrane domain, and a cytoplasmic tail that anchors to intermediate filaments via plakoglobin and desmoplakin. It is specifically expressed in the suprabasal layers of the hair follicle and is essential for maintaining the structural integrity of the hair shaft. Loss of function leads to hypotrichosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DSG4 Knockout HEK293 Cell Line | EDJ-KQ10601 | Human | 147409 | Details Get a Quote |
| DSG4 Knockout HeLa Cell Line | EDJ-KQ58574 | Human | 147409 | Details Get a Quote |
| DSG4 Knockout A-549 Cell Line | EDJ-KQ67064 | Human | 147409 | Details Get a Quote |
| DSG4 Knockout HCT 116 Cell Line | EDJ-KQ75465 | Human | 147409 | Details Get a Quote |
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