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GeneBe

DMD

dystrophin, the group of Zinc fingers ZZ-type|MicroRNA protein coding host genes

Basic information

Region (hg38): X:31097676-33339609

Previous symbols: [ "MRX85" ]

Links

ENSG00000198947 ∙ NCBI:1756 ∙ OMIM:300377 ∙ HGNC:2928 ∙ Uniprot:P11532 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Duchenne and Becker muscular dystrophy (Definitive), mode of inheritance: XL
  • Becker muscular dystrophy (Definitive), mode of inheritance: XLR
  • dilated cardiomyopathy 3B (Definitive), mode of inheritance: XLR
  • Duchenne muscular dystrophy (Definitive), mode of inheritance: XLR
  • Becker muscular dystrophy (Definitive), mode of inheritance: XL
  • dilated cardiomyopathy 3B (Definitive), mode of inheritance: XL
  • Duchenne muscular dystrophy (Definitive), mode of inheritance: XL
  • familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
  • non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
  • Becker muscular dystrophy (Supportive), mode of inheritance: XL
  • Duchenne muscular dystrophy (Supportive), mode of inheritance: XL
  • symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers (Supportive), mode of inheritance: XL
  • Duchenne muscular dystrophy (Definitive), mode of inheritance: XL
  • Duchenne muscular dystrophy (Strong), mode of inheritance: XL
  • progressive muscular dystrophy (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Duchenne muscular dystrophy; Becker muscular dystrophy; Cardiomyopathy, dilated, 3BXLCardiovascularIndividuals may present at varying ages and with varying degrees of severity, but due to risk of dilated cardiomyopathy, surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals as well as variant-positive females, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation; Gene therapy has been approved for Duchenne muscular dystrophyCardiovascular; Musculoskeletal; Neurologic; Ophthalmologic13249581; 6683357; 2879922; 3574369; 3612177; 3384440; 2404210; 2325103; 2180286; 1683155; 1518025; 8232953; 8361506; 7802009; 8198142; 8012195; 8789442; 9611069; 11726549; 9170407; 19367636; 19449031; 19367636; 20301298; 22428906; 22451200; 22609847; 22632414; 22650324; 23092449; 23299919; 37539981; 37577753
Cardiomyopathy is common in individuals, and has been specifically described as an isolated finding in females with relevant variants

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMD gene.

