DST
Chr 6ARdystonin
The DST protein is a cytoskeletal linker that integrates intermediate filaments, actin, and microtubule networks, anchoring intermediate filaments to the actin cytoskeleton in neural and muscle cells and keratin filaments to hemidesmosomes in epithelial cells. Autosomal recessive mutations cause congenital myopathy with contractures, lethal congenital contracture syndrome, hereditary sensory and autonomic neuropathy type VI, and epidermolysis bullosa simplex with skin blistering. This gene is highly constrained against loss-of-function variants, reflecting its critical role in maintaining cytoskeletal integrity across multiple tissue types including skin, muscle, and peripheral nerves.
Definitive — sufficient evidence for diagnostic panels
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 16 | 0 | 3 | 0 | 19 |
Likely Pathogenic | 4 | 0 | 0 | 0 | 4 |
VUS | 1 | 92 | 8 | 12 | 113 |
Likely Benign | 0 | 3 | 11 | 47 | 61 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 21 | 95 | 24 | 59 | 200 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DST · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Alzheimer's Disease Multinuclear Imaging Neuro-Enhanced Resolution (AD-MINER)
RECRUITINGNovel Triple-dose Tuberculosis Retreatment Regimen
RECRUITINGIndividualized Treatments in Adults With Relapsed/Refractory Cancers
ACTIVE NOT RECRUITINGCognitive Decline and Underlying Mechanisms in Symptomatic Intracranial Artery Stenosis Patients: A Cohort Study
RECRUITINGHigh Protein Diet on Transcriptomic, Metabolomics, Hepatic and Pancreatic Fat Anatomy and Physiology in Asian Indians With Pre-diabetes
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools