Duchenne muscular dystrophy

Summary

Duchenne muscular dystrophy (MONDO:0010679) is a disease caused by DMD (GenCC Definitive), with 13 cohort genes (47 GWAS associations across 2 studies) and 363 clinical trials. The dominant Reactome pathway is Formation of the dystrophin-glycoprotein complex (DGC) (3 cohort genes). Top therapeutic interventions include ataluren, eteplirsen, and delandistrogene moxeparvovec.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: DMD (GenCC Definitive)
• Cohort genes: 13
• GWAS associations: 47
• ClinVar variants: 8,709
• Phenotypes (HPO): 15
• Clinical trials: 363

Clinical features

Epidemiology

Prevalence records

15 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.8	Worldwide	Validated
Prevalence at birth	1-9 / 100 000	9.9	Worldwide	Validated
Lifetime Prevalence	1-9 / 100 000	7.66	Egypt	Validated
Point prevalence	1-9 / 100 000	4.14	United Kingdom	Validated
Point prevalence	1-9 / 100 000	1.7	Italy	Validated
Point prevalence	1-9 / 100 000	4.26	Ireland	Validated
Point prevalence	1-9 / 100 000	3.56	Japan	Validated
Point prevalence	1-9 / 1 000 000	0.47	South Africa	Validated
Point prevalence	1-9 / 100 000	2.75	Denmark	Validated
Point prevalence	1-9 / 100 000	2.59	Puerto rico	Validated
Prevalence at birth	1-5 / 10 000	14	United States	Validated
Prevalence at birth	1-5 / 10 000	12	Netherlands	Validated
Prevalence at birth	1-5 / 10 000	10.5	Canada	Validated
Prevalence at birth	1-9 / 100 000	9.7	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	8.2	Ireland	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0001371	Flexion contracture	Very frequent (80-99%)
HP:0001638	Cardiomyopathy	Very frequent (80-99%)
HP:0002093	Respiratory insufficiency	Very frequent (80-99%)
HP:0002515	Waddling gait	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003323	Progressive muscle weakness	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0008981	Calf muscle hypertrophy	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Duchenne muscular dystrophy
Mondo ID	MONDO:0010679
MeSH	D020388
OMIM	310200
Orphanet	98896
DOID	DOID:11723
ICD-11	1479561744
NCIT	C75482
SNOMED CT	76670001
UMLS	C0013264
MedGen	3925
GARD	0006291
MedDRA	10013801
NORD	1065
Is cancer (heuristic)	no

Also known as: DMD · Duchenne muscular dystrophy · Duchenne muscular dystrophy, X-linked recessive · muscular dystrophy, Duchenne type · severe dystrophinopathy, Duchenne type

Data availability: 8,709 ClinVar variants · 47 GWAS associations (2 studies) · 4 GenCC gene-disease records · 184 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › DMD-related muscular dystrophy › Duchenne muscular dystrophy

Related subtypes (1): Becker muscular dystrophy

Genetics & variants

GWAS landscape

47 GWAS associations across 2 studies. Top hits map to 25 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2725797	7e-09	LINC02694	?
rs710160	5e-08	SHKBP1	?
rs74643788	5e-08	XYLT1	?
rs12547243	2e-07	ADCY8	?
rs35693284	2e-07	RN7SL551P - CYB5A	?
rs1698919	4e-07	BDP1P - RNA5SP461	?
rs56979833	4e-07	NCAPGP2 - SYNGR2P1	?
rs12524310	9e-07	Y_RNA - ERVH-3	?
rs1078793	1e-06	TBRG4 - RAMP3	?
rs11017928	1e-06	DOCK1	?
rs149640	1e-06	RGS6	?
rs17567824	1e-06	ADCY1	?
rs754118	1e-06	PTPN1	?
rs6788567	2e-06	MAT2AP1 - LINC02042	?
rs72737007	2e-06	LINC02112 - ATPSCKMT	?
rs73262722	2e-06	UNCX - MICALL2	?
rs7108263	4e-06	LINC02714 - LINC02697	?
rs6891905	4e-06	SPEF2	?
rs77093473	5e-06	NSG2 - LINC01411	?
rs201158842	5e-06	SLC25A48	?
rs78864163	6e-06	SATB1, TBC1D5	?
rs3822095	6e-06	SNCA	?
rs6736607	6e-06	SLC8A1, SLC8A1-AS1	?
rs1426040	7e-06	CLSTN2	?
rs61903333	7e-06	RN7SL435P - OR5AN2P	?
rs6499854	7e-06	NUP93	?
rs12451924	7e-06	SLFN12L	?
rs11641605	7e-06	LINC02141	?
rs841163	8e-06	OR14A2	?
rs35396788	8e-06	TAPT1-AS1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST006286	Weiss RB	2018	243	0	Long-range genomic regulators of THBS1 and LTBP4 modify disease severity in Duchenne muscular dystrophy.
GCST90274731	Flanigan KM	2023	0	0	A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	33

