Limb-girdle muscular dystrophy

Summary

Limb-girdle muscular dystrophy (MONDO:0016971) is a disease with 36 cohort genes and 39 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (4 cohort genes). Top therapeutic interventions include lisinopril anhydrous, deflazacort, and bidridistrogene xeboparvovec.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 36
• ClinVar variants: 101
• Clinical trials: 39

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.32	Worldwide	Validated
Lifetime Prevalence	1-9 / 100 000	5.7	Egypt	Validated
Point prevalence	1-9 / 1 000 000	0.81	Netherlands	Validated
Point prevalence	1-9 / 100 000	2.27	United Kingdom	Validated
Point prevalence	1-9 / 100 000	1.55	Japan	Validated
Point prevalence	1-9 / 100 000	6.9	Spain	Validated
Point prevalence	1-9 / 100 000	1.1	Ireland	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	limb-girdle muscular dystrophy
Mondo ID	MONDO:0016971
MeSH	D049288
Orphanet	263
DOID	DOID:11724
ICD-11	887807212
NCIT	C84828
SNOMED CT	78468005
UMLS	C0686353
MedGen	151940
GARD	0006907
Is cancer (heuristic)	no

Also known as: Leyden-Mobius muscular dystrophy · LGMD · limb-girdle muscular dystrophy

Data availability: 101 ClinVar variants · 4 ClinGen variant curations · 3 cell lines.

Disease family

An umbrella term covering 3 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 › limb-girdle muscular dystrophy

Related subtypes (12): 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, childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome, oculopharyngodistal myopathy

Subtypes (3): muscular dystrophy, limb-girdle, autosomal dominant, autosomal recessive limb-girdle muscular dystrophy, POMGNT2-related limb-girdle muscular dystrophy R24

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

101 retrieved; paginated sample, class counts are floors:

45 conflicting classifications of pathogenicity, 26 uncertain significance, 11 pathogenic/likely pathogenic, 7 benign/likely benign, 7 pathogenic, 3 likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
498076	NM_012210.4(TRIM32):c.691del (p.Ala231fs)	ASTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180773	NM_000070.3(CAPN3):c.661G>T (p.Gly221Cys)	CAPN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282173	NM_000070.3(CAPN3):c.1303G>A (p.Glu435Lys)	CAPN3	Pathogenic	reviewed by expert panel
210752	NM_004369.4(COL6A3):c.6181C>T (p.Arg2061Ter)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4846734	GRCh38/hg38 Xp21.1(chrX:32505641-32996904)x1	DMD	Pathogenic	criteria provided, single submitter
7280	NM_001005361.3(DNM2):c.1105C>T (p.Arg369Trp)	DNM2	Pathogenic	reviewed by expert panel
4067072	NM_001130987.2(DYSF):c.5643-1G>A	DYSF	Pathogenic	reviewed by expert panel
94303	NM_001130987.2(DYSF):c.3381_3382del (p.Phe1128fs)	DYSF	Pathogenic	reviewed by expert panel
4221	NM_024301.5(FKRP):c.826C>A (p.Leu276Ile)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60540	NM_021971.4(GMPPB):c.1000G>A (p.Asp334Asn)	GMPPB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803007	NM_000859.3(HMGCR):c.2465G>A (p.Gly822Asp)	HMGCR	Pathogenic	criteria provided, single submitter
626314	NM_001199563.2(POPDC1):c.262C>T (p.Arg88Ter)	POPDC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9437	NM_000023.4(SGCA):c.229C>T (p.Arg77Cys)	SGCA	Pathogenic	reviewed by expert panel
42035	NM_000232.5(SGCB):c.341C>T (p.Ser114Phe)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1033986	NM_021942.6(TRAPPC11):c.518_521del (p.Phe173fs)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
474342	NM_021942.6(TRAPPC11):c.1192C>T (p.Arg398Ter)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
202529	NM_001267550.2(TTN):c.107635C>T (p.Gln35879Ter)	TTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374145	NM_001267550.2(TTN):c.103360del (p.Glu34454fs)	TTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16829	NM_001927.4(DES):c.1154T>C (p.Leu385Pro)	DES	Likely pathogenic	criteria provided, single submitter
429219	NM_170707.4(LMNA):c.1126T>C (p.Tyr376His)	LMNA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4072122	NM_000540.3(RYR1):c.14789T>G (p.Leu4930Trp)	RYR1	Likely pathogenic	criteria provided, single submitter
195705	NM_213599.3(ANO5):c.2521C>G (p.His841Asp)	ANO5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
977163	NM_213599.3(ANO5):c.395A>T (p.Lys132Met)	ANO5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8279	NM_033337.2(CAV3):c.216C>G (p.Cys72Trp)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283039	NM_001849.4(COL6A2):c.446G>A (p.Arg149His)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93927	NM_001849.4(COL6A2):c.1970-3C>A	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1477625	NM_004369.4(COL6A3):c.3733G>A (p.Gly1245Arg)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283049	NM_004369.4(COL6A3):c.2180A>C (p.Tyr727Ser)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288387	NM_004369.4(COL6A3):c.7114G>A (p.Asp2372Asn)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639334	NM_004369.4(COL6A3):c.2144C>T (p.Ser715Leu)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 160 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome
SCN11A	Orphanet:306577	Hereditary sodium channelopathy-related small fibers neuropathy
SCN11A	Orphanet:391392	Familial episodic pain syndrome with predominantly lower limb involvement
SCN11A	Orphanet:391397	Hereditary sensory and autonomic neuropathy type 7
SCN11A	Orphanet:46348	Paroxysmal extreme pain disorder
SCN11A	Orphanet:88642	Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN11A	Orphanet:90026	Primary erythromelalgia
SCN4A	Orphanet:681	Hypokalemic periodic paralysis
SCN4A	Orphanet:682	Hyperkalemic periodic paralysis
SCN4A	Orphanet:684	Paramyotonia congenita of Von Eulenburg
SCN4A	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
SCN4A	Orphanet:99734	Myotonia fluctuans
SCN4A	Orphanet:99735	Myotonia permanens
SCN4A	Orphanet:99736	Acetazolamide-responsive myotonia
SGCA	Orphanet:62	Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3
SGCB	Orphanet:119	Beta-sarcoglycan-related limb-girdle muscular dystrophy R4
POPDC1	Orphanet:476084	BVES-related limb-girdle muscular dystrophy
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
CAPN3	Orphanet:267	Calpain-3-related limb-girdle muscular dystrophy R1
CAPN3	Orphanet:565909	Calpain-3-related limb-girdle muscular dystrophy D4
CAV3	Orphanet:101016	Romano-Ward syndrome
CAV3	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
CAV3	Orphanet:488650	Distal myopathy, Tateyama type
CAV3	Orphanet:97238	Rippling muscle disease
SYNE1	Orphanet:319332	Autosomal recessive myogenic arthrogryposis multiplex congenita
SYNE1	Orphanet:88644	Autosomal recessive ataxia, Beauce type
SYNE1	Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy

