Neuromuscular disease

Summary

Neuromuscular disease (MONDO:0019056) is a disease (an umbrella term covering 8 Mondo subtypes) caused by variants in RAPSN and TRPV4, with 50 cohort genes and 198 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (5 cohort genes). Top therapeutic interventions include ataluren, edaravone, and efgartigimod alfa.

At a glance

• Causal genes: RAPSN (GenCC Definitive), TRPV4 (GenCC Strong)
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 50
• ClinVar variants: 100
• Clinical trials: 198

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuromuscular disease
Mondo ID	MONDO:0019056
EFO	EFO:1001902
MeSH	D009468
Orphanet	68381
DOID	DOID:440
UMLS	C0027868
MedGen	10323
MedDRA	10029323
Is cancer (heuristic)	no

Also known as: nerve and muscle disorder · neuromuscular disease

Data availability: 100 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuromuscular disease

Related subtypes (71): congenital nervous system disorder, central nervous system disorder, autoimmune disorder of the nervous system, cranial nerve neuropathy, peripheral nervous system disorder, neuronitis, diplegia of upper limb, retinal disorder, developmental disability, restless legs syndrome, movement disorder, toxic encephalopathy, Barre-Lieou syndrome, Gerstmann syndrome, drug-induced akathisia, drug-induced dyskinesia, stiff-person syndrome, Worster-Drought syndrome, corneal-cerebellar syndrome, pachygyria-intellectual disability-epilepsy syndrome, porencephaly-cerebellar hypoplasia-internal malformations syndrome, symmetrical thalamic calcifications, neonatal brainstem dysfunction, primary orthostatic hypotension, rippling muscle disease with myasthenia gravis, periodic paralysis, qualitative or quantitative protein defects in neuromuscular diseases, specific learning disability, cerebellar hypoplasia-tapetoretinal degeneration syndrome, locked-in syndrome, dopa-responsive dystonia, idiopathic recurrent stupor, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, spontaneous periodic hypothermia, Sydenham chorea, duplication of the pituitary gland, Balint syndrome, paraneoplastic neurologic syndrome, persistent idiopathic facial pain, serotonin syndrome, hypothalamic adipsic hypernatraemia syndrome, exercise-induced malignant hyperthermia, perineural cyst, neuromyelitis optica, AL amyloidosis, AA amyloidosis, neuroleptic malignant syndrome, infectious disorder of the nervous system, central nervous system malformation, synaptopathy, nervous system neoplasm, sensory ganglionopathy, radiculitis, wet beriberi, perceptual disorders, prepubertal anorexia nervosa, neurocutaneous syndrome, neurovascular disorder, Wallerian degeneration, nervous system injury, neurosarcoidosis, neuroendocrine disorder, tubulinopathy, atactic disorder, hereditary neurological disease, meningitis-retention syndrome, KIF1A related neurological disorder, neurological pain disorder, neurodevelopmental disorder, post 5-alpha-reductase inhibitors treatment syndrome, post-selective serotonin reuptake inhibitor sexual dysfunction

Subtypes (8): akinetopsia, vestibular disorder, atrophic muscular disease, peripheral neuropathy, muscular channelopathy, neuromuscular junction disease, motor neuron disorder, hereditary neuromuscular disease

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

100 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 20 pathogenic/likely pathogenic, 16 pathogenic, 12 conflicting classifications of pathogenicity, 11 likely pathogenic, 2 benign/likely benign, 2 benign, 2 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
178839	NM_133378.4(TTN):c.[68689_68692delAACA;98315delG]		Pathogenic	criteria provided, single submitter
228243	NM_001100.4(ACTA1):c.808G>C (p.Gly270Arg)	ACTA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2582810	NM_001100.4(ACTA1):c.440C>T (p.Ser147Phe)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66402	NM_001927.4(DES):c.1360C>T (p.Arg454Trp)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66412	NM_001927.4(DES):c.35C>T (p.Ser12Phe)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
163403	NM_000117.3(EMD):c.266-2A>G	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
179133	NM_000117.3(EMD):c.650_654dup (p.Gln219fs)	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
179496	NM_000117.3(EMD):c.83-2A>G	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4728	NM_001368067.1(LDB3):c.494C>T (p.Ala165Val)	LDB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
48032	NM_170707.4(LMNA):c.1146C>T (p.Gly382=)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66853	NM_170707.4(LMNA):c.1608+1G>A	LMNA	Pathogenic	criteria provided, multiple submitters, no conflicts
48118	NM_000337.6(SGCD):c.390del (p.Ala131fs)	SGCD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929258	NM_003104.6(SORD):c.757del (p.Ala253fs)	SORD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126478	NM_021625.5(TRPV4):c.2396_2412del (p.Pro799fs)	TRPV4	Pathogenic	no assertion criteria provided
18434	NM_021625.5(TRPV4):c.832G>A (p.Glu278Lys)	TRPV4	Pathogenic	criteria provided, single submitter
18435	NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)	TRPV4	Pathogenic	criteria provided, multiple submitters, no conflicts
30469	NM_021625.5(TRPV4):c.1625C>A (p.Ser542Tyr)	TRPV4	Pathogenic	criteria provided, single submitter
30472	NM_021625.5(TRPV4):c.694C>T (p.Arg232Cys)	TRPV4	Pathogenic	criteria provided, multiple submitters, no conflicts
30473	NM_021625.5(TRPV4):c.947G>A (p.Arg316His)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30474	NM_021625.5(TRPV4):c.232G>T (p.Gly78Trp)	TRPV4	Pathogenic	no assertion criteria provided
30475	NM_021625.5(TRPV4):c.2219C>T (p.Thr740Ile)	TRPV4	Pathogenic	no assertion criteria provided
30476	NM_021625.5(TRPV4):c.826A>G (p.Lys276Glu)	TRPV4	Pathogenic	criteria provided, single submitter
39419	NM_021625.5(TRPV4):c.557G>A (p.Arg186Gln)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4993	NM_021625.5(TRPV4):c.1858G>A (p.Val620Ile)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4994	NM_021625.5(TRPV4):c.1781G>A (p.Arg594His)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4999	NM_021625.5(TRPV4):c.943C>T (p.Arg315Trp)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5000	NM_021625.5(TRPV4):c.806G>A (p.Arg269His)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5001	NM_021625.5(TRPV4):c.946C>T (p.Arg316Cys)	TRPV4	Pathogenic	criteria provided, multiple submitters, no conflicts
5002	NM_021625.5(TRPV4):c.805C>T (p.Arg269Cys)	TRPV4	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