MAF distribution

Bucket	Variants
common (>=0.05)	36
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	25
intergenic_variant	8
3_prime_UTR_variant	2
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2725797	15	38817032	G>A,C	0.05	intron_variant	LINC02694	7e-09	Tier 4: intronic/intergenic
rs710160	19	40581585	T>A,C,G	0.05	intron_variant	SHKBP1	5e-08	Tier 4: intronic/intergenic
rs74643788	16	17268972	C>A,G,T	0.05	intron_variant	XYLT1	5e-08	Tier 4: intronic/intergenic
rs12547243	8	130909710	A>G,T	0.05	splice_region_variant	ADCY8	2e-07	Tier 2: splice/UTR
rs35693284	18	74229912	G>A	0.05	intron_variant	RN7SL551P - CYB5A	2e-07	Tier 4: intronic/intergenic
rs1698919	18	77654787	G>A,C,T	0.05	intergenic_variant	BDP1P - RNA5SP461	4e-07	Tier 4: intronic/intergenic
rs56979833	15	30008518	A>G	0.05	intron_variant	NCAPGP2 - SYNGR2P1	4e-07	Tier 4: intronic/intergenic
rs12524310	6	67669441	T>C	0.05	intergenic_variant	Y_RNA - ERVH-3	9e-07	Tier 4: intronic/intergenic
rs1078793	7	45127042	T>A	0.05	intergenic_variant	TBRG4 - RAMP3	1e-06	Tier 4: intronic/intergenic
rs11017928	10	127409786	G>A,T	0.05	intron_variant	DOCK1	1e-06	Tier 4: intronic/intergenic
rs149640	14	72187545	G>A,C,T	0.05	intron_variant	RGS6	1e-06	Tier 4: intronic/intergenic
rs17567824	7	45593023	T>G	0.05	intron_variant	ADCY1	1e-06	Tier 4: intronic/intergenic
rs754118	20	50575367	T>A,C,G	0.05	intron_variant	PTPN1	1e-06	Tier 4: intronic/intergenic
rs6788567	3	112718200	A>C,T	0.05	intron_variant	MAT2AP1 - LINC02042	2e-06	Tier 4: intronic/intergenic
rs72737007	5	9972483	A>G	0.05	intergenic_variant	LINC02112 - ATPSCKMT	2e-06	Tier 4: intronic/intergenic
rs73262722	7	1277531	C>A,T	0.05	intergenic_variant	UNCX - MICALL2	2e-06	Tier 4: intronic/intergenic
rs7108263	11	134887988	C>G,T	0.05	intergenic_variant	LINC02714 - LINC02697	4e-06	Tier 4: intronic/intergenic
rs6891905	5	35670639	A>G	0.05	intron_variant	SPEF2	4e-06	Tier 4: intronic/intergenic
rs77093473	5	174306555	G>T	0.05	intergenic_variant	NSG2 - LINC01411	5e-06	Tier 4: intronic/intergenic
rs201158842	5	135769260	G>A,C,T	0.05	intron_variant	SLC25A48	5e-06	Tier 4: intronic/intergenic
rs78864163	3	18369916	G>A,T	0.05	intron_variant	SATB1, TBC1D5	6e-06	Tier 4: intronic/intergenic
rs3822095	4	89815366	T>A,C,G	0.05	intron_variant	SNCA	6e-06	Tier 4: intronic/intergenic
rs6736607	2	40207400	T>C	0.05	intron_variant	SLC8A1, SLC8A1-AS1	6e-06	Tier 4: intronic/intergenic
rs1426040	3	139978453	T>G	0.05	intron_variant	CLSTN2	7e-06	Tier 4: intronic/intergenic
rs61903333	11	59292111	T>C	0.05	intergenic_variant	RN7SL435P - OR5AN2P	7e-06	Tier 4: intronic/intergenic
rs6499854	16	56846930	T>A,C,G	0.05	3_prime_UTR_variant	NUP93	7e-06	Tier 2: splice/UTR
rs12451924	17	35497512	G>A	0.05	intron_variant	SLFN12L	7e-06	Tier 4: intronic/intergenic
rs11641605	16	60022652	A>G	0.05	intron_variant	LINC02141	7e-06	Tier 4: intronic/intergenic
rs841163	1	247747158	C>T	0.05	intron_variant	OR14A2	8e-06	Tier 4: intronic/intergenic
rs35396788	4	16240096	C>G,T	0.05	intron_variant	TAPT1-AS1	8e-06	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

