DST (Dystonin) Gene
A key gene encoding cytoskeletal linker proteins, with roles in neuronal and epidermal integrity; mutations cause hereditary sensory and autonomic neuropathy and epidermolysis bullosa simplex.
Gene Information Card
| Symbol | DST |
|---|---|
| Full Name | Dystonin |
| Gene Type | Protein coding |
| Chromosomal Location | 6p12.1 |
| NCBI Gene ID | 667 ncbi.nlm.nih.gov/gene/667 |
| Ensembl ID | ENSG00000151914 |
| UniProt ID | Q03001 |
| OMIM ID | 113810 |
| HGNC ID | 1090 |
| Aliases | BPAG1, BPA, CATX-15, D6S1101, DMH, DT, EBS3, HSAN6, MACF2 |
Description
The DST gene encodes dystonin, a large cytoskeletal linker protein belonging to the plakin family. Dystonin crosslinks intermediate filaments to actin microfilaments and microtubules, maintaining cellular integrity in neurons and epithelial cells. Alternative splicing generates multiple isoforms (e.g., BPAG1e in skin, BPAG1a in neurons). Mutations in DST cause hereditary sensory and autonomic neuropathy type 6 (HSAN6) and epidermolysis bullosa simplex 3 (EBS3), with evidence from ClinVar and OMIM.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type 6 (HSAN6) | Loss of dystonin function disrupts neuronal cytoskeletal organization, leading to sensory and autonomic neuron degeneration. | ClinVar, OMIM #614653 |
| Epidermolysis bullosa simplex 3 (EBS3) | Defective dystonin in basal keratinocytes compromises hemidesmosome integrity, causing skin fragility and blistering. | ClinVar, OMIM #113810 |
| Dystonia (rare association) | Missense variants may alter dystonin-mediated cytoskeletal dynamics in the basal ganglia. | OMIM #113810, limited case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Low |
| Peripheral nerve | 15.1 | Medium |
| Skeletal muscle | 6.4 | Low |
| Heart | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocytes) | 18.3 | High expression; relevant for EBS studies |
| SH-SY5Y (neuroblastoma) | 9.7 | Moderate; used in neuronal isoform analysis |
| HEK293 | 4.2 | Low baseline; suitable for overexpression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.6898C>T (p.Arg2300*) | Nonsense | <0.01% | Loss of function; associated with HSAN6 |
| c.7402G>A (p.Gly2468Arg) | Missense | <0.01% | Dominant negative; linked to EBS3 |
| c.5578_5579del (p.Leu1860Valfs*12) | Frameshift | <0.01% | Loss of function; reported in HSAN6 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg2300*, p.Leu1860Valfs*12) lead to truncated dystonin, causing HSAN6 via neuronal cytoskeletal failure.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for DST.
Dominant Negative (DN)
Missense variants like p.Gly2468Arg in the plakin domain disrupt hemidesmosome assembly, causing EBS3 in a dominant negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hemidesmosome assembly (Reactome: R-HSA-446107)
• Intermediate filament organization (Reactome: R-HSA-6809371)
• Cell junction organization (Reactome: R-HSA-446353)
Protein Summary
Dystonin (UniProt Q03001) is a 280–300 kDa plakin family protein with multiple isoforms. It contains an N-terminal actin-binding domain (calponin homology), a plakin domain, a coiled-coil rod domain, and a C-terminal intermediate filament-binding domain. In neurons, dystonin links neurofilaments to the actin cytoskeleton; in keratinocytes, the BPAG1e isoform anchors keratin filaments to hemidesmosomes. Post-translational modifications include phosphorylation, which regulates subcellular localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DST Knockout HEK293 Cell Line | EDJ-KQ4147 | Human | 667 | Details Get a Quote |
| NDST1 Knockout HEK293 Cell Line | EDJ-KQ4951 | Human | 3340 | Details Get a Quote |
| NDST2 Knockout HEK293 Cell Line | EDJ-KQ6262 | Human | 8509 | Details Get a Quote |
| NDST3 Knockout HEK293 Cell Line | EDJ-KQ6555 | Human | 9348 | Details Get a Quote |
| DSTYK Knockout HEK293 Cell Line | EDJ-KQ8222 | Human | 25778 | Details Get a Quote |
| NDST2 Knockout A-549 Cell Line | EDJ-KQ30145 | Human | 8509 | Details Get a Quote |
| NDST2 Knockout HeLa Cell Line | EDJ-KQ30147 | Human | 8509 | Details Get a Quote |
| DSTYK Knockout A-549 Cell Line | EDJ-KQ34120 | Human | 25778 | Details Get a Quote |
| DSTYK Knockout HCT 116 Cell Line | EDJ-KQ34121 | Human | 25778 | Details Get a Quote |
| DSTYK Knockout HeLa Cell Line | EDJ-KQ34122 | Human | 25778 | Details Get a Quote |
| DST Knockout A-549 Cell Line | EDJ-KQ26582 | Human | 667 | Details Get a Quote |
| DST Knockout HCT 116 Cell Line | EDJ-KQ26583 | Human | 667 | Details Get a Quote |
| DST Knockout HeLa Cell Line | EDJ-KQ26584 | Human | 667 | Details Get a Quote |
| NDST1 Knockout HeLa Cell Line | EDJ-KQ26602 | Human | 3340 | Details Get a Quote |
| NDST1 Knockout A-549 Cell Line | EDJ-KQ27817 | Human | 3340 | Details Get a Quote |
Displaying Records 1 To 15 Of 28 Records