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 29 · Orphanet: 139 · 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
RAPSN	Definitive	Autosomal recessive	neuromuscular disease	9
TRPV4	Strong	Autosomal dominant	neuromuscular disease	19
DCAF13	Limited	Autosomal recessive	neuromuscular disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV4	Orphanet:1216	Autosomal dominant congenital benign spinal muscular atrophy
TRPV4	Orphanet:263482	Spondyloepimetaphyseal dysplasia, Maroteaux type
TRPV4	Orphanet:2635	Metatropic dysplasia
TRPV4	Orphanet:431255	Scapuloperoneal spinal muscular atrophy
TRPV4	Orphanet:85169	Familial digital arthropathy-brachydactyly
TRPV4	Orphanet:86820	Familial avascular necrosis of femoral head
TRPV4	Orphanet:93304	Autosomal dominant brachyolmia
TRPV4	Orphanet:93314	Spondylometaphyseal dysplasia, Kozlowski type
TRPV4	Orphanet:99937	Autosomal dominant Charcot-Marie-Tooth disease type 2C
RAPSN	Orphanet:33108	Lethal multiple pterygium syndrome
RAPSN	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
RAPSN	Orphanet:994	Fetal akinesia deformation sequence
BCS1L	Orphanet:123	Björnstad syndrome
BCS1L	Orphanet:1460	Isolated complex III deficiency
BCS1L	Orphanet:254902	Renal tubulopathy-encephalopathy-liver failure syndrome
BCS1L	Orphanet:53693	GRACILE syndrome
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
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
SGCD	Orphanet:154	Familial isolated dilated cardiomyopathy
SGCD	Orphanet:219	Delta-sarcoglycan-related limb-girdle muscular dystrophy R6
SORD	Orphanet:700508	Distal muscle weakness-foot deformity-elevated sorbitol level-hereditary motor neuropathy
SPTAN1	Orphanet:697160	Infantile epileptic spasms syndrome
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