Cohort genes → proteins

36 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	36

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
SCN11A	HGNC:10583	ENSG00000168356	Q9UI33	Sodium channel protein type 11 subunit alpha	clinvar
SCN4A	HGNC:10591	ENSG00000007314	P35499	Sodium channel protein type 4 subunit alpha	clinvar
SGCA	HGNC:10805	ENSG00000108823	Q16586	Alpha-sarcoglycan	clinvar
SGCB	HGNC:10806	ENSG00000163069	Q16585	Beta-sarcoglycan	clinvar
POPDC1	HGNC:1152	ENSG00000112276	Q8NE79	Popeye domain-containing protein 1	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	clinvar
ASTN2	HGNC:17021	ENSG00000148219	O75129	Astrotactin-2	clinvar
SYNE1	HGNC:17089	ENSG00000131018	Q8NF91	Nesprin-1	clinvar
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	clinvar
MYO18B	HGNC:18150	ENSG00000133454	Q8IUG5	Unconventional myosin-XVIIIb	clinvar
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	clinvar
COL6A2	HGNC:2212	ENSG00000142173	P12110	Collagen alpha-2(VI) chain	clinvar
COL6A3	HGNC:2213	ENSG00000163359	P12111	Collagen alpha-3(VI) chain	clinvar
GMPPB	HGNC:22932	ENSG00000173540	Q9Y5P6	Mannose-1-phosphate guanylyltransferase catalytic subunit beta	clinvar
TRAPPC11	HGNC:25751	ENSG00000168538	Q7Z392	Trafficking protein particle complex subunit 11	clinvar
ANO5	HGNC:27337	ENSG00000171714	Q75V66	Anoctamin-5	clinvar
DES	HGNC:2770	ENSG00000175084	P17661	Desmin	clinvar
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	clinvar
EPG5	HGNC:29331	ENSG00000152223	Q9HCE0	Ectopic P granules protein 5 homolog	clinvar
DNM2	HGNC:2974	ENSG00000079805	P50570	Dynamin-2	clinvar
DNMT1	HGNC:2976	ENSG00000130816	P26358	DNA (cytosine-5)-methyltransferase 1	clinvar
DYSF	HGNC:3097	ENSG00000135636	O75923	Dysferlin	clinvar
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	clinvar
TTN-AS1	HGNC:44124	ENSG00000237298		TTN antisense RNA 1	clinvar
SETX	HGNC:445	ENSG00000107290	Q7Z333	Helicase senataxin	clinvar
HMGCR	HGNC:5006	ENSG00000113161	P04035	3-hydroxy-3-methylglutaryl-coenzyme A reductase	clinvar
LAMA2	HGNC:6482	ENSG00000196569	P24043	Laminin subunit alpha-2	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
MYH2	HGNC:7572	ENSG00000125414	Q9UKX2	Myosin-2	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
NEB	HGNC:7720	ENSG00000183091	P20929	Nebulin	clinvar
PLEC	HGNC:9069	ENSG00000178209	Q15149	Plectin	clinvar
POLG	HGNC:9179	ENSG00000140521	P54098	DNA polymerase subunit gamma-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
SCN11A	Sodium channel protein type 11 subunit alpha	Sodium channel mediating the voltage-dependent sodium ion permeability of excitable membranes.
SCN4A	Sodium channel protein type 4 subunit alpha	Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SGCA	Alpha-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
SGCB	Beta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
POPDC1	Popeye domain-containing protein 1	Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.
CAV3	Caveolin-3	May act as a scaffolding protein within caveolar membranes.
ASTN2	Astrotactin-2	Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.
SYNE1	Nesprin-1	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
FKRP	Ribitol 5-phosphate transferase FKRP	Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phos…
MYO18B	Unconventional myosin-XVIIIb	May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes.
POMGNT1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins.
COL6A2	Collagen alpha-2(VI) chain	Collagen VI acts as a cell-binding protein.
COL6A3	Collagen alpha-3(VI) chain	Collagen VI acts as a cell-binding protein.
GMPPB	Mannose-1-phosphate guanylyltransferase catalytic subunit beta	Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex.
TRAPPC11	Trafficking protein particle complex subunit 11	Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