255 likely benign, 166 pathogenic, 139 uncertain significance, 22 conflicting classifications of pathogenicity, 12 likely pathogenic, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11234	NM_004006.3(DMD):c.[10086+1G>T;10126del]		Pathogenic	no assertion criteria provided
1076228	NC_000023.10:g.(?27765013)(31697703_?)del	DCAF8L1	Pathogenic	criteria provided, single submitter
1062575	NC_000023.10:g.(?32613864)(32841514_?)dup	DMD	Pathogenic	criteria provided, single submitter
1066543	NM_004006.3(DMD):c.961-2A>G	DMD	Pathogenic	criteria provided, single submitter
1067593	NM_004006.3(DMD):c.9225-2A>T	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068606	NC_000023.10:g.(?_31462588)_31697713dup	DMD	Pathogenic	criteria provided, single submitter
1068684	NM_004006.3(DMD):c.1402_1406del (p.Glu468fs)	DMD	Pathogenic	criteria provided, single submitter
1069170	NC_000023.10:g.(?_31139940)_33229483del	DMD	Pathogenic	criteria provided, single submitter
1069343	NC_000023.10:g.(?31279052)(31279153_?)del	DMD	Pathogenic	criteria provided, single submitter
1069344	NC_000023.10:g.(?_32732288)_32834581del	DMD	Pathogenic	criteria provided, single submitter
1069345	NC_000023.10:g.(?32305637)(33357392_?)del	DMD	Pathogenic	criteria provided, single submitter
1069390	NM_004006.3(DMD):c.3426C>A (p.Cys1142Ter)	DMD	Pathogenic	criteria provided, single submitter
1069564	NC_000023.10:g.(?32328179)(32536268_?)del	DMD	Pathogenic	criteria provided, single submitter
1069565	NC_000023.10:g.(?32380895)(32519969_?)del	DMD	Pathogenic	criteria provided, single submitter
1069566	NC_000023.10:g.(?32827600)(33038327_?)del	DMD	Pathogenic	criteria provided, single submitter
1069567	NC_000023.10:g.(?32583809)(33038327_?)del	DMD	Pathogenic	criteria provided, single submitter
1069568	NC_000023.10:g.(?32456338)(32509655_?)del	DMD	Pathogenic	criteria provided, single submitter
1069569	NC_000023.10:g.(?32328189)(32503226_?)del	DMD	Pathogenic	criteria provided, single submitter
1069570	NC_000023.10:g.(?32479316)(32490436_?)del	DMD	Pathogenic	criteria provided, single submitter
1069704	NM_004006.3(DMD):c.418del (p.Leu140fs)	DMD	Pathogenic	criteria provided, single submitter
1069818	NM_004006.3(DMD):c.1383dup (p.Asp462Ter)	DMD	Pathogenic	criteria provided, single submitter
1069847	NC_000023.10:g.(?32429859)(32862987_?)del	DMD	Pathogenic	criteria provided, single submitter
1069848	NC_000023.10:g.(?32305636)(32361413_?)del	DMD	Pathogenic	criteria provided, single submitter
1069895	NM_004006.3(DMD):c.5404C>T (p.Gln1802Ter)	DMD	Pathogenic	criteria provided, single submitter
1069896	NM_004006.3(DMD):c.4777G>T (p.Glu1593Ter)	DMD	Pathogenic	criteria provided, single submitter
1069919	NM_004006.3(DMD):c.10000del (p.Tyr3334fs)	DMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069989	NM_004006.3(DMD):c.8853_8865del (p.Gln2952fs)	DMD	Pathogenic	criteria provided, single submitter
1070053	NM_004006.3(DMD):c.3511G>T (p.Glu1171Ter)	DMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1070054	NM_004006.3(DMD):c.2994T>A (p.Tyr998Ter)	DMD	Pathogenic	criteria provided, single submitter
1070271	NC_000023.10:g.(?31164402)(31697709_?)del	DMD	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 11 · 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
SNTA1	Orphanet:101016	Romano-Ward syndrome
PKP2	Orphanet:130	Brugada syndrome
PKP2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
PKP2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
PKP2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
PKP2	Orphanet:54260	Left ventricular noncompaction