Cohort genes → proteins

50 cohort genes, 47 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	50

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPV4	HGNC:18083	ENSG00000111199	Q9HBA0	Transient receptor potential cation channel subfamily V member 4	gencc,clinvar
DCAF13	HGNC:24535	ENSG00000164934	Q9NV06	DDB1- and CUL4-associated factor 13	gencc
RAPSN	HGNC:9863	ENSG00000165917	Q13702	43 kDa receptor-associated protein of the synapse	gencc
BCS1L	HGNC:1020	ENSG00000074582	Q9Y276	Mitochondrial chaperone BCS1	clinvar
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
SCN4A	HGNC:10591	ENSG00000007314	P35499	Sodium channel protein type 4 subunit alpha	clinvar
SGCD	HGNC:10807	ENSG00000170624	Q92629	Delta-sarcoglycan	clinvar
SORD	HGNC:11184	ENSG00000140263	Q00796	Sorbitol dehydrogenase	clinvar
SPTAN1	HGNC:11273	ENSG00000197694	Q13813	Spectrin alpha chain, non-erythrocytic 1	clinvar
STIP1	HGNC:11387	ENSG00000168439	P31948	Stress-induced-phosphoprotein 1	clinvar
CELF3	HGNC:11967	ENSG00000159409	Q5SZQ8	CUGBP Elav-like family member 3	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	clinvar
TMEM184B	HGNC:1310	ENSG00000198792	Q9Y519	Transmembrane protein 184B	clinvar
CIAO1	HGNC:14280	ENSG00000144021	O76071	Probable cytosolic iron-sulfur protein assembly protein CIAO1	clinvar
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	clinvar
ACER3	HGNC:16066	ENSG00000078124	Q9NUN7	Alkaline ceramidase 3	clinvar
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	clinvar
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	clinvar
MTCH1	HGNC:17586	ENSG00000137409	Q9NZJ7	Mitochondrial carrier homolog 1	clinvar
TUBA1B	HGNC:18809	ENSG00000123416	P68363	Tubulin alpha-1B chain	clinvar
SMC3	HGNC:2468	ENSG00000108055	Q9UQE7	Structural maintenance of chromosomes protein 3	clinvar
TTC27	HGNC:25986	ENSG00000018699	Q6P3X3	Tetratricopeptide repeat protein 27	clinvar
MCTP1	HGNC:26183	ENSG00000175471	Q6DN14	Multiple C2 and transmembrane domain-containing protein 1	clinvar
AFAP1L1	HGNC:26714	ENSG00000157510	Q8TED9	Actin filament-associated protein 1-like 1	clinvar
DES	HGNC:2770	ENSG00000175084	P17661	Desmin	clinvar
TMEM106A	HGNC:28288	ENSG00000184988	Q96A25	Transmembrane protein 106A	clinvar
C1QTNF9	HGNC:28732	ENSG00000240654	P0C862	Complement C1q and tumor necrosis factor-related protein 9A	clinvar
CFAP74	HGNC:29368	ENSG00000142609	Q9C0B2	Cilia- and flagella-associated protein 74	clinvar
MSTO1	HGNC:29678	ENSG00000125459	Q9BUK6	Protein misato homolog 1	clinvar
NFASC	HGNC:29866	ENSG00000163531	O94856	Neurofascin	clinvar
VWA1	HGNC:30910	ENSG00000179403	Q6PCB0	von Willebrand factor A domain-containing protein 1	clinvar
EMD	HGNC:3331	ENSG00000102119	P50402	Emerin	clinvar
ABCA7	HGNC:37	ENSG00000064687	Q8IZY2	Phospholipid-transporting ATPase ABCA7	clinvar
GGPS1	HGNC:4249	ENSG00000152904	O95749	Geranylgeranyl pyrophosphate synthase	clinvar
TTN-AS1	HGNC:44124	ENSG00000237298		TTN antisense RNA 1	clinvar
GOLGA2	HGNC:4425	ENSG00000167110	Q08379	Golgin subfamily A member 2	clinvar
H6PD	HGNC:4795	ENSG00000049239	O95479	GDH/6PGL endoplasmic bifunctional protein	clinvar
HMGCR	HGNC:5006	ENSG00000113161	P04035	3-hydroxy-3-methylglutaryl-coenzyme A reductase	clinvar
HNRNPL	HGNC:5045	ENSG00000104824	P14866	Heterogeneous nuclear ribonucleoprotein L	clinvar
MYHAS	HGNC:50609	ENSG00000272975		myosin heavy chain gene cluster antisense RNA	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	clinvar
MT-TL1	HGNC:7490	ENSG00000209082		mitochondrially encoded tRNA-Leu (UUA/G) 1	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
MYH8	HGNC:7578	ENSG00000133020	P13535	Myosin-8	clinvar
MYO7B	HGNC:7607	ENSG00000169994	Q6PIF6	Unconventional myosin-VIIb	clinvar
ATP1A1	HGNC:799	ENSG00000163399	P05023	Sodium/potassium-transporting ATPase subunit alpha-1	clinvar
POLG	HGNC:9179	ENSG00000140521	P54098	DNA polymerase subunit gamma-1	clinvar
PSAP	HGNC:9498	ENSG00000197746	P07602	Prosaposin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV4	Transient receptor potential cation channel subfamily V member 4	Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity.
DCAF13	DDB1- and CUL4-associated factor 13	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
RAPSN	43 kDa receptor-associated protein of the synapse	Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.
BCS1L	Mitochondrial chaperone BCS1	Chaperone necessary for the incorporation of Rieske iron-sulfur protein UQCRFS1 into the mitochondrial respiratory chain complex III.
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.
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.
SGCD	Delta-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.
SORD	Sorbitol dehydrogenase	Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols.
SPTAN1	Spectrin alpha chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
STIP1	Stress-induced-phosphoprotein 1	Acts as a co-chaperone for HSP90AA1.
CELF3	CUGBP Elav-like family member 3	RNA-binding protein involved in the regulation of pre-mRNA alternative splicing.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
ACTA1	Actin, alpha skeletal muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
TMEM184B	Transmembrane protein 184B	May activate the MAP kinase signaling pathway.
CIAO1	Probable cytosolic iron-sulfur protein assembly protein CIAO1	Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins.
LDB3	LIM domain-binding protein 3	May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
ACER3	Alkaline ceramidase 3	Endoplasmic reticulum and Golgi ceramidase that catalyzes the hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-ceramides, dihydroceramides and phytoceramides into sphingoid bases like sphingosine and free fatty acids at alkali…
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.
MTCH1	Mitochondrial carrier homolog 1	Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane.
TUBA1B	Tubulin alpha-1B chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
SMC3	Structural maintenance of chromosomes protein 3	Central component of cohesin, a complex required for chromosome cohesion during the cell cycle.
MCTP1	Multiple C2 and transmembrane domain-containing protein 1	Calcium sensor which is essential for the stabilization of normal baseline neurotransmitter release and for the induction and long-term maintenance of presynaptic homeostatic plasticity.
AFAP1L1	Actin filament-associated protein 1-like 1	May be involved in podosome and invadosome formation.
DES	Desmin	Muscle-specific type III intermediate filament essential for proper muscular structure and function.
TMEM106A	Transmembrane protein 106A	Activates macrophages and polarizes them into M1-like macrophages through the activation of the MAPK and NF-kappaB signaling pathway.
C1QTNF9	Complement C1q and tumor necrosis factor-related protein 9A	Probable adipokine.
CFAP74	Cilia- and flagella-associated protein 74	As part of the central apparatus of the cilium axoneme may play a role in cilium movement.
MSTO1	Protein misato homolog 1	Involved in the regulation of mitochondrial distribution and morphology.
NFASC	Neurofascin	Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions.
VWA1	von Willebrand factor A domain-containing protein 1	Promotes matrix assembly.
EMD	Emerin	Stabilizes and promotes the formation of a nuclear actin cortical network.
ABCA7	Phospholipid-transporting ATPase ABCA7	Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.
GGPS1	Geranylgeranyl pyrophosphate synthase	Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
GOLGA2	Golgin subfamily A member 2	Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane.
H6PD	GDH/6PGL endoplasmic bifunctional protein	Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power an…
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.
HNRNPL	Heterogeneous nuclear ribonucleoprotein L	Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion.
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.
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
MYH8	Myosin-8	Muscle contraction.
MYO7B	Unconventional myosin-VIIb	Myosins are actin-based motor molecules with ATPase activity.
ATP1A1	Sodium/potassium-transporting ATPase subunit alpha-1	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.
POLG	DNA polymerase subunit gamma-1	Catalytic subunit of DNA polymerase gamma solely responsible for replication of mitochondrial DNA (mtDNA).
PSAP	Prosaposin	Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46).

