Neuromuscular disease caused by qualitative or quantitative defects of dystrophin

Summary

Neuromuscular disease caused by qualitative or quantitative defects of dystrophin (MONDO:0016147) is a disease with 1 cohort gene and 7 clinical trials. Top therapeutic interventions include ataluren and arginine.

At a glance

• Cohort genes: 1
• ClinVar variants: 236
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuromuscular disease caused by qualitative or quantitative defects of dystrophin
Mondo ID	MONDO:0016147
Orphanet	207085
UMLS	C5679787
MedGen	1826053
GARD	0002031
Is cancer (heuristic)	no

Also known as: dystrophinopathy · qualitative or quantitative defects of dystrophin

Data availability: 236 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of dystrophin

Related subtypes (18): sarcoglycanopathy, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, caveolinopathy, neuromuscular disease caused by qualitative or quantitative defects of perlecan, neuromuscular disease caused by qualitative or quantitative defects of TRIM32, neuromuscular disease caused by qualitative or quantitative defects of myofibrillar proteins, neuromuscular disease caused by qualitative or quantitative defects of titin, neuromuscular disease caused by qualitative or quantitative defects of telethonin, neuromuscular disease caused by qualitative or quantitative defects of alpha-actin, neuromuscular disease caused by qualitative or quantitative defects of nebulin, neuromuscular disease caused by qualitative or quantitative defects of beta-myosin heavy chain (MYH7), neuromuscular disease caused by qualitative or quantitative defects of selenoprotein N1, neuromuscular disease caused by qualitative or quantitative defects of plectin, neuromuscular disease caused by qualitative or quantitative defects of protein SERCA1, neuromuscular disease caused by qualitative or quantitative defects of tropomyosin, neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan, alpha-actinopathy, collagen 6-related myopathy

Subtypes (2): dilated cardiomyopathy 3B, isolated asymptomatic elevation of creatine phosphokinase

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

236 retrieved; paginated sample, class counts are floors:

144 pathogenic, 60 likely pathogenic, 24 pathogenic/likely pathogenic, 4 uncertain significance, 4 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1050819	NC_000023.10:g.(32430031_32456357)_(32563452_32583818)del	DMD	Pathogenic	criteria provided, single submitter
1065130	NC_000023.10:g.(31697704_31747747)_(31747866_31792076)del	DMD	Pathogenic	criteria provided, single submitter
1098782	NC_000023.10:g.(32328394_32360216)_(32536249_32563275)del	DMD	Pathogenic	criteria provided, single submitter
1098794	NC_000023.10:g.(31792310_31838091)_(31854937_31893304)dup	DMD	Pathogenic	criteria provided, single submitter
1098826	NC_000023.10:g.(31854937_31893304)_(31950345_31986455)del	DMD	Pathogenic	criteria provided, single submitter
11225	NM_004006.3(DMD):c.433C>T (p.Arg145Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11282	NM_004006.3(DMD):c.9568C>T (p.Arg3190Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11283	NM_004006.3(DMD):c.3940C>T (p.Arg1314Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1192268	NC_000023.10:g.(32509636_32519871)_(32717411_32827609)del	DMD	Pathogenic	criteria provided, single submitter
1217262	NC_000023.10:g.(31697704_31747747)_(31893491_31947712)del	DMD	Pathogenic	criteria provided, single submitter
1301349	NC_000023.10:g.(31645980_31676106)_(31950345_31986455)del	DMD	Pathogenic	criteria provided, single submitter
1321345	NC_000023.10:g.(32663270_32715986)_(32717411_32827609)del	DMD	Pathogenic	criteria provided, single submitter
1322493	NM_004006.3(DMD):c.1267C>T (p.Gln423Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1324248	NM_004006.3(DMD):c.9362-1215A>G	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1331477	NC_000023.10:g.(32519960_32536124)_(32862978_32867844)del	DMD	Pathogenic	criteria provided, single submitter
1339730	NC_000023.10:g.(31525571_31645789)_(31986632_32235032)dup	DMD	Pathogenic	criteria provided, single submitter
1339733	NC_000023.10:g.(32862978_32867844)_(32867938_33038255)dup	DMD	Pathogenic	criteria provided, single submitter
1370216	NM_004006.3(DMD):c.5104_5105del (p.Leu1702fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458082	NM_004006.3(DMD):c.3103C>T (p.Gln1035Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
166864	NM_004006.3(DMD):c.883C>T (p.Arg295Ter)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1677191	NC_000023.10:g.(31525571_31645789)_(31838201_31854834)dup	DMD	Pathogenic	criteria provided, single submitter
1683299	NC_000023.10:g.(31854937_31893304)_(31986632_32235032)del	DMD	Pathogenic	criteria provided, single submitter
1696238	NM_004006.3(DMD):c.4500del (p.Gln1501fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1696241	NC_000023.10:g.(32867938_33038255)_(33038318_33229398)dup	DMD	Pathogenic	criteria provided, single submitter
1698468	NM_004006.3(DMD):c.9184del (p.Glu3062fs)	DMD	Pathogenic	criteria provided, single submitter
1704536	NC_000023.10:g.(31838201_31854834)_(31950345_31986455)dup	DMD	Pathogenic	criteria provided, single submitter
1704537	NC_000023.10:g.(31792310_31838091)_(31947863_31950196)del	DMD	Pathogenic	criteria provided, single submitter
1704540	NM_004006.3(DMD):c.2168+2T>C	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705236	NC_000023.10:g.(32591964_32613873)_(32632571_32662248)dup	DMD	Pathogenic	criteria provided, single submitter
1722391	NC_000023.10:g.(31986632_32235032)_(32519960_32536124)dup	DMD	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMD	Orphanet:154	Familial isolated dilated cardiomyopathy
DMD	Orphanet:206546	Symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers
DMD	Orphanet:777	X-linked non-syndromic intellectual disability
DMD	Orphanet:98895	Becker muscular dystrophy
DMD	Orphanet:98896	Duchenne muscular dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DMD	Dystrophin	Anchors the extracellular matrix to the cytoskeleton via F-actin.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
skeletal muscle tissue of rectus abdominis	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMD	295	ubiquitous	marker	trigeminal ganglion, skeletal muscle tissue of rectus abdominis, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DMD	2,479