ANO5	Anoctamin-5	Plays a role in plasma membrane repair in a process involving annexins.
DES	Desmin	Muscle-specific type III intermediate filament essential for proper muscular structure and function.
DMD	Dystrophin	Anchors the extracellular matrix to the cytoskeleton via F-actin.
EPG5	Ectopic P granules protein 5 homolog	Involved in autophagy.
DNM2	Dynamin-2	Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton.
DNMT1	DNA (cytosine-5)-methyltransferase 1	DNA methyltransferase that methylates CpG residues.
DYSF	Dysferlin	Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
SETX	Helicase senataxin	ATP-dependent 5’->3’ DNA/RNA helicase that preferentially unwinds RNA substrates over DNA, playing a crucial role in resolving R-loops and promoting transcription termination.
HMGCR	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis.
LAMA2	Laminin subunit alpha-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LMNA	Prelamin-A/C	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
MYH2	Myosin-2	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
NEB	Nebulin	This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils.
PLEC	Plectin	Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.
POLG	DNA polymerase subunit gamma-1	Catalytic subunit of DNA polymerase gamma solely responsible for replication of mitochondrial DNA (mtDNA).

Protein-family classification

Druggable: 11 · Difficult: 7 · Unknown: 18 · Druggable fraction: 0.31

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
Ion channel	3	9.3×	0.037
Scaffold/PPI	5	2.4×	0.246
Complement	1	7.4×	0.378
Antibody/Immunoglobulin	2	1.6×	0.789
Protease	1	1.0×	0.910
Enzyme (other)	3	1.0×	0.910
Other/Unknown	18	0.9×	0.910
Kinase	1	0.8×	0.910
Transcription factor	2	0.5×	0.943

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
SCN11A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
SCN4A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a4su_mammal
SGCA	Other/Unknown	no		Cadg, Sarcoglycan_alpha/epsilon, Cadherin-like_sf
SGCB	Other/Unknown	no		Sarcoglycan, Sgcb
POPDC1	Other/Unknown	no		POPDC1-3, RmlC-like_jellyroll, cNMP-bd_dom_sf
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS
ASTN2	Complement	yes		MACPF, Astrotactin, FN3_sf
SYNE1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N
MYO18B	Other/Unknown	no		Myosin_head_motor_dom-like, P-loop_NTPase, MYSc_Myo18
POMGNT1	Enzyme (other)	yes	2.4.1.312	Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like
COL6A2	Other/Unknown	no		VWF_A, Collagen, vWFA_dom_sf
COL6A3	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom
GMPPB	Enzyme (other)	yes	2.7.7.13	NTP_transferase_dom, Hexapep_transf_CS, Nucleotide-diphossugar_trans
TRAPPC11	Other/Unknown	no		TPC11, TRAPPC11_C
ANO5	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
DES	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
EPG5	Other/Unknown	no		Autophagy-related_EPG5, TPR_Epg5, TPR_Epg5_mid
DNM2	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
DNMT1	Transcription factor	no	2.1.1.37	BAH_dom, C5_MeTfrase, Znf_CXXC
DYSF	Other/Unknown	no		C2_dom, Peroxin/Ferlin, Ferlin_A-domain
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
TTN-AS1	Other/Unknown	no
SETX	Other/Unknown	no		P-loop_NTPase, DNA2/NAM7_AAA_11, DNA2/NAM7-like_C
HMGCR	Enzyme (other)	yes	1.1.1.34	SSD, HMG_CoA_Rdtase, HMG_CoA_Rdtase_eu_arc
LAMA2	Other/Unknown	no		Laminin_IV, EGF, Laminin_G
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYH2	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
NEB	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulin-like
PLEC	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
POLG	Other/Unknown	no		DNA-dir_DNA_pol_A_palm_dom, DNA-dir_DNA_pol_A_mt, RNaseH-like_sf