Protein-family classification

Druggable: 12 · Difficult: 11 · Unknown: 27 · Druggable fraction: 0.24

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	6.7×	0.041
Scaffold/PPI	8	2.8×	0.041
Antibody/Immunoglobulin	3	1.8×	0.653
Transporter	1	1.6×	0.877
Other/Unknown	27	1.0×	0.877
Enzyme (other)	4	1.0×	0.877
Kinase	1	0.6×	0.951
Transcription factor	3	0.5×	0.951

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV4	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4
DCAF13	Scaffold/PPI	no		WD40_rpt, Sof1, WD40/YVTN_repeat-like_dom_sf
RAPSN	Transcription factor	no		Postsynaptic, Znf_RING, TPR-like_helical_dom_sf
BCS1L	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
SCN4A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a4su_mammal
SGCD	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
SORD	Enzyme (other)	yes	1.1.1.14	ADH_Zn_CS, GroES-like_sf, ADH-like_C
SPTAN1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
STIP1	Other/Unknown	no		STI1_HS-bd, TPR-like_helical_dom_sf, TPR_2
CELF3	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, CELF3/4/5/6_RRM1
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
ACTA1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
TMEM184B	Other/Unknown	no		Ostalpha/TMEM184C
CIAO1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
ACER3	Enzyme (other)	yes	3.5.1.23	ACER
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain
MTCH1	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf
TUBA1B	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
SMC3	Other/Unknown	no		RecF/RecN/SMC_N, SMC_hinge, SMC
TTC27	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC27/Emw1
MCTP1	Other/Unknown	no		C2_dom, MCTP_C, C2_domain_sf
AFAP1L1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, AFAP
DES	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
TMEM106A	Other/Unknown	no		TMEM106, TMEM106_C, TMEM106_N
C1QTNF9	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
CFAP74	Antibody/Immunoglobulin	yes		Ig-like_fold, Ig-CFAP74_2nd, Ig-CFAP74_3rd
MSTO1	Other/Unknown	no		Misato_II_tubulin-like, DML1/Misato_tubulin, Tubulin/FtsZ_GTPase_sf
NFASC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
VWA1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Ig-like_fold
EMD	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, LEM_emerin
ABCA7	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
GGPS1	Enzyme (other)	yes	2.5.1.29	Polyprenyl_synt, Isoprenoid_synthase_dom_sf, Polyprenyl_synt_CS
TTN-AS1	Other/Unknown	no
GOLGA2	Other/Unknown	no		GOLGA, GOLGA_C, GOLGA_cons_dom
H6PD	Other/Unknown	no		G6P_DH, 6-phosphogluconolactonase_DevB, Glc/Gal-6P_isomerase
HMGCR	Enzyme (other)	yes	1.1.1.34	SSD, HMG_CoA_Rdtase, HMG_CoA_Rdtase_eu_arc
HNRNPL	Other/Unknown	no		RRM_dom, HnRNP-L/PTB, Nucleotide-bd_a/b_plait_sf
MYHAS	Other/Unknown	no
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
MT-TL1	Other/Unknown	no
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
MYH8	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYO7B	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom
ATP1A1	Transcription factor	no	7.2.2.3	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
POLG	Other/Unknown	no		DNA-dir_DNA_pol_A_palm_dom, DNA-dir_DNA_pol_A_mt, RNaseH-like_sf
PSAP	Other/Unknown	no		SAP_A, SapB_1, SapB_2