  • Duchenne muscular dystrophy (5564 variants)
  • not provided (2133 variants)
  • Cardiovascular phenotype (957 variants)
  • not specified (493 variants)
  • Dilated cardiomyopathy 3B (257 variants)
  • Cardiomyopathy;Dystrophin deficiency;Becker muscular dystrophy;Duchenne muscular dystrophy (152 variants)
  • Becker muscular dystrophy (148 variants)
  • Becker muscular dystrophy;Cardiomyopathy;Dystrophin deficiency;Duchenne muscular dystrophy (119 variants)
  • Becker muscular dystrophy;Dystrophin deficiency;Cardiomyopathy;Duchenne muscular dystrophy (95 variants)
  • Cardiomyopathy;Dystrophin deficiency;Duchenne muscular dystrophy;Becker muscular dystrophy (78 variants)
  • Dystrophin deficiency;Becker muscular dystrophy;Cardiomyopathy;Duchenne muscular dystrophy (73 variants)
  • Duchenne muscular dystrophy;Becker muscular dystrophy;Cardiomyopathy;Dystrophin deficiency (70 variants)
  • Cardiomyopathy;Becker muscular dystrophy;Duchenne muscular dystrophy;Dystrophin deficiency (66 variants)
  • Duchenne muscular dystrophy;Becker muscular dystrophy (66 variants)
  • Becker muscular dystrophy;Cardiomyopathy;Duchenne muscular dystrophy;Dystrophin deficiency (65 variants)
  • Qualitative or quantitative defects of dystrophin (58 variants)
  • Becker muscular dystrophy;Duchenne muscular dystrophy;Cardiomyopathy;Dystrophin deficiency (57 variants)
  • Dystrophin deficiency (53 variants)
  • Duchenne muscular dystrophy;Dystrophin deficiency;Becker muscular dystrophy;Cardiomyopathy (53 variants)
  • Dystrophin deficiency;Duchenne muscular dystrophy;Becker muscular dystrophy;Cardiomyopathy (51 variants)
  • Becker muscular dystrophy;Duchenne muscular dystrophy;Dilated cardiomyopathy 3B (39 variants)
  • Dystrophin deficiency;Cardiomyopathy;Duchenne muscular dystrophy;Becker muscular dystrophy (37 variants)
  • Dystrophin deficiency;Cardiomyopathy;Becker muscular dystrophy;Duchenne muscular dystrophy (32 variants)
  • Cardiomyopathy;Duchenne muscular dystrophy;Becker muscular dystrophy;Dystrophin deficiency (30 variants)
  • Dystrophin deficiency;Duchenne muscular dystrophy;Cardiomyopathy;Becker muscular dystrophy (27 variants)
  • Becker muscular dystrophy;Duchenne muscular dystrophy;Dystrophin deficiency;Cardiomyopathy (26 variants)
  • Dilated cardiomyopathy 3B;Becker muscular dystrophy;Duchenne muscular dystrophy (25 variants)
  • Dystrophin deficiency;Becker muscular dystrophy;Duchenne muscular dystrophy;Cardiomyopathy (25 variants)
  • Cardiomyopathy;Becker muscular dystrophy;Dystrophin deficiency;Duchenne muscular dystrophy (24 variants)
  • Becker muscular dystrophy;Dilated cardiomyopathy 3B;Duchenne muscular dystrophy (23 variants)
  • Duchenne muscular dystrophy;Becker muscular dystrophy;Dilated cardiomyopathy 3B (23 variants)
  • Duchenne muscular dystrophy;Dilated cardiomyopathy 3B;Becker muscular dystrophy (23 variants)
  • Abnormality of the musculature (22 variants)
  • Duchenne muscular dystrophy;Cardiomyopathy;Becker muscular dystrophy;Dystrophin deficiency (21 variants)
  • DMD-related condition (18 variants)
  • Dilated cardiomyopathy 3B;Duchenne muscular dystrophy;Becker muscular dystrophy (15 variants)
  • Primary dilated cardiomyopathy (15 variants)
  • Duchenne muscular dystrophy;Becker muscular dystrophy;Dystrophin deficiency;Cardiomyopathy (14 variants)
  • Duchenne muscular dystrophy;Cardiomyopathy;Dystrophin deficiency;Becker muscular dystrophy (13 variants)
  • Becker muscular dystrophy;Dystrophin deficiency;Duchenne muscular dystrophy;Cardiomyopathy (12 variants)
  • Becker muscular dystrophy;Duchenne muscular dystrophy (9 variants)
  • Duchenne muscular dystrophy;Dystrophin deficiency;Cardiomyopathy;Becker muscular dystrophy (8 variants)
  • Cardiomyopathy (7 variants)
  • Primary familial dilated cardiomyopathy (6 variants)
  • Cardiomyopathy;Duchenne muscular dystrophy;Dystrophin deficiency;Becker muscular dystrophy (6 variants)
  • Duchenne and Becker muscular dystrophy (6 variants)
  • Elevated circulating creatine kinase concentration (6 variants)
  • See cases (5 variants)
  • Primary familial hypertrophic cardiomyopathy (5 variants)
  • Inborn genetic diseases (5 variants)
  • Muscular dystrophy (5 variants)
  • Arrhythmogenic right ventricular cardiomyopathy (3 variants)
  • Dilated cardiomyopathy 1A (3 variants)
  • Familial restrictive cardiomyopathy (2 variants)
  • Hypertrophic cardiomyopathy (2 variants)
  • Color vision defect (2 variants)
  • Intermediate muscular dystrophy (2 variants)
  • Conduction disorder of the heart (2 variants)
  • Left ventricular noncompaction cardiomyopathy (2 variants)
  • Abnormality of neuronal migration (1 variants)
  • Shoulder girdle muscle weakness;EMG: myopathic abnormalities (1 variants)
  • Intellectual disability (1 variants)
  • Long QT syndrome (1 variants)
  • Proptosis;Pectus excavatum;Cardiomyopathy;Ptosis;Clinodactyly of the 5th finger (1 variants)
  • Elevated circulating creatine kinase concentration;Progressive proximal muscle weakness (1 variants)
  • Heart failure (1 variants)
  • Exertional myalgia, muscle stiffness and myoglobinuria (1 variants)
  • Becker muscular dystrophy;Dilated cardiomyopathy 3B (1 variants)
  • Dystrophinopathy (1 variants)
  • Becker muscular dystrophy, atypical (1 variants)
  • Restrictive cardiomyopathy (1 variants)
  • X-linked DMD-related dystrophinopathy (1 variants)
  • Long QT syndrome;Brugada syndrome (1 variants)
  • 9 conditions (1 variants)
  • Elevated circulating creatine kinase concentration;Atrial septal defect (1 variants)
  • Motor delay;Calf muscle hypertrophy;Proximal muscle weakness in lower limbs (1 variants)
  • Muscular atrophy (1 variants)
  • 6 conditions (1 variants)
  • Abnormal muscle fiber dystrophin expression;Calf muscle hypertrophy;Progressive muscle weakness;Primary dilated cardiomyopathy (1 variants)
  • Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
28
clinvar
1246
clinvar
35
clinvar
 1310
missense
4
clinvar
18
clinvar
1738
clinvar
207
clinvar
23
clinvar
 1990
nonsense
575
clinvar
107
clinvar
1
clinvar
 683
start loss
0
frameshift
532
clinvar
96
clinvar
2
clinvar
 630
inframe indel
2
clinvar
3
clinvar
29
clinvar
 34
splice donor/acceptor (+/-2bp)
202
clinvar
95
clinvar
6
clinvar
2
clinvar
 305
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
9
13
120
248
16
 406
non coding
?
    UTR, intron and other, non coding variants
8
clinvar
12
clinvar
121
clinvar
700
clinvar
394
clinvar
 1235
Total 1324 331 1925 2155 452