Cohort genes → proteins

13 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	gencc,clinvar
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
UTRN	HGNC:12635	ENSG00000152818	P46939	Utrophin	clinvar
DDX53	HGNC:20083	ENSG00000184735	Q86TM3	Probable ATP-dependent RNA helicase DDX53	clinvar
TAB3-AS1	HGNC:20176	ENSG00000231542		TAB3 antisense RNA 1	clinvar
TASL	HGNC:25667	ENSG00000120280	Q9HAI6	TLR adapter interacting with SLC15A4 on the lysosome	clinvar
TAB3	HGNC:30681	ENSG00000157625	Q8N5C8	TGF-beta-activated kinase 1 and MAP3K7-binding protein 3	clinvar
DCAF8L1	HGNC:31810	ENSG00000226372	A6NGE4	DDB1- and CUL4-associated factor 8-like protein 1	clinvar
MIR548F5	HGNC:35309	ENSG00000221348		microRNA 548f-5	clinvar
MIR3915	HGNC:38955	ENSG00000263600		microRNA 3915	clinvar
FTHL17	HGNC:3987	ENSG00000132446	Q9BXU8	Ferritin heavy polypeptide-like 17	clinvar
MAGEB3	HGNC:6810	ENSG00000198798	O15480	Melanoma-associated antigen B3	clinvar
PKP2	HGNC:9024	ENSG00000057294	Q99959	Plakophilin-2	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.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
UTRN	Utrophin	May play a role in anchoring the cytoskeleton to the plasma membrane.
TASL	TLR adapter interacting with SLC15A4 on the lysosome	Innate immune adapter that mediates the recruitment and activation of IRF5 downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9.
TAB3	TGF-beta-activated kinase 1 and MAP3K7-binding protein 3	Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of ‘Lys-63’-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF).
PKP2	Plakophilin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 0 · Difficult: 5 · Unknown: 8 · 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
Scaffold/PPI	2	2.7×	0.303
Transcription factor	3	1.9×	0.303
Other/Unknown	8	1.1×	0.451

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
UTRN	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
DDX53	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, KH_dom
TAB3-AS1	Other/Unknown	no
TASL	Other/Unknown	no		TASL
TAB3	Transcription factor	no		Znf_RanBP2, CUE, Znf_RanBP2_sf
DCAF8L1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
MIR548F5	Other/Unknown	no
MIR3915	Other/Unknown	no
FTHL17	Other/Unknown	no		Ferritin, Ferritin_DPS_dom, Ferritin-like_diiron
MAGEB3	Other/Unknown	no		MHD_dom, MAGE_N, MAGE
PKP2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	4
broad (>20)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	5
calcaneal tendon	3
primordial germ cell in gonad	3
apex of heart	2
gastrocnemius	2
sural nerve	2
right testis	2
dorsal root ganglion	1
skeletal muscle tissue of rectus abdominis	1
trigeminal ganglion	1
hindlimb stylopod muscle	1
tendon	1
sperm	1
buccal mucosa cell	1
monocyte	1
mononuclear cell	1
epithelial cell of pancreas	1
germinal epithelium of ovary	1
pancreatic ductal cell	1
esophagogastric junction muscularis propria	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
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
UTRN	272	ubiquitous	marker	calcaneal tendon, tendon, sural nerve
DDX53	12	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, sperm
TAB3-AS1	109		yes	primordial germ cell in gonad, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
TASL	261	broad	marker	buccal mucosa cell, monocyte, mononuclear cell
TAB3	257	ubiquitous	yes	epithelial cell of pancreas, pancreatic ductal cell, germinal epithelium of ovary
DCAF8L1	7		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, right testis
MIR548F5	26		yes	calcaneal tendon, heart left ventricle, esophagogastric junction muscularis propria
MIR3915	45		yes	calcaneal tendon, stomach, gastrocnemius
FTHL17	11	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, oocyte, secondary oocyte
MAGEB3	13		marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
PKP2	237	ubiquitous	marker	heart right ventricle, apex of heart, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX53	2,965
DMD	2,479
PKP2	1,861
TAB3	1,853
UTRN	1,828
SNTA1	1,499
FTHL17	857
TASL	461
DCAF8L1	286
MAGEB3	212