Expression context

Cohort genes with no expression data: 0.

48 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)	50
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	10
apex of heart	6
gastrocnemius	5
skeletal muscle tissue of rectus abdominis	5
skeletal muscle tissue of biceps brachii	5
cortical plate	4
ventricular zone	4
gluteal muscle	3
ganglionic eminence	3
oocyte	2
primordial germ cell in gonad	2
secondary oocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
left lobe of thyroid gland	2
right lobe of thyroid gland	2
right hemisphere of cerebellum	2
adrenal tissue	2
left testis	2
biceps brachii	2
C1 segment of cervical spinal cord	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV4	171	ubiquitous	marker	cartilage tissue, lower esophagus mucosa, olfactory segment of nasal mucosa
DCAF13	266	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
RAPSN	159	tissue_specific	marker	hindlimb stylopod muscle, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius
BCS1L	279	ubiquitous	marker	body of pancreas, metanephros cortex, apex of heart
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
SCN4A	153	tissue_specific	yes	hindlimb stylopod muscle, gastrocnemius, skeletal muscle tissue of rectus abdominis
SGCD	247	broad	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, heart right ventricle
SORD	199	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
SPTAN1	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
STIP1	294	ubiquitous	marker	adrenal tissue, left testis, ganglionic eminence
CELF3	177	broad	marker	cortical plate, right hemisphere of cerebellum, ganglionic eminence
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
ACTA1	203	broad	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm
TMEM184B	293	ubiquitous	marker	C1 segment of cervical spinal cord, right frontal lobe, spinal cord
CIAO1	284	ubiquitous	marker	right adrenal gland cortex, left adrenal gland cortex, left adrenal gland
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
ACER3	252	ubiquitous	marker	endothelial cell, inferior vagus X ganglion, ileal mucosa
ACTN2	226	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus
MTCH1	288	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
TUBA1B	153	ubiquitous	marker	ventricular zone, superior frontal gyrus, frontal pole
SMC3	276	ubiquitous	marker	tendon of biceps brachii, ventricular zone, oocyte
TTC27	246	ubiquitous	marker	primordial germ cell in gonad, calcaneal tendon, colonic epithelium
MCTP1	245	ubiquitous	marker	secondary oocyte, monocyte, mononuclear cell
AFAP1L1	205	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, heart left ventricle
DES	280	broad	marker	apex of heart, saphenous vein, gastrocnemius
TMEM106A	228	ubiquitous	marker	buccal mucosa cell, renal medulla, pylorus
C1QTNF9	137	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, apex of heart, hindlimb stylopod muscle
CFAP74	163	tissue_specific	marker	right uterine tube, epithelium of bronchus, bronchial epithelial cell
MSTO1	134	tissue_specific	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPL	7,376
LMNA	7,173
GOLGA2	5,697
H6PD	5,473
STIP1	5,243
HMGCR	5,062
SMC3	5,056
TTN	4,237
SORD	3,915
BCS1L	3,789

Intra-cohort edges

A	B	Sources
ACTN2	LDB3	biogrid_interaction, intact, string_interaction
ACTN2	MYH7	biogrid_interaction, string_interaction
ACTN2	MYH8	biogrid_interaction
ACTN2	TTN	string_interaction
ATP1A1	MTCH1	biogrid_interaction
C1QTNF9	TTN	intact
EMD	LMNA	intact, string_interaction
GGPS1	HMGCR	string_interaction
H6PD	SORD	string_interaction
LDB3	MYH7	string_interaction
LDB3	TTN	string_interaction
LMNA	SGCD	string_interaction
MYH7	SPTAN1	biogrid_interaction
MYH7	TTN	string_interaction
RYR1	TTN	intact