Expression context

Cohort genes with no expression data: 0.

33 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)	0
broad (>20)	36
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	12
gastrocnemius	7
skeletal muscle tissue of rectus abdominis	5
apex of heart	5
skeletal muscle tissue of biceps brachii	4
calcaneal tendon	4
gluteal muscle	3
buccal mucosa cell	3
dorsal root ganglion	3
cardiac muscle of right atrium	3
left ventricle myocardium	3
tibialis anterior	3
biceps brachii	3
C1 segment of cervical spinal cord	2
vastus lateralis	2
trigeminal ganglion	2
adenohypophysis	2
stromal cell of endometrium	2
mucosa of transverse colon	2
adrenal tissue	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
SCN11A	166	broad	marker	buccal mucosa cell, dorsal root ganglion, male germ line stem cell (sensu Vertebrata) in testis
SCN4A	153	tissue_specific	yes	hindlimb stylopod muscle, gastrocnemius, skeletal muscle tissue of rectus abdominis
SGCA	190	broad	marker	hindlimb stylopod muscle, gastrocnemius, apex of heart
SGCB	288	ubiquitous	marker	tendon of biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
POPDC1	211	ubiquitous	yes	left ventricle myocardium, tibialis anterior, cardiac muscle of right atrium
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord
CAV3	157	tissue_specific	yes	hindlimb stylopod muscle, vastus lateralis, triceps brachii
ASTN2	236	ubiquitous	marker	buccal mucosa cell, trigeminal ganglion, dorsal root ganglion
SYNE1	275	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, calcaneal tendon
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle
MYO18B	148	broad	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle
POMGNT1	269	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, adenohypophysis
COL6A2	263	ubiquitous	marker	stromal cell of endometrium, right coronary artery, descending thoracic aorta
COL6A3	264	broad	marker	stromal cell of endometrium, visceral pleura, skin of hip
GMPPB	172	ubiquitous	marker	body of pancreas, adenohypophysis, mucosa of transverse colon
TRAPPC11	277	ubiquitous	marker	calcaneal tendon, adrenal tissue, primordial germ cell in gonad
ANO5	220	broad	marker	cardiac muscle of right atrium, left ventricle myocardium, vastus lateralis
DES	280	broad	marker	apex of heart, saphenous vein, gastrocnemius
DMD	295	ubiquitous	marker	trigeminal ganglion, skeletal muscle tissue of rectus abdominis, dorsal root ganglion
EPG5	260	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, bone marrow cell
DNM2	234	ubiquitous	marker	metanephros cortex, granulocyte, mucosa of transverse colon
DNMT1	266	ubiquitous	marker	oocyte, secondary oocyte, sural nerve
DYSF	257	ubiquitous	marker	blood, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
TTN-AS1	174	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, right atrium auricular region
SETX	281	ubiquitous	marker	right testis, calcaneal tendon, left testis
HMGCR	286	ubiquitous	marker	adrenal tissue, ventricular zone, cortical plate
LAMA2	272	ubiquitous	marker	mucosa of stomach, calcaneal tendon, right ovary

Protein interactions among cohort

Intra-cohort edges: 55.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNMT1	7,179
LMNA	7,173
HMGCR	5,062
DNM2	4,715
TTN	4,237
PLEC	3,529
POLG	3,400
FLNC	3,174
SETX	3,127
SYNE1	2,886

