Myopathy

Summary

Myopathy (MONDO:0005336) is a disease (an umbrella term covering 32 Mondo subtypes) caused by MYBPC1 (GenCC Strong), with 75 cohort genes (47 GWAS associations across 15 studies) and 46 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (7 cohort genes). Top therapeutic interventions include atorvastatin, prednisolone, and ubidecarenone.

At a glance

• Causal gene: MYBPC1 (GenCC Strong)
• Umbrella term: 32 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 47
• ClinVar variants: 99
• Clinical trials: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy
Mondo ID	MONDO:0005336
EFO	EFO:0004145
DOID	DOID:423
ICD-11	1870184184
NCIT	C101216
SNOMED CT	129565002
UMLS	C0026848
MedGen	10135
Is cancer (heuristic)	no

Data availability: 99 ClinVar variants · 47 GWAS associations (15 studies) · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 32 Mondo subtypes.

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

Related subtypes (12): anismus, skeletal muscle neoplasm, Volkmann contracture, diaphragm disorder, anterior compartment of tibia syndrome, rotator cuff syndrome, Cyprus facial-neuromusculoskeletal syndrome, Tel Hashomer camptodactyly syndrome, muscular dystrophy-white matter spongiosis syndrome, acquired skeletal muscle disease, myotonic syndrome, hereditary skeletal muscle disorder

Subtypes (32): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, myopathy due to myoadenylate deaminase deficiency, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, metabolic myopathy, myositis disease, collagen 6-related myopathy, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in POMT2, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Genetics & variants

GWAS landscape

47 GWAS associations across 15 studies. Top hits map to 28 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4149056	3e-09	SLCO1B1	?	5.15
rs73089338	2e-07	CDCP1	?	4.63
rs61865606	3e-07	LINC03068	?	2.56
rs77051277	4e-07	LINC02988	?	50.9
rs142915950	4e-07	KCNIP4	?
rs28447350	5e-07	LINC00355 - LGMNP1	?	3.66
rs6925743	9e-07	PPP1R14C	?	5.26
rs13260471	9e-07	PPP1R3B-DT	?
rs140854723	1e-06	EVC2	?	66.1
rs10872257	1e-06	ATP5MGP2 - CLVS2	?	2.17
rs11780883	1e-06	LINC01419 - TPM3P3	?	4.55
rs10871700	1e-06	LINC01899 - CBLN2	?	3.33
rs33428	1e-06	ZNF536	?	3.85
rs333114	2e-06	SPNS2-AS1	?	3.22
rs7779564	2e-06	ABCA13 - LINC02838	?	3.37
rs2247256	2e-06	ERICH1	?	6.25
rs11519272	3e-06	SLCO1B1	?	2.37
rs504365	3e-06	RASGRF2	?	1.25
rs4149000	3e-06	SLCO1A2	?	3.94
rs9831928	3e-06	SGO1-AS1 - VENTXP7	?	4.76
rs4256319	3e-06	ADCY2	?	50
rs34312380	3e-06	ZNF676	?	4.76
rs72648866	4e-06	TBX21	?	3.37
rs145427387	4e-06	RNU6-54P - MTCL1P1	?	2.33
rs28420503	4e-06	ZNF92P2 - PCGF7P	?	4.79
rs2861137	5e-06	KIAA1328	?
rs10795948	5e-06	CDC123 - RN7SL198P	?	2.13
rs187058151	5e-06	CCDC91 - FAR2	?	1.94
rs62131018	5e-06	ALK	?	1.99
rs55902659	5e-06	SLC12A2 - FBN2	?	2.27

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90652218	Liu TY	2025	1,888	227,658	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90652097	Liu TY	2025	1,848	227,658	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477611	Verma A	2024	1,688	447,194	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477613	Verma A	2024	1,451	447,597	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477610	Verma A	2024	676	120,358	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481062	Verma A	2024	676	120,358	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477612	Verma A	2024	642	120,432	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481042	Verma A	2024	642	120,432	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435956	Zhou W	2018	470	406,852	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90473358	UK Biobank Whole-Genome Sequencing Consortium	2025	457	457,983	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	9

