DMD
Chr XXLRX-linkeddystrophin
Also known as: BMD, CMD3B, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268
The dystrophin protein forms a component of the dystrophin-glycoprotein complex that bridges the inner cytoskeleton and extracellular matrix in muscle cells. Mutations cause X-linked recessive Duchenne muscular dystrophy, Becker muscular dystrophy, and dilated cardiomyopathy through loss of function mechanisms. Deletions, duplications, and point mutations all contribute to disease pathogenesis.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Tolerant to missense variation
Dystrophin. Frameshift/nonsense mutations cause complete LOF (Duchenne). In-frame deletions preserving partial function cause milder Becker phenotype. This is a classic LOF gene; the Badonyi GOF prediction is incorrect.
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
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
500 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 | 113 | 2 | 23 | 0 | 138 |
Likely Pathogenic | 42 | 0 | 12 | 0 | 54 |
VUS | 1 | 186 | 9 | 0 | 196 |
Likely Benign | 0 | 4 | 54 | 52 | 110 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 156 | 192 | 99 | 52 | 500 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DMD · 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
Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD
ACTIVE NOT RECRUITINGEvaluation of the Role of miR-1 in the Pathogenesis and as a Biomarker in Muscular Dystrophies and Congenital Myopathies
RECRUITINGUrinary Titin Biomarker in DMD
RECRUITINGAFFINITY DUCHENNE: RGX-202 Gene Therapy in Participants With Duchenne Muscular Dystrophy (DMD)
RECRUITINGA Study of SGT-003 Gene Therapy in Duchenne Muscular Dystrophy (INSPIRE DUCHENNE)
RECRUITINGModulation of SERCA2a of Intra-Myocytic Calcium Trafficking in Cardiomyopathy Secondary to Duchenne Muscular Dystrophy
RECRUITINGSpastic Myopathy in Adults With Cerebral Palsy
RECRUITINGA Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy
RECRUITINGA Study to Investigate the Safety and Biodistribution of a Single Intrathecal (IT) Injection of INS1201 in Ambulatory Males With Duchenne Muscular Dystrophy (DMD)
RECRUITINGSkeletal Maturation and Endocrine Health in Young Adults
ENROLLING BY INVITATIONMolecular Analysis of Patients With Neuromuscular Disease
RECRUITINGDevelopment of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
RECRUITINGExternal Resources
Links to major genomics databases and tools