Intra-cohort edges

A	B	Sources
ANO5	DYSF	string_interaction
ANO5	FKRP	string_interaction
ANO5	POMGNT1	string_interaction
ANO5	SGCA	string_interaction
ANO5	SGCB	string_interaction
CAPN3	CAV3	string_interaction
CAPN3	DMD	string_interaction
CAPN3	DYSF	string_interaction
CAPN3	FKRP	string_interaction
CAPN3	FLNC	biogrid_interaction, string_interaction
CAPN3	SGCB	string_interaction
CAPN3	TTN	biogrid_interaction, intact, string_interaction
CAV3	DMD	string_interaction
CAV3	DYSF	string_interaction
CAV3	POPDC1	string_interaction
COL6A2	COL6A3	string_interaction
COL6A2	DMD	string_interaction
COL6A3	DYSF	intact
DES	DMD	string_interaction
DES	DYSF	biogrid_interaction, intact
DES	PLEC	string_interaction
DMD	DYSF	string_interaction
DMD	FLNC	string_interaction
DMD	LAMA2	string_interaction
DMD	NEB	string_interaction
DMD	PLEC	string_interaction
DMD	POPDC1	string_interaction
DMD	SGCA	string_interaction
DMD	SGCB	string_interaction
DYSF	FKRP	string_interaction
DYSF	FLNC	intact
DYSF	LAMA2	string_interaction
DYSF	NEB	biogrid_interaction, intact
DYSF	POPDC1	string_interaction
DYSF	SGCA	string_interaction
DYSF	SGCB	string_interaction
DYSF	TTN	biogrid_interaction, intact
FKRP	GMPPB	string_interaction
FKRP	LAMA2	string_interaction
FKRP	POMGNT1	string_interaction
FKRP	SGCA	string_interaction
FKRP	SGCB	string_interaction
GMPPB	POMGNT1	string_interaction
GMPPB	TRAPPC11	string_interaction
LAMA2	SGCA	string_interaction
LMNA	SYNE1	string_interaction
MYH2	TTN	string_interaction
MYH7	TTN	string_interaction
MYO18B	PLEC	intact
NEB	TTN	intact, string_interaction