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	12
missense_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4149056	12	21178615	T>A,C	0.05	missense_variant	SLCO1B1	3e-09	Tier 1: coding
rs73089338	3	45114350	T>C,G	0.05	intron_variant	CDCP1	2e-07	Tier 4: intronic/intergenic
rs61865606	10	132440647	T>C,G	0.05	intron_variant	LINC03068	3e-07	Tier 4: intronic/intergenic
rs77051277	1	150167075	A>G	0.05	intron_variant	LINC02988	4e-07	Tier 4: intronic/intergenic
rs142915950	4	21079510	A>G		intron_variant	KCNIP4	4e-07	Tier 4: intronic/intergenic
rs28447350	13	64923076	G>A,C	0.05	intergenic_variant	LINC00355 - LGMNP1	5e-07	Tier 4: intronic/intergenic
rs6925743	6	150170920	T>A	0.05	intron_variant	PPP1R14C	9e-07	Tier 4: intronic/intergenic
rs13260471	8	9175136	A>G	0.05	intron_variant	PPP1R3B-DT	9e-07	Tier 4: intronic/intergenic
rs140854723	4	5634585	G>A,T		intron_variant	EVC2	1e-06	Tier 4: intronic/intergenic
rs10872257	6	122969896	C>A,T	0.05	intergenic_variant	ATP5MGP2 - CLVS2	1e-06	Tier 4: intronic/intergenic
rs11780883	8	83834281	G>A,T	0.05	intergenic_variant	LINC01419 - TPM3P3	1e-06	Tier 4: intronic/intergenic
rs10871700	18	72302261	A>C,G,T	0.05	intergenic_variant	LINC01899 - CBLN2	1e-06	Tier 4: intronic/intergenic
rs33428	19	30446936	A>G	0.05	intron_variant	ZNF536	1e-06	Tier 4: intronic/intergenic
rs333114	17	4495991	A>C,G,T	0.05	intron_variant	SPNS2-AS1	2e-06	Tier 4: intronic/intergenic
rs7779564	7	48686597	A>C,G,T	0.05	intergenic_variant	ABCA13 - LINC02838	2e-06	Tier 4: intronic/intergenic
rs2247256	8	666484	G>A,T	0.05	intron_variant	ERICH1	2e-06	Tier 4: intronic/intergenic
rs11519272	12	21209458	C>A,G,T	0.05	intron_variant	SLCO1B1	3e-06	Tier 4: intronic/intergenic
rs504365	5	81012056	G>A,C,T	0.05	intron_variant	RASGRF2	3e-06	Tier 4: intronic/intergenic
rs4149000	12	21295063	C>T	0.05	intron_variant	SLCO1A2	3e-06	Tier 4: intronic/intergenic
rs9831928	3	21224048	T>C,G	0.05	intron_variant	SGO1-AS1 - VENTXP7	3e-06	Tier 4: intronic/intergenic
rs4256319	5	7538189	T>A,C	0.05	intron_variant	ADCY2	3e-06	Tier 4: intronic/intergenic
rs34312380	19	22207269	C>T	0.05	intergenic_variant	ZNF676	3e-06	Tier 4: intronic/intergenic
rs72648866	17	47735928	T>A	0.05	intron_variant	TBX21	4e-06	Tier 4: intronic/intergenic
rs145427387	13	70725683	AATT>A	0.05	intergenic_variant	RNU6-54P - MTCL1P1	4e-06	Tier 4: intronic/intergenic
rs28420503	19	22133911	A>G	0.05	intergenic_variant	ZNF92P2 - PCGF7P	4e-06	Tier 4: intronic/intergenic
rs2861137	18	37141725	G>A,T	0.05	intron_variant	KIAA1328	5e-06	Tier 4: intronic/intergenic
rs10795948	10	12308135	C>A,G,T	0.05	intergenic_variant	CDC123 - RN7SL198P	5e-06	Tier 4: intronic/intergenic
rs187058151	12	28675079	A>C	0.05	intron_variant	CCDC91 - FAR2	5e-06	Tier 4: intronic/intergenic
rs62131018	2	29828498	C>A,G,T	0.05	intron_variant	ALK	5e-06	Tier 4: intronic/intergenic
rs55902659	5	128209813	C>G	0.05	intergenic_variant	SLC12A2 - FBN2	5e-06	Tier 4: intronic/intergenic