Structural data

PDB: 32 · AlphaFold-only: 15 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
MYH7	P12883	43
TUBA1B	P68363	39
POLG	P54098	36
LMNA	P02545	28
HMGCR	P04035	24
PSAP	P07602	20
TRPV4	Q9HBA0	19
ACTN2	P35609	16
ATP1A1	P05023	13
SMC3	Q9UQE7	12
GGPS1	O95749	9
STIP1	P31948	8
SPTAN1	Q13813	7
LRP1	Q07954	7
EMD	P50402	6
ABCA7	Q8IZY2	6
ACTA1	P68133	5
GOLGA2	Q08379	4
DCAF13	Q9NV06	3
SCN4A	P35499	3
SORD	Q00796	3
HNRNPL	P14866	3
MYO7B	Q6PIF6	3
RYR1	P21817	2
LDB3	O75112	2
ACER3	Q9NUN7	2
NFASC	O94856	2
CELF3	Q5SZQ8	1
CIAO1	O76071	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RAPSN	Q13702	93.29
TTC27	Q6P3X3	90.66
BCS1L	Q9Y276	87.10
MSTO1	Q9BUK6	83.83
SGCD	Q92629	81.43
VWA1	Q6PCB0	79.26
DES	P17661	77.73
MTCH1	Q9NZJ7	76.29
TMEM106A	Q96A25	76.10
MYH8	P13535	75.13
TMEM184B	Q9Y519	73.63
CFAP74	Q9C0B2	69.38
MCTP1	Q6DN14	65.61
C1QTNF9	P0C862	65.61
AFAP1L1	Q8TED9	64.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 209. Enrichment computed across 50 evidence-associated genes (32 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 32 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	5	48.2×	1e-05	TTN, ACTA1, ACTN2, DES, MYH8
Muscle contraction	6	14.5×	3e-04	RYR1, SCN4A, ACTA1, ACTN2, MYH8, ATP1A1
Interaction between L1 and Ankyrins	3	34.5×	0.006	SCN4A, SPTAN1, NFASC
Depolymerization of the Nuclear Lamina	2	47.6×	0.033	EMD, LMNA
Lanosterol biosynthesis	2	47.6×	0.033	GGPS1, HMGCR
Initiation of Nuclear Envelope (NE) Reformation	2	37.6×	0.044	EMD, LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	2	32.4×	0.049	GOLGA2, LMNA
Nephrin family interactions	2	29.7×	0.049	SPTAN1, ACTN2
Nuclear Envelope Breakdown	2	28.6×	0.049	EMD, LMNA
L1CAM interactions	3	11.3×	0.049	SCN4A, SPTAN1, TUBA1B
COPI-mediated anterograde transport	3	10.3×	0.054	SPTAN1, TUBA1B, GOLGA2
Cardiac conduction	3	10.2×	0.054	RYR1, SCN4A, ATP1A1
Formation of the dystrophin-glycoprotein complex (DGC)	2	19.3×	0.077	SGCD, ACTA1
Platelet degranulation	3	8.2×	0.084	TTN, ACTN2, PSAP
Activation of gene expression by SREBF (SREBP)	2	16.2×	0.091	GGPS1, HMGCR
Assembly and cell surface presentation of NMDA receptors	2	15.9×	0.091	ACTN2, TUBA1B
Breakdown of the nuclear lamina	1	119.0×	0.103	LMNA
Fructose biosynthesis	1	89.2×	0.112	SORD
Post NMDA receptor activation events	2	12.8×	0.112	ACTN2, TUBA1B
Ion homeostasis	2	12.8×	0.112	RYR1, ATP1A1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	2	12.1×	0.112	STIP1, TUBA1B
Hemostasis	4	4.5×	0.112	ACTN2, KIF1B, TUBA1B, PSAP
Activation of NMDA receptors and postsynaptic events	2	11.5×	0.113	ACTN2, TUBA1B
Vesicle-mediated transport	4	4.3×	0.113	SPTAN1, KIF1B, TUBA1B, LRP1
Kinesins	2	11.2×	0.115	KIF1B, TUBA1B
Formation of xylulose-5-phosphate	1	59.5×	0.120	SORD
Sphingolipid metabolism	2	10.5×	0.120	ACER3, PSAP
Response to elevated platelet cytosolic Ca2+	2	10.2×	0.120	ACTN2, PSAP
RHO GTPase cycle	3	5.6×	0.120	SPTAN1, STIP1, TUBA1B
Non-integrin membrane-ECM interactions	2	9.7×	0.126	SGCD, ACTA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 43 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle contraction	8	38.7×	9e-09	RYR1, SCN4A, TTN, ACTA1, DES, EMD, MYH7, MYH8
positive regulation of striated muscle contraction	2	391.9×	0.001	TRPV4, ATP1A1
muscle filament sliding	3	73.5×	0.001	TTN, MYH7, MYH8
striated muscle contraction	3	58.8×	0.002	RYR1, TTN, MYH7
cardiac muscle cell development	3	43.5×	0.003	SGCD, TTN, ACTN2
skeletal muscle contraction	3	35.6×	0.005	TTN, MYH7, MYH8
skeletal muscle thin filament assembly	2	130.6×	0.005	TTN, ACTA1
amyloid-beta clearance by cellular catabolic process	2	98.0×	0.007	ABCA7, LRP1
positive regulation of amyloid-beta clearance	2	98.0×	0.007	ABCA7, LRP1
sarcomere organization	3	26.7×	0.007	TTN, LDB3, ACTN2
isoprenoid biosynthetic process	2	78.4×	0.010	GGPS1, HMGCR
osmosensory signaling pathway	2	71.3×	0.011	TRPV4, ATP1A1
regulation of the force of heart contraction	2	46.1×	0.022	MYH7, ATP1A1
nuclear envelope organization	2	46.1×	0.022	DES, LMNA
negative regulation of endocytosis	2	43.5×	0.023	MCTP1, ABCA7
negative regulation of glucocorticoid biosynthetic process	1	391.9×	0.031	ATP1A1
geranylgeranyl diphosphate biosynthetic process	1	391.9×	0.031	GGPS1
hyperosmotic salinity response	1	391.9×	0.031	TRPV4
actin filament uncapping	1	391.9×	0.031	ACTN2
phytosphingosine biosynthetic process	1	391.9×	0.031	ACER3
blood vessel endothelial cell delamination	1	391.9×	0.031	TRPV4
regulation of skeletal muscle contraction by action potential	1	391.9×	0.031	SCN4A
regulation of postsynaptic membrane organization	1	391.9×	0.031	RAPSN
establishment of protein localization to postsynaptic membrane	1	391.9×	0.031	RAPSN
positive regulation of transcytosis	1	391.9×	0.031	LRP1
ganglioside GM1 transport to membrane	1	391.9×	0.031	PSAP
lysosomal transport	2	32.7×	0.031	LRP1, PSAP
cardiac muscle cell action potential involved in contraction	2	32.7×	0.031	SCN4A, ATP1A1
positive regulation of cholesterol efflux	2	29.0×	0.031	ABCA7, LRP1
muscle organ development	3	11.6×	0.031	SGCD, EMD, LMNA

