Progressive muscular dystrophy

Summary

Progressive muscular dystrophy (MONDO:0016106) is a disease (an umbrella term covering 13 Mondo subtypes) caused by DMD (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

• Causal gene: DMD (GenCC Strong)
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 13
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive muscular dystrophy
Mondo ID	MONDO:0016106
Orphanet	206644
UMLS	C4551827
MedGen	1633060
GARD	0020360
Is cancer (heuristic)	no

Also known as: progressive muscular dystrophy

Data availability: 13 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 13 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy

Related subtypes (10): muscular dystrophy, Barnes type, muscular dystrophy, cardiac type, muscular dystrophy, Hemizygous lethal type, muscular dystrophy, Mabry type, muscular dystrophy, progressive Pectorodorsal, distal myopathy, congenital muscular dystrophy, Fukuda-Miyanomae-Nakata syndrome, LAMA2-related muscular dystrophy, DMD-related muscular dystrophy

Subtypes (13): facioscapulohumeral muscular dystrophy, congenital fibrosis of extraocular muscles, Bethlem myopathy, oculopharyngeal muscular dystrophy, X-linked myopathy with excessive autophagy, myopathy, myofibrillar, 9, with early respiratory failure, progressive scapulohumeroperoneal distal myopathy, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, myotonic dystrophy, Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome, oculopharyngodistal myopathy

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

13 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 uncertain significance, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11222	NM_004006.3(DMD):c.2302C>T (p.Arg768Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1704540	NM_004006.3(DMD):c.2168+2T>C	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723378	NM_004006.3(DMD):c.5771_5772del (p.Glu1924fs)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
2810377	NM_004006.3(DMD):c.5612dup (p.Ala1872fs)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
4081625	NM_004006.3(DMD):c.5611A>T (p.Lys1871Ter)	DMD	Pathogenic	criteria provided, single submitter
4293264	NM_004006.3(DMD):c.7327dup (p.Thr2443fs)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
4532188	NM_004006.3(DMD):c.9072G>A (p.Trp3024Ter)	DMD	Pathogenic	criteria provided, single submitter
2674867	NM_004006.3(DMD):c.960+1G>A	DMD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081626	NM_004006.3(DMD):c.6291-1G>T	DMD	Likely pathogenic	criteria provided, single submitter
1355209	NM_004006.3(DMD):c.2365G>A (p.Glu789Lys)	DMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1052902	NM_004006.3(DMD):c.7993A>G (p.Asn2665Asp)	DMD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2158685	NM_004006.3(DMD):c.8806C>G (p.Leu2936Val)	DMD	Uncertain significance	criteria provided, multiple submitters, no conflicts
4070907	Single allele	DMD	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DMD	Definitive	X-linked	Becker muscular dystrophy	12

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	gencc,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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT05747924	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)