DMD

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]

Full Name

Dystrophin

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.

Biological Process

Cardiac muscle cell action potential Source: BHF-UCL
Cardiac muscle contraction Source: BHF-UCL
Cellular protein-containing complex assembly Source: BHF-UCL
Cellular protein localization Source: BHF-UCL
Maintenance of blood-brain barrier Source: ARUK-UCL
Motile cilium assembly Source: BHF-UCL
Muscle cell cellular homeostasis Source: BHF-UCL
Muscle cell development Source: BHF-UCL
Muscle organ development Source: ProtInc
Negative regulation of peptidyl-cysteine S-nitrosylation Source: BHF-UCL
Negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
Peptide biosynthetic process Source: UniProtKB
Positive regulation of neuron differentiation Source: BHF-UCL
Positive regulation of neuron projection development Source: BHF-UCL
Positive regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
Regulation of cellular response to growth factor stimulus Source: BHF-UCL
Regulation of heart rate Source: BHF-UCL
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
Regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
Regulation of skeletal muscle contraction Source: BHF-UCL
Regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion Source: BHF-UCL
Regulation of voltage-gated calcium channel activity Source: BHF-UCL
Response to muscle stretch Source: BHF-UCL

Cellular Location

Cytoskeleton; Sarcolemma; Postsynaptic cell membrane. In muscle cells, sarcolemma localization requires the presence of ANK2, while localization to costameres requires the presence of ANK3. Localizes to neuromuscular junctions (NMJs). In adult muscle, NMJ localization depends upon ANK2 presence, but not in newborn animals.

Involvement in disease

Duchenne muscular dystrophy (DMD):
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.
Becker muscular dystrophy (BMD):
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.
Cardiomyopathy, dilated, X-linked 3B (CMD3B):
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.