Intra-cohort edges

A	B	Sources
DMD	SNTA1	biogrid_interaction, intact, string_interaction
DMD	UTRN	biogrid_interaction, string_interaction
FTHL17	MAGEB3	string_interaction
MAGEB3	TASL	string_interaction
SNTA1	UTRN	biogrid_interaction, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 5 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DMD	P11532	6
UTRN	P46939	3
DDX53	Q86TM3	2
TASL	Q9HAI6	2
PKP2	Q99959	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FTHL17	Q9BXU8	93.35
SNTA1	Q13424	80.00
MAGEB3	O15480	75.34
DCAF8L1	A6NGE4	74.03
TAB3	Q8N5C8	53.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 13 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the dystrophin-glycoprotein complex (DGC)	3	154.3×	4e-05	DMD, SNTA1, UTRN
Toll Like Receptor 7/8 (TLR7/8) Cascade	2	61.4×	0.009	TASL, TAB3
Toll Like Receptor 9 (TLR9) Cascade	2	58.6×	0.009	TASL, TAB3
Non-integrin membrane-ECM interactions	2	51.4×	0.009	DMD, SNTA1
Toll-like Receptor Cascades	2	41.4×	0.011	TASL, TAB3
SLC15A4:TASL-dependent IRF5 activation	1	317.2×	0.030	TASL
IRAK2 mediated activation of TAK1 complex	1	190.3×	0.037	TAB3
TICAM1,TRAF6-dependent induction of TAK1 complex	1	173.0×	0.037	TAB3
Alpha-protein kinase 1 signaling pathway	1	173.0×	0.037	TAB3
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	1	126.9×	0.043	TAB3
TRAF6-mediated induction of TAK1 complex within TLR4 complex	1	119.0×	0.043	TAB3
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	86.5×	0.052	TAB3
activated TAK1 mediates p38 MAPK activation	1	82.8×	0.052	TAB3
TNF signaling	1	70.5×	0.052	TAB3
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	61.4×	0.052	UTRN
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	59.5×	0.052	TAB3
TNFR1-induced NF-kappa-B signaling pathway	1	56.0×	0.052	TAB3
NOD1/2 Signaling Pathway	1	52.9×	0.052	TAB3
Striated Muscle Contraction	1	51.4×	0.052	DMD
MAP kinase activation	1	51.4×	0.052	TAB3
TAK1-dependent IKK and NF-kappa-B activation	1	50.1×	0.052	TAB3
Fc epsilon receptor (FCERI) signaling	1	45.3×	0.052	TAB3
Interleukin-1 family signaling	1	45.3×	0.052	TAB3
Innate Immune System	2	8.5×	0.052	TASL, TAB3
Interleukin-17 signaling	1	42.3×	0.053	TAB3
C-type lectin receptors (CLRs)	1	39.6×	0.054	TAB3
Toll Like Receptor 10 (TLR10) Cascade	1	35.9×	0.054	TAB3
Toll Like Receptor 5 (TLR5) Cascade	1	35.9×	0.054	TAB3
MyD88 cascade initiated on plasma membrane	1	34.0×	0.054	TAB3
Toll Like Receptor 3 (TLR3) Cascade	1	32.3×	0.054	TAB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 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 sodium ion transmembrane transport	3	395.0×	2e-06	DMD, SNTA1, UTRN
synaptic signaling	2	383.0×	3e-04	DMD, UTRN
ventricular cardiac muscle cell action potential	2	247.8×	5e-04	SNTA1, PKP2
regulation of heart rate	2	117.0×	0.002	DMD, SNTA1
regulation of muscle system process	1	2106.5×	0.004	DMD
regulation of cellular response to growth factor stimulus	1	2106.5×	0.004	DMD
maintenance of protein localization at cell tip	1	2106.5×	0.004	PKP2
muscle contraction	2	52.0×	0.005	SNTA1, UTRN
cardiac muscle cell action potential	1	1053.2×	0.006	DMD
muscle organ development	2	41.7×	0.006	DMD, UTRN
regulation of cell-substrate adhesion	1	702.2×	0.007	PKP2
positive regulation of toll-like receptor 8 signaling pathway	1	702.2×	0.007	TASL
regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	1	526.6×	0.008	DMD
peptide biosynthetic process	1	526.6×	0.008	DMD
positive regulation of toll-like receptor 7 signaling pathway	1	421.3×	0.009	TASL
maintenance of animal organ identity	1	421.3×	0.009	PKP2
regulation of substrate adhesion-dependent cell spreading	1	421.3×	0.009	PKP2
regulation of skeletal muscle contraction	1	351.1×	0.009	DMD
intermediate filament bundle assembly	1	351.1×	0.009	PKP2
desmosome assembly	1	300.9×	0.010	PKP2
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	300.9×	0.010	PKP2
desmosome organization	1	263.3×	0.010	PKP2
obsolete regulation of lysosomal lumen pH	1	263.3×	0.010	TASL
regulation of calcium ion transmembrane transport	1	263.3×	0.010	DMD
regulation of toll-like receptor signaling pathway	1	191.5×	0.013	TASL
cell communication by electrical coupling involved in cardiac conduction	1	175.5×	0.013	PKP2
regulation of ventricular cardiac muscle cell action potential	1	175.5×	0.013	PKP2
muscle cell development	1	117.0×	0.018	DMD
iron ion transport	1	110.9×	0.018	FTHL17
positive regulation of sodium ion transport	1	105.3×	0.018	PKP2