ClinVar germline variants

99 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 21 pathogenic, 21 conflicting classifications of pathogenicity, 17 likely pathogenic, 8 pathogenic/likely pathogenic, 4 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
203585	NM_000018.4(ACADVL):c.1376G>A (p.Arg459Gln)	ACADVL	Pathogenic	reviewed by expert panel
2582817	NM_001100.4(ACTA1):c.889G>A (p.Ala297Thr)	ACTA1	Pathogenic	criteria provided, single submitter
2164	NM_213599.3(ANO5):c.191dup (p.Asn64fs)	ANO5	Pathogenic	reviewed by expert panel
7350	NM_012210.4(TRIM32):c.1459G>A (p.Asp487Asn)	ASTN2	Pathogenic	criteria provided, multiple submitters, no conflicts
17621	NM_000070.3(CAPN3):c.550del (p.Thr184fs)	CAPN3	Pathogenic	reviewed by expert panel
17545	NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter)	CLCN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210745	NM_001848.3(COL6A1):c.1003-2A>G	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
210752	NM_004369.4(COL6A3):c.6181C>T (p.Arg2061Ter)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374059	NM_004006.3(DMD):c.5699T>G (p.Leu1900Ter)	DMD	Pathogenic	criteria provided, single submitter
689572	NM_004006.3(DMD):c.7580T>A (p.Leu2527Ter)	DMD	Pathogenic	no assertion criteria provided
7282	NM_001005361.3(DNM2):c.1102G>A (p.Glu368Lys)	DNM2	Pathogenic	reviewed by expert panel
523333	NM_000117.3(EMD):c.184dup (p.Ser62fs)	EMD	Pathogenic	criteria provided, single submitter
4221	NM_024301.5(FKRP):c.826C>A (p.Leu276Ile)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4027	NM_000152.5(GAA):c.-32-13T>G	GAA	Pathogenic	reviewed by expert panel
5919	NM_000334.4(SCN4A):c.2024G>A (p.Arg675Gln)	GH-LCR	Pathogenic	criteria provided, multiple submitters, no conflicts
164324	NM_000257.4(MYH7):c.2572C>T (p.Arg858Cys)	LOC126861898	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812933	NC_000023.11:g.150583230_150648535del	MTM1	Pathogenic	no assertion criteria provided
1320041	NM_201384.3(PLEC):c.6970C>T (p.Arg2324Ter)	PLEC	Pathogenic	criteria provided, multiple submitters, no conflicts
8046	NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8054	NM_005055.5(RAPSN):c.490C>T (p.Arg164Cys)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212098	NM_000540.3(RYR1):c.1878_1882del (p.Pro626_Gly627insTer)	RYR1	Pathogenic	criteria provided, multiple submitters, no conflicts
212103	NM_000540.3(RYR1):c.3381+1G>A	RYR1	Pathogenic	criteria provided, multiple submitters, no conflicts
212107	NM_000540.3(RYR1):c.8724C>A (p.Tyr2908Ter)	RYR1	Pathogenic	criteria provided, single submitter
202529	NM_001267550.2(TTN):c.107635C>T (p.Gln35879Ter)	TTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212463	NM_001267550.2(TTN):c.23903_23904delinsA (p.Gly7968fs)	TTN	Pathogenic	criteria provided, single submitter
212468	NM_001267550.2(TTN):c.42486_42489del (p.Cys14163fs)	TTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374037	NM_001267550.2(TTN):c.74567G>A (p.Trp24856Ter)	TTN	Pathogenic	criteria provided, single submitter
523259	GRCh37/hg19 17p12(chr17:14215739-15422582)	TVP23C	Pathogenic	criteria provided, single submitter
834072	NM_001267052.2(UNC45B):c.2255G>A (p.Arg752Gln)	UNC45B	Pathogenic	criteria provided, multiple submitters, no conflicts
374123	NM_000018.4(ACADVL):c.1358G>A (p.Arg453Gln)	ACADVL	Likely pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 170 · 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
MYBPC1	Strong	Autosomal dominant	myopathy, congenital, with tremor	11
PACSIN3	Moderate	Autosomal recessive	myopathy	2
COL6A6	Limited	Autosomal recessive	myopathy	2
P2RX6	Limited	Autosomal recessive	myopathy