Highest pathogenic variant AF is 0.00000903

Variants in DMD

This is a list of pathogenic ClinVar variants found in the DMD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
X-31119334-A-C Dilated cardiomyopathy 3B Uncertain significance (Jan 13, 2018)915100
X-31119356-C-T Dilated cardiomyopathy 3B Likely benign (Jan 13, 2018)915101
X-31119591-C-T Dilated cardiomyopathy 3B Uncertain significance (Jan 15, 2018)915102
X-31119605-A-G Dilated cardiomyopathy 3B Uncertain significance (Jan 12, 2018)368199
X-31119651-G-A Dilated cardiomyopathy 3B Conflicting classifications of pathogenicity (Dec 01, 2022)915103
X-31119680-A-AAACTT Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368200
X-31119681-A-AACTT Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368201
X-31119816-A-T Dilated cardiomyopathy 3B Uncertain significance (Jan 13, 2018)915104
X-31119880-G-T Dilated cardiomyopathy 3B Likely benign (Apr 27, 2017)368203
X-31119880-G-GAA Dilated cardiomyopathy 3B Likely benign (Jun 14, 2016)368202
X-31119884-G-GAATT Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368204
X-31120002-C-T Dilated cardiomyopathy 3B Uncertain significance (Jan 12, 2018)912397
X-31120120-C-A Dilated cardiomyopathy 3B Benign (Jan 13, 2018)912398
X-31120136-T-C Dilated cardiomyopathy 3B Benign (Jan 12, 2018)368205
X-31120157-TTGAA-T Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368206
X-31120188-T-G Dilated cardiomyopathy 3B Benign (Jan 12, 2018)368207
X-31120214-T-C Dilated cardiomyopathy 3B Likely benign (Jan 13, 2018)912399
X-31120281-T-C Dilated cardiomyopathy 3B Benign (Jan 12, 2018)368208
X-31120327-T-TAACA Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368209
X-31120353-T-TCTTA Dilated cardiomyopathy 3B Likely benign (Jun 14, 2016)368210
X-31120464-G-T Dilated cardiomyopathy 3B Likely benign (Jan 13, 2018)368211
X-31120470-G-GTCTT Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368212
X-31120472-T-C Dilated cardiomyopathy 3B Benign (Jan 12, 2018)368213
X-31120490-G-GTTTA Dilated cardiomyopathy 3B Uncertain significance (Jun 14, 2016)368214
X-31120570-A-C Dilated cardiomyopathy 3B Uncertain significance (Jan 13, 2018)368215