Therapeutics

Drugs indicated for this disease

8 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ataluren	Approved (phase 4)
Casimersen	Approved (phase 4)
Deflazacort	Approved (phase 4)
Delandistrogene Moxeparvovec	Approved (phase 4)
Eteplirsen	Approved (phase 4)
Golodirsen	Approved (phase 4)
Vamorolone	Approved (phase 4)
Viltolarsen	Approved (phase 4)
Creatine	Phase 3 (in late-stage trials)
Drisapersen	Phase 3 (in late-stage trials)
Edasalonexent	Phase 3 (in late-stage trials)
Eplerenone	Phase 3 (in late-stage trials)
Fordadistrogene Movaparvovec	Phase 3 (in late-stage trials)
Givinostat	Phase 3 (in late-stage trials)
Glutamine	Phase 3 (in late-stage trials)
Idebenone	Phase 3 (in late-stage trials)
Pamrevlumab	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Spironolactone	Phase 3 (in late-stage trials)
Tadalafil	Phase 3 (in late-stage trials)
Tamoxifen	Phase 3 (in late-stage trials)
Ubidecarenone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Epigalocatechin Gallate, Pemirolast, Prednisolone, Satralizumab, Sildenafil, Taldefgrobep Alfa.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 12

Druggability breadth: 3 of 13 evidence-associated genes (23%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UTRN	1	2
DMD	0	0
SNTA1	0	0
DDX53	0	0
TAB3-AS1	0	0
TASL	0	0
TAB3	0	0
DCAF8L1	0	0
MIR548F5	0	0
MIR3915	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EZUTROMID	2	UTRN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
UTRN	5	Binding:3, ADMET:2
TAB3	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
EZUTROMID	2	UTRN