Structural data

PDB: 24 · AlphaFold-only: 11 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
MYH7	P12883	43
POLG	P54098	36
LMNA	P02545	28
DNMT1	P26358	27
HMGCR	P04035	24
FLNC	Q14315	14
PLEC	Q15149	14
DYSF	O75923	11
POMGNT1	Q8WZA1	10
FKRP	Q9H9S5	8
COL6A3	P12111	6
DMD	P11532	6
CAPN3	P20807	5
SCN4A	P35499	3
ASTN2	O75129	3
SYNE1	Q8NF91	3
GMPPB	Q9Y5P6	3
NEB	P20929	3
RYR1	P21817	2
LAMA2	P24043	2
COL6A2	P12110	1
EPG5	Q9HCE0	1
DNM2	P50570	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CAV3	P56539	88.54
TRAPPC11	Q7Z392	87.76
ANO5	Q75V66	82.22
SGCA	Q16586	80.15
DES	P17661	77.73
SGCB	Q16585	76.67
POPDC1	Q8NE79	76.08
MYH2	Q9UKX2	73.51
SCN11A	Q9UI33	69.66
MYO18B	Q8IUG5	60.66
SETX	Q7Z333	52.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 102. Enrichment computed across 36 evidence-associated genes (29 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 29 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	4	42.6×	1e-04	TTN, DES, DMD, NEB
Formation of the dystrophin-glycoprotein complex (DGC)	4	42.6×	1e-04	SGCA, SGCB, DMD, LAMA2
Non-integrin membrane-ECM interactions	4	21.3×	9e-04	SGCA, SGCB, DMD, LAMA2
Muscle contraction	5	13.3×	9e-04	RYR1, SCN11A, SCN4A, CAV3, NEB
Assembly of collagen fibrils and other multimeric structures	3	20.7×	0.008	COL6A2, COL6A3, PLEC
Matriglycan biosynthesis on DAG1	2	56.3×	0.009	FKRP, POMGNT1
ECM proteoglycans	3	15.5×	0.013	COL6A2, COL6A3, LAMA2
Extracellular matrix organization	4	8.7×	0.014	SGCA, SGCB, CAPN3, LAMA2
Interaction between L1 and Ankyrins	2	25.4×	0.026	SCN11A, SCN4A
EGR2 and SOX10-mediated initiation of Schwann cell myelination	2	25.4×	0.026	HMGCR, LAMA2
Cardiac conduction	3	11.2×	0.026	RYR1, SCN11A, SCN4A
Phase 0 - rapid depolarisation	2	23.9×	0.027	SCN11A, SCN4A
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	196.9×	0.036	POMGNT1
Smooth Muscle Contraction	2	18.3×	0.036	CAV3, DYSF
Collagen chain trimerization	2	17.9×	0.036	COL6A2, COL6A3
Signaling by PDGF	2	17.5×	0.036	COL6A2, COL6A3
NCAM1 interactions	2	17.1×	0.036	COL6A2, COL6A3
Breakdown of the nuclear lamina	1	131.3×	0.043	LMNA
DAG1 core M1 glycosylations	1	98.5×	0.054	POMGNT1
NOSTRIN mediated eNOS trafficking	1	78.8×	0.056	DNM2
DAG1 core M2 glycosylations	1	78.8×	0.056	POMGNT1
Collagen degradation	2	12.1×	0.056	COL6A2, COL6A3
Collagen biosynthesis and modifying enzymes	2	11.8×	0.056	COL6A2, COL6A3
Synthesis of GDP-mannose	1	65.6×	0.064	GMPPB
Meiotic synapsis	2	9.7×	0.073	SYNE1, LMNA
Stimuli-sensing channels	2	9.4×	0.074	RYR1, ANO5
Integrin cell surface interactions	2	9.3×	0.074	COL6A2, COL6A3
L1CAM interactions	2	8.3×	0.088	SCN11A, SCN4A
Strand-asynchronous mitochondrial DNA replication	1	39.4×	0.088	POLG
Formation of annular gap junctions	1	35.8×	0.088	DNM2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 35 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle organ development	10	47.7×	2e-12	SGCA, SGCB, POPDC1, CAPN3, CAV3, COL6A3, DMD, LAMA2 (+2 more)
muscle contraction	8	47.5×	9e-10	RYR1, SCN4A, SGCA, TTN, FKRP, DES, MYH2, MYH7
cardiac muscle cell development	5	89.2×	3e-07	SGCB, TTN, CAV3, MYO18B, PLEC
regulation of heart rate	4	53.5×	9e-05	POPDC1, CAV3, DMD, MYH7
sarcomere organization	4	43.8×	2e-04	TTN, CAPN3, FLNC, PLEC
muscle filament sliding	3	90.3×	3e-04	TTN, MYH2, MYH7
striated muscle contraction	3	72.2×	5e-04	RYR1, TTN, MYH7
regulation of skeletal muscle contraction	2	160.5×	0.003	CAV3, DMD
localization of cell	2	160.5×	0.003	FKRP, POMGNT1
detection of muscle stretch	2	137.6×	0.003	TTN, CAV3
cardiac muscle contraction	3	34.4×	0.003	TTN, DMD, MYH7
skeletal muscle organ development	2	120.4×	0.004	SCN11A, DES
cardiac muscle hypertrophy	2	96.3×	0.006	TTN, CAV3
negative regulation of protein localization to cell surface	2	74.1×	0.009	CAV3, ASTN2
response to glucose	3	21.9×	0.009	SGCB, COL6A2, COL6A3
intracellular protein localization	4	12.0×	0.009	CAV3, DMD, LMNA, PLEC
regulation of sodium ion transmembrane transport	2	60.2×	0.012	CAV3, DMD
nuclear envelope organization	2	56.6×	0.013	DES, LMNA
protein O-linked glycosylation via mannose	2	53.5×	0.013	FKRP, POMGNT1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	18.1×	0.013	FKRP, COL6A2, COL6A3
neuron apoptotic process	3	15.9×	0.017	COL6A2, COL6A3, EPG5
gene expression	4	9.1×	0.017	SGCB, POMGNT1, EPG5, PLEC
monocyte activation involved in immune response	1	481.5×	0.018	DYSF
nucleotide transport	1	481.5×	0.018	EPG5
pentitol metabolic process	1	481.5×	0.018	FKRP
filtration diaphragm assembly	1	481.5×	0.018	FKRP
regulation of signal transduction by receptor internalization	1	481.5×	0.018	CAV3
epigenetic programming of gene expression	1	481.5×	0.018	DNMT1
protein-containing complex organization	1	481.5×	0.018	PLEC
regulation of nerve growth factor receptor activity	1	481.5×	0.018	CAV3

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

2 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Bidridistrogene Xeboparvovec	Phase 3
Deflazacort	Phase 3