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DMDprotein_codingprotein_codingENST00000357033 792241765
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.003.59e-1512567416541257440.000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-2.4315681.32e+31.190.00010024350
Missense in Polyphen260218.461.19013922
Synonymous-3.445744781.200.00003576671
Loss of Function10.7171650.1030.00001282656

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002620.00218
Ashkenazi Jewish0.000.00
East Asian0.00007280.0000544
Finnish0.00006320.0000462
European (Non-Finnish)0.0002470.000176
Middle Eastern0.00007280.0000544
South Asian0.0003260.000196
Other0.0002210.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin- associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission. {ECO:0000250|UniProtKB:P11531, ECO:0000269|PubMed:16710609}.;
Disease
DISEASE: Duchenne muscular dystrophy (DMD) [MIM:310200]: Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment. {ECO:0000269|PubMed:12632325, ECO:0000269|PubMed:24302611, ECO:0000269|PubMed:7981690, ECO:0000269|PubMed:8401582, ECO:0000269|PubMed:8817332, ECO:0000269|PubMed:9851445}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Becker muscular dystrophy (BMD) [MIM:300376]: A neuromuscular disorder characterized by dystrophin deficiency. It appears between the age of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Becker muscular dystrophy has a more benign course than Duchenne muscular dystrophy. {ECO:0000269|PubMed:10573008}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, X-linked 3B (CMD3B) [MIM:302045]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:12359139, ECO:0000269|PubMed:25340340, ECO:0000269|PubMed:9170407}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Ectoderm Differentiation;Striated Muscle Contraction;Extracellular matrix organization;Striated Muscle Contraction;Muscle contraction;agrin in postsynaptic differentiation;Non-integrin membrane-ECM interactions (Consensus)

Recessive Scores

pRec
0.764

Intolerance Scores

loftool
0.342
rvis_EVS
-0.84
rvis_percentile_EVS
11.28

Haploinsufficiency Scores

pHI
0.340
hipred
Y
hipred_score
0.698
ghis
0.502

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.578

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Dmd
Phenotype
adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype;

Zebrafish Information Network

Gene name
dmd
Affected structure
fast muscle cell
Phenotype tag
abnormal
Phenotype quality
detached from

Gene ontology

Biological process
regulation of heart rate;cytoskeleton organization;muscle organ development;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion;regulation of skeletal muscle contraction;muscle filament sliding;negative regulation of peptidyl-serine phosphorylation;cellular protein localization;cellular protein-containing complex assembly;response to muscle stretch;peptide biosynthetic process;muscle cell cellular homeostasis;muscle fiber development;cardiac muscle contraction;regulation of ryanodine-sensitive calcium-release channel activity;cardiac muscle cell action potential;regulation of voltage-gated calcium channel activity;negative regulation of peptidyl-cysteine S-nitrosylation;positive regulation of sodium ion transmembrane transporter activity
Cellular component
cytosol;cytoskeleton;cell surface;dystrophin-associated glycoprotein complex;syntrophin complex;lateral plasma membrane;Z disc;cell-substrate junction;filopodium;filopodium membrane;protein-containing complex;sarcolemma;costamere;neuron projection terminus;membrane raft;synapse;postsynaptic membrane
Molecular function
dystroglycan binding;actin binding;structural constituent of cytoskeleton;protein binding;zinc ion binding;structural constituent of muscle;myosin binding;vinculin binding;nitric-oxide synthase binding