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	1	UTRN
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	12	DMD, SNTA1, DDX53, TAB3-AS1, TASL, TAB3, DCAF8L1, MIR548F5, MIR3915, FTHL17 (+2 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DMD	0	UTRN
SNTA1	0	—
DDX53	0	—
TAB3-AS1	0	—
TASL	0	—
TAB3	1	—
DCAF8L1	0	—
MIR548F5	0	—
MIR3915	0	—
FTHL17	0	—
MAGEB3	0	—
PKP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 363.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	178
PHASE2	62
PHASE1/PHASE2	35
PHASE3	32
PHASE1	32
PHASE4	9
PHASE2/PHASE3	8
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04687020	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)
NCT05412394	PHASE4	RECRUITING	Once Weekly Infant Corticosteroid Trial for DMD
NCT06713135	PHASE4	ACTIVE_NOT_RECRUITING	A Study on Safety and Effectiveness of Long-term Treatment With Vamorolone in Boys With Duchenne Muscular Dystrophy
NCT07542314	PHASE4	NOT_YET_RECRUITING	Study to Evaluate the Safety and Effectiveness of ELEVIDYS in Participants With Duchenne Muscular Dystrophy Treated in a Post-Marketing Setting
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00819845	PHASE4	UNKNOWN	Ramipril Versus Carvedilol in Duchenne and Becker Patients
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT01999075	PHASE4	COMPLETED	Stacking Exercises Aid the Decline in FVC and Sick Time
NCT04708314	PHASE4	TERMINATED	An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
NCT03373968	PHASE2/PHASE3	RECRUITING	Givinostat in Duchenne’s Muscular Dystrophy Long-term Safety and Tolerability Study
NCT04281485	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
NCT04587908	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD）
NCT05195775	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Tadalafil as Adjuvant Therapy for DMD
NCT05693142	PHASE2/PHASE3	RECRUITING	AFFINITY DUCHENNE: RGX-202 Gene Therapy in Participants With Duchenne Muscular Dystrophy (DMD)
NCT05881408	PHASE3	ACTIVE_NOT_RECRUITING	A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
NCT05933057	PHASE3	RECRUITING	Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy
NCT05967351	PHASE3	ENROLLING_BY_INVITATION	A Long-term Follow-up Study of Participants Who Received Delandistrogene Moxeparvovec (SRP-9001) in a Previous Clinical Study
NCT07160634	PHASE3	RECRUITING	A Study of SGT-003 Gene Therapy in Ambulant Males With Duchenne Muscular Dystrophy (IMPACT DUCHENNE)
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT00004646	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy
NCT00110669	PHASE3	COMPLETED	High-dose Prednisone in Duchenne Muscular Dystrophy
NCT00308113	PHASE3	TERMINATED	CoQ10 and Prednisone in Non-Ambulatory DMD
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT01126697	PHASE2/PHASE3	COMPLETED	Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies
NCT01183767	PHASE2/PHASE3	COMPLETED	Sunphenon Epigallocatechin-Gallate (EGCg) in Duchenne Muscular Dystrophy
NCT01247207	PHASE3	COMPLETED	Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD)
NCT01557400	PHASE3	COMPLETED	Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
NCT01603407	PHASE3	COMPLETED	Finding the Optimum Regimen for Duchenne Muscular Dystrophy
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02255552	PHASE3	COMPLETED	Study of Eteplirsen in DMD Patients
NCT02354352	PHASE3	COMPLETED	Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
NCT02500381	PHASE3	COMPLETED	Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT02814019	PHASE3	TERMINATED	A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids
NCT02851797	PHASE3	COMPLETED	Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
NCT03039686	PHASE2/PHASE3	COMPLETED	Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy
NCT03354039	PHASE3	COMPLETED	Tamoxifen in Duchenne Muscular Dystrophy
NCT03532542	PHASE3	TERMINATED	An Extension Study to Evaluate Casimersen or Golodirsen in Patients With Duchenne Muscular Dystrophy
NCT03603288	PHASE3	TERMINATED	Phase III Study With Idebenone in Patients With Duchenne Muscular Dystrophy (SIDEROS-E)
NCT03642145	PHASE3	WITHDRAWN	A Study of Deflazacort (Emflaza®) in Participants With Duchenne Muscular Dystrophy (DMD)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATALUREN	4	10
ETEPLIRSEN	4	10
DELANDISTROGENE MOXEPARVOVEC	4	8
VAMOROLONE	4	8
VILTOLARSEN	4	8
GIVINOSTAT	4	6
GOLODIRSEN	4	6
CASIMERSEN	4	5
DEFLAZACORT	4	5
LISINOPRIL ANHYDROUS	4	4
IDEBENONE	4	3
CARVEDILOL	4	2
EPLERENONE	4	2
TAMOXIFEN	4	2
BISOPROLOL FUMARATE	4	1
CIANIDANOL	4	1
GENTAMICIN	4	1
IMLIFIDASE	4	1
ISOSORBIDE DINITRATE	4	1
NEBIVOLOL	4	1
RAMIPRIL	4	1
SATRALIZUMAB	4	1
SIROLIMUS	4	1
SPIRONOLACTONE	4	1
TADALAFIL	4	1
FORDADISTROGENE MOVAPARVOVEC	3	3
PAMREVLUMAB	3	3
ARGININE	3	2
UBIDECARENONE	3	2
DRISAPERSEN	3	1