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DMD	P11532	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Striated Muscle Contraction	1	308.6×	0.005	DMD
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.005	DMD
Non-integrin membrane-ECM interactions	1	154.3×	0.006	DMD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of muscle system process	1	16852.0×	7e-04	DMD
regulation of cellular response to growth factor stimulus	1	16852.0×	7e-04	DMD
cardiac muscle cell action potential	1	8426.0×	1e-03	DMD
regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	1	4213.0×	0.001	DMD
peptide biosynthetic process	1	4213.0×	0.001	DMD
regulation of skeletal muscle contraction	1	2808.7×	0.001	DMD
regulation of calcium ion transmembrane transport	1	2106.5×	0.002	DMD
synaptic signaling	1	1532.0×	0.002	DMD
regulation of sodium ion transmembrane transport	1	1053.2×	0.003	DMD
muscle cell development	1	936.2×	0.003	DMD
response to muscle stretch	1	766.0×	0.003	DMD
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	674.1×	0.003	DMD
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.003	DMD
muscle cell cellular homeostasis	1	648.1×	0.003	DMD
motile cilium assembly	1	581.1×	0.003	DMD
maintenance of blood-brain barrier	1	481.5×	0.003	DMD
regulation of heart rate	1	468.1×	0.003	DMD
cardiac muscle contraction	1	401.2×	0.003	DMD
skeletal muscle tissue development	1	290.6×	0.005	DMD
neuron development	1	255.3×	0.005	DMD
positive regulation of neuron differentiation	1	198.3×	0.006	DMD
muscle organ development	1	166.8×	0.007	DMD
positive regulation of neuron projection development	1	137.0×	0.008	DMD
protein-containing complex assembly	1	113.9×	0.009	DMD
intracellular protein localization	1	104.7×	0.010	DMD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DMD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DMD

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DMD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01557400	PHASE3	COMPLETED	Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
NCT01388764	PHASE1	COMPLETED	Safety, Tolerability and Effects of L-Arginine in Boys With Dystrophinopathy on Corticosteroids
NCT02069756	Not specified	RECRUITING	The Duchenne Registry
NCT07125898	Not specified	NOT_YET_RECRUITING	Decoding Central Defects in Dystrophinopathies From Diagnostic to Remediation
NCT07580365	Not specified	NOT_YET_RECRUITING	VirtualPark_Pediatric
NCT07609394	Not specified	RECRUITING	Duchenne Electronic Health Record Study
NCT02146586	Not specified	UNKNOWN	Clinical Evaluator Outcomes Reliability Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATALUREN	4	1
ARGININE	3	1