Therapeutics

Drugs indicated or in trials for this disease

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

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

Drug	Highest phase
Vitamin E	Phase 2

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 10 · Phased (≥1): 12 · Undrugged: 38

Druggability breadth: 22 of 50 evidence-associated genes (44%) 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
SCN4A	CARBAMAZEPINE
SORD	EPALRESTAT
TUBA1B	COLCHICINE
GGPS1	MINODRONIC ACID
HMGCR	SIMVASTATIN
LMNA	BEPRIDIL
ATP1A1	DIGOXIN
POLG	ADEFOVIR DIPIVOXIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
SCN4A	24	4
TUBA1B	21	4
HMGCR	15	4
TRPV4	6	3
ATP1A1	5	4
GGPS1	4	4
SORD	2	4
SPTAN1	1	2
SMC3	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CARBAMAZEPINE	4	LMNA, SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	LMNA, SCN4A
LIDOCAINE	4	LMNA, SCN4A
IMIPRAMINE	4	LMNA, SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	LMNA, SCN4A
NIFEDIPINE	4	LMNA, SCN4A
DILTIAZEM	4	LMNA, SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	LMNA, SCN4A
EPALRESTAT	4	LMNA, SORD
COLCHICINE	4	LMNA, TUBA1B
VINBLASTINE	4	TUBA1B
LEVOFLOXACIN ANHYDROUS	4	TUBA1B
DOCETAXEL	4	TUBA1B
NOSCAPINE	4	TUBA1B
VINBLASTINE SULFATE	4	LMNA, TUBA1B
PACLITAXEL	4	LMNA, TUBA1B
LEVOFLOXACIN	4	TUBA1B
VINORELBINE	4	TUBA1B
TIRBANIBULIN	4	TUBA1B
PODOFILOX	4	LMNA, TUBA1B
VINCRISTINE	4	LMNA, TUBA1B
DOCETAXEL ANHYDROUS	4	TUBA1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
TUBA1B	1,689	Binding:1648, Functional:35, ADMET:6
HMGCR	153	Binding:148, Functional:5
GGPS1	129	Binding:128, ADMET:1
TRPV4	99	Binding:94, Functional:5
SCN4A	95	Binding:69, Functional:18, ADMET:7, Toxicity:1
ATP1A1	50	Binding:50
POLG	33	Binding:30, ADMET:2, Functional:1
SORD	17	Binding:16, Functional:1
RYR1	16	Binding:13, Functional:3
STIP1	13	Binding:13
LMNA	12	Binding:9, Functional:3
PSAP	12	Binding:8, ADMET:4
SPTAN1	7	Binding:7
SMC3	7	Binding:7
HNRNPL	7	Binding:7
RAPSN	1	Binding:1
TTN	1	Binding:1
KIF1B	1	Binding:1
EMD	1	Binding:1
GOLGA2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SORD	1.1.1.14	L-iditol 2-dehydrogenase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
ACER3	3.5.1.23	ceramidase
GGPS1	2.5.1.29	geranylgeranyl diphosphate synthase
HMGCR	1.1.1.34	hydroxymethylglutaryl-CoA reductase (NADPH)
ATP1A1	7.2.2.3	P-type Na+ transporter

