DMD
Chr XXLRX-linkeddystrophin
Also known as: BMD, CMD3B, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268
This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]
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.1
This gene — mechanism propensity
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.
References
ClinVar Variant Classifications
0 submitted variants 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.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
ACTIVE NOT RECRUITINGLong Term Follow-up for RGX-202
ENROLLING BY INVITATIONPBGENE-DMD Phase 1/2a Safety and Preliminary Efficacy Study in Duchenne Muscular Dystrophy (FUNCTION-DMD)
RECRUITINGA Study to Evaluate the Safety and Tolerability of GEN6050X in Duchenne Muscular Dystrophy.
ACTIVE NOT RECRUITINGVariability in Analgesic Response to Ibuprofen
RECRUITINGMicrodystrophin Gene Transfer Study in Adolescents and Children With DMD
ACTIVE NOT RECRUITINGMotor Outcomes to Validate Evaluations in FSHD (MOVE FSHD)
RECRUITINGSkeletal Maturation and Endocrine Health in Young Adults
ENROLLING BY INVITATIONPhase 2 Study of EDG-5506 in Children and Adolescents With Duchenne Muscular Dystrophy Previously Treated With Gene Therapy
ACTIVE NOT RECRUITINGAn Observational Study Comparing Delandistrogene Moxeparvovec (ELEVIDYS) With Standard of Care in Participants With Duchenne Muscular Dystrophy
ENROLLING BY INVITATIONA Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of Single Intravenous Infusion of JWK007 in Patients With Duchenne Muscular Dystrophy (DMD)
ACTIVE NOT RECRUITINGA Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy
RECRUITINGExternal Resources
Links to major genomics databases and tools