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 30

Druggability breadth: 17 of 36 evidence-associated genes (47%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN11A	IMIPRAMINE
SCN4A	CARBAMAZEPINE
DNMT1	DECITABINE
HMGCR	SIMVASTATIN
LMNA	BEPRIDIL
POLG	ADEFOVIR DIPIVOXIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
SCN4A	24	4
SCN11A	15	4
HMGCR	15	4
DNMT1	6	4
POLG	1	4
RYR1	0	0
SGCA	0	0
SGCB	0	0
POPDC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	LMNA, SCN11A, SCN4A
SERTINDOLE	4	SCN11A, SCN4A
PIMOZIDE	4	LMNA, SCN11A, SCN4A
NIFEDIPINE	4	LMNA, SCN11A, SCN4A
DILTIAZEM	4	LMNA, SCN11A, SCN4A
MIBEFRADIL	4	SCN11A, SCN4A
HALOPERIDOL	4	SCN11A, SCN4A
MEXILETINE	4	SCN11A, SCN4A
AMITRIPTYLINE	4	SCN11A, SCN4A
AMIODARONE	4	SCN11A, SCN4A
CHLORPROMAZINE	4	LMNA, SCN11A, SCN4A
CARBAMAZEPINE	4	LMNA, SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	LMNA, SCN4A
LIDOCAINE	4	LMNA, SCN4A
DECITABINE	4	DNMT1
AZACITIDINE	4	DNMT1, LMNA
CEPHALOTHIN	4	DNMT1
SIMVASTATIN	4	HMGCR
PRAVASTATIN	4	HMGCR
PITAVASTATIN CALCIUM	4	HMGCR
CERIVASTATIN	4	HMGCR
ATORVASTATIN	4	HMGCR
ROSUVASTATIN	4	HMGCR
CISAPRIDE	4	HMGCR
FLUVASTATIN	4	HMGCR
LOVASTATIN	4	HMGCR, LMNA
TANNIC ACID	4	HMGCR
PRAVASTATIN SODIUM	4	HMGCR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
DNMT1	233	Binding:229, Functional:3, ADMET:1
HMGCR	153	Binding:148, Functional:5
SCN4A	95	Binding:69, Functional:18, ADMET:7, Toxicity:1
SCN11A	33	Functional:16, Binding:15, ADMET:2
POLG	33	Binding:30, ADMET:2, Functional:1
RYR1	16	Binding:13, Functional:3
DNM2	15	Binding:15
LMNA	12	Binding:9, Functional:3
PLEC	12	Binding:12
TTN	1	Binding:1
POMGNT1	1	Binding:1
MYH2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase
GMPPB	2.7.7.13	mannose-1-phosphate guanylyltransferase
DNM2	3.6.5.5	dynamin GTPase
DNMT1	2.1.1.37	DNA (cytosine-5-)-methyltransferase
HMGCR	1.1.1.34	hydroxymethylglutaryl-CoA reductase (NADPH)

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DNMT1	233
HMGCR	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 35; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1
HMGCR	1