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBA1B	1,689
GGPS1	129
HMGCR	153

Pharmacogenomics

Cohort genes with a PharmGKB record: 48; 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

29 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)
CARBAMAZEPINE	4	LMNA, SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
LIDOCAINE	4	LMNA, SCN4A
IMIPRAMINE	4	LMNA, SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	LMNA, SCN4A
NIFEDIPINE	4	LMNA, SCN4A
DILTIAZEM	4	LMNA, SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	LMNA, SCN4A
EPALRESTAT	4	LMNA, SORD
COLCHICINE	4	LMNA, TUBA1B
VINBLASTINE	4	TUBA1B
LEVOFLOXACIN ANHYDROUS	4	TUBA1B
DOCETAXEL	4	TUBA1B
NOSCAPINE	4	TUBA1B
VINBLASTINE SULFATE	4	LMNA, TUBA1B
PACLITAXEL	4	LMNA, TUBA1B
LEVOFLOXACIN	4	TUBA1B
VINORELBINE	4	TUBA1B
TIRBANIBULIN	4	TUBA1B
PODOFILOX	4	LMNA, TUBA1B
VINCRISTINE	4	LMNA, TUBA1B
DOCETAXEL ANHYDROUS	4	TUBA1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	SCN4A, SORD, TUBA1B, GGPS1, HMGCR, LMNA, ATP1A1, POLG
B	Phased (≥1) drug, not yet approved	4	TRPV4, SPTAN1, SMC3, PSAP
C	Druggable family + PDB, no drug	5	RYR1, TTN, ACER3, NFASC, ABCA7
D	Druggable family + AlphaFold only, no drug	2	CFAP74, VWA1
E	Difficult family or no structure, no drug	31	DCAF13, RAPSN, BCS1L, SGCD, STIP1, CELF3, ACTA1, TMEM184B, CIAO1, LDB3 (+21 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EMD	1	LMNA
DCAF13	0	—
RAPSN	1	—
BCS1L	0	—
RYR1	16	—
SGCD	0	—
STIP1	13	—
CELF3	0	—
TTN	1	—
ACTA1	0	—
TMEM184B	0	—
CIAO1	0	—
LDB3	0	—
ACER3	0	—
ACTN2	0	—
KIF1B	1	—
MTCH1	0	—
TTC27	0	—
MCTP1	0	—
AFAP1L1	0	—
DES	0	—
TMEM106A	0	—
C1QTNF9	0	—
CFAP74	0	—
MSTO1	0	—
NFASC	0	—
VWA1	0	—
ABCA7	0	—
TTN-AS1	0	—
GOLGA2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 198.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	164
PHASE3	13
PHASE2	10
PHASE1	6
PHASE4	2
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	PHASE4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	PHASE3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	PHASE3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	PHASE3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	PHASE3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT03272802	PHASE2/PHASE3	UNKNOWN	Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT06339580	PHASE2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00860951	PHASE1/PHASE2	COMPLETED	P300 Brain Computer Interface Keyboard to Operate Assistive Technology
NCT01074359	PHASE2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	PHASE2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	PHASE2	TERMINATED	Evaluation of Vital Capacity
NCT02362425	PHASE1/PHASE2	COMPLETED	Antioxidant Therapy in RYR1-Related Congenital Myopathy
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT00252252	PHASE1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation
NCT01560741	PHASE1	UNKNOWN	Telemedicine and Ventilator Titration in Chronic Respiratory Patients Initiating Non-invasive Ventilation
NCT01621984	PHASE1	COMPLETED	Therapeutic Riding and Neuromuscular Disease
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT03440034	PHASE1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT01900132	Not specified	RECRUITING	Electrical Impedance Myography: Natural History Studies inNeuromuscular Disorders and Healthy Volunteers
NCT02253290	Not specified	RECRUITING	Neuropsychological and Psychosocial Follow up of Children and Adolescents With Neuromuscular Disease
NCT02851043	Not specified	RECRUITING	Non-Invasive Respiratory Monitor
NCT03355105	Not specified	ACTIVE_NOT_RECRUITING	Comparison of Two Methods of Adjusting the Mechanical In-Exsuflation in Neuromuscular Adult Patients
NCT03478566	Not specified	ACTIVE_NOT_RECRUITING	Transcutaneous CO2 Monitoring at Home for Children With Neuromuscular Disease
NCT03797183	Not specified	RECRUITING	Genesis Electrical Impedance Tomography (EIT): A Preliminary Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATALUREN	4	3
EDARAVONE	4	1
EFGARTIGIMOD ALFA	4	1
FIBRINOGEN I 125	4	1
RILUZOLE	4	1
APITEGROMAB	3	3
TALDEFGROBEP ALFA	3	1
TELITACICEPT	3	1
DELPACIBART ZOTADIRSEN	2	1
DERAMIOCEL	2	1
NEXIGURAN	2	1
SEVASEMTEN	2	1
ZICLUMERAN	2	1
CHEMBL5435500	0	1