Chemical tractability of cohort targets

30 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)
IMIPRAMINE	4	LMNA, SCN11A, SCN4A
SERTINDOLE	4	SCN11A, SCN4A
PIMOZIDE	4	LMNA, SCN11A, SCN4A
NIFEDIPINE	4	LMNA, SCN11A, SCN4A
DILTIAZEM	4	LMNA, SCN11A, SCN4A
MIBEFRADIL	4	SCN11A, SCN4A
HALOPERIDOL	4	SCN11A, SCN4A
MEXILETINE	4	SCN11A, SCN4A
AMITRIPTYLINE	4	SCN11A, SCN4A
AMIODARONE	4	SCN11A, SCN4A
CHLORPROMAZINE	4	LMNA, SCN11A, SCN4A
CARBAMAZEPINE	4	LMNA, SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	LMNA, SCN4A
LIDOCAINE	4	LMNA, SCN4A
DECITABINE	4	DNMT1
AZACITIDINE	4	DNMT1, LMNA
CEPHALOTHIN	4	DNMT1
SIMVASTATIN	4	HMGCR
PRAVASTATIN	4	HMGCR
PITAVASTATIN CALCIUM	4	HMGCR
CERIVASTATIN	4	HMGCR
ATORVASTATIN	4	HMGCR
ROSUVASTATIN	4	HMGCR
CISAPRIDE	4	HMGCR
FLUVASTATIN	4	HMGCR
LOVASTATIN	4	HMGCR, LMNA
TANNIC ACID	4	HMGCR
PRAVASTATIN SODIUM	4	HMGCR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	SCN11A, SCN4A, DNMT1, HMGCR, LMNA, POLG
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	8	RYR1, TTN, CAPN3, ASTN2, POMGNT1, COL6A3, GMPPB, FLNC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	22	SGCA, SGCB, POPDC1, CAV3, SYNE1, FKRP, MYO18B, COL6A2, TRAPPC11, ANO5 (+12 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SYNE1	0	LMNA
RYR1	16	—
SGCA	0	—
SGCB	0	—
POPDC1	0	—
TTN	1	—
CAPN3	0	—
CAV3	0	—
ASTN2	0	—
FKRP	0	—
MYO18B	0	—
POMGNT1	1	—
COL6A2	0	—
COL6A3	0	—
GMPPB	0	—
TRAPPC11	0	—
ANO5	0	—
DES	0	—
DMD	0	—
EPG5	0	—
DNM2	15	—
DYSF	0	—
FLNC	0	—
TTN-AS1	0	—
SETX	0	—
LAMA2	0	—
MYH2	1	—
MYH7	0	—
NEB	0	—
PLEC	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 39.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	23
PHASE1	7
PHASE1/PHASE2	5
PHASE3	2
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06246513	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
NCT01126697	PHASE2/PHASE3	COMPLETED	Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies
NCT03783923	PHASE3	TERMINATED	A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
NCT05230459	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
NCT00104078	PHASE1/PHASE2	COMPLETED	Study Evaluating MYO-029 in Adult Muscular Dystrophy
NCT02579239	PHASE1/PHASE2	COMPLETED	Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02836418	PHASE1/PHASE2	COMPLETED	Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT04054375	PHASE2	COMPLETED	Weekly Steroids in Muscular Dystrophy
NCT05588401	PHASE1/PHASE2	UNKNOWN	Evaluating Safety and Efficacy of Autologous Gene-edited Muscle Stem Cells (GenPHSats-bASKet)
NCT05876780	PHASE1	ACTIVE_NOT_RECRUITING	A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01344798	PHASE1	COMPLETED	Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
NCT02050776	PHASE1	WITHDRAWN	Stem Cell Therapy in Limb Girdle Muscular Dystrophy
NCT02245711	PHASE1	WITHDRAWN	Cell Therapy in Limb Girdle Muscular Dystrophy
NCT05906251	PHASE1	TERMINATED	A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/R2 (LGMD2B/R2, Dysferlin [DYSF] Related)
NCT06747273	PHASE1	TERMINATED	Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Participants in the United States
NCT00390104	Not specified	RECRUITING	Molecular Analysis of Patients With Neuromuscular Disease
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT04475926	Not specified	ACTIVE_NOT_RECRUITING	A Study of the Natural History of Participants With LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, and LGMD2A/R1 ≥ 4 Years of Age, Who Are Managed in Routine Clinical Practice
NCT04989751	Not specified	ENROLLING_BY_INVITATION	A Multicenter Phenotype-Genotype Analysis of LGMD Patients in China
NCT05102799	Not specified	RECRUITING	MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants
NCT05206617	Not specified	ACTIVE_NOT_RECRUITING	3 Year Follow up on ANO5 Patients
NCT05618080	Not specified	RECRUITING	LGMD R1 Natural History Study
NCT06363357	Not specified	RECRUITING	The Effect of a Muscle-mimicking, Fabric-type Shoulder Orthosis on Functional Movements of the Upper Limb in Patients With Neuromuscular Disorder
NCT06390566	Not specified	ACTIVE_NOT_RECRUITING	Evolution of the Functional and Muscular State of Patients With Muscular Dystrophy 2A Belts
NCT06399770	Not specified	NOT_YET_RECRUITING	The Role of Muscle Ultrasound in Assessment of Sample of Patients With Limb-girdle Muscular Dystrophy
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.
NCT00457912	Not specified	COMPLETED	Genetic Characterization of Individuals With Limb Girdle Muscular Dystrophy
NCT01066455	Not specified	COMPLETED	Cardiac Outcome Measures in Children With Muscular Dystrophy
NCT01081080	Not specified	COMPLETED	Cardiac Magnetic Resonance in Children With Muscular Dystrophy
NCT02635321	Not specified	COMPLETED	MRI and Muscle Involvement in Patients With Mutations in GMPPB
NCT02759302	Not specified	COMPLETED	MRI on Persons With Mutations in POMT2 Gene (LGMD2N)
NCT03930628	Not specified	UNKNOWN	Limb-Girdle Muscular Dystrophy Type 2I in Norway
NCT03981289	Not specified	COMPLETED	Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry
NCT04202627	Not specified	COMPLETED	Biomarker Development in LGMD2i
NCT04772027	Not specified	UNKNOWN	Motor Parameters in Patients With Limb Girdle Muscular Dystrophy
NCT05409079	Not specified	UNKNOWN	Schulze Muscular Dystrophy Ability Clinical Study
NCT06378203	Not specified	UNKNOWN	Rehabilitation in Muscular Dystrophies From the Hospital Facility to the Home: Pilot Project [RIMUDI]

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LISINOPRIL ANHYDROUS	4	2
DEFLAZACORT	4	1
BIDRIDISTROGENE XEBOPARVOVEC	3	2
UBIDECARENONE	3	1
STAMULUMAB	2	1
ATYR-1940	1	2