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYBPC1	Orphanet:1146	Distal arthrogryposis type 1
MYBPC1	Orphanet:137783	Lethal congenital contracture syndrome type 3
MYBPC1	Orphanet:498693	MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita 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
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
SLCO1B1	Orphanet:3111	Rotor syndrome
SLC2A1	Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin
SLC2A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SLC2A1	Orphanet:2131	Alternating hemiplegia of childhood
SLC2A1	Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1	Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome
SLC2A1	Orphanet:86911	Epilepsy with myoclonic absences
SLC2A1	Orphanet:98811	Paroxysmal exertion-induced dyskinesia
TK2	Orphanet:254875	Mitochondrial DNA depletion syndrome, myopathic form
TK2	Orphanet:254886	Autosomal recessive progressive external ophthalmoplegia
TNNT1	Orphanet:98902	Amish nemaline myopathy
TPM3	Orphanet:171433	Intermediate nemaline myopathy
TPM3	Orphanet:171439	Childhood-onset nemaline myopathy
TPM3	Orphanet:171881	Cap myopathy
TPM3	Orphanet:178342	Inflammatory myofibroblastic tumor
TPM3	Orphanet:2020	Congenital fiber-type disproportion myopathy
TPM3	Orphanet:476406	Congenital generalized hypercontractile muscle stiffness 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

Cohort genes → proteins

75 cohort genes, 72 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	25
multi_evidence	50

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL6A6	HGNC:27023	ENSG00000206384	A6NMZ7	Collagen alpha-6(VI) chain	gencc
MYBPC1	HGNC:7549	ENSG00000196091	Q00872	Myosin-binding protein C, slow-type	gencc
P2RX6	HGNC:8538	ENSG00000099957	O15547	P2X purinoceptor 6	gencc
PACSIN3	HGNC:8572	ENSG00000165912	Q9UKS6	Protein kinase C and casein kinase substrate in neurons protein 3	gencc
RNGTT	HGNC:10073	ENSG00000111880	O60942	mRNA-capping enzyme	gwas
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
SCN4A	HGNC:10591	ENSG00000007314	P35499	Sodium channel protein type 4 subunit alpha	clinvar
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gwas
SLCO1A2	HGNC:10956	ENSG00000084453	P46721	Solute carrier organic anion transporter family member 1A2	gwas
SLCO1B1	HGNC:10959	ENSG00000134538	Q9Y6L6	Solute carrier organic anion transporter family member 1B1	gwas
SLC2A1	HGNC:11005	ENSG00000117394	P11166	Solute carrier family 2, facilitated glucose transporter member 1	clinvar
TBX21	HGNC:11599	ENSG00000073861	Q9UL17	T-box transcription factor TBX21	gwas
TK2	HGNC:11831	ENSG00000166548	O00142	Thymidine kinase 2, mitochondrial	clinvar
TNNT1	HGNC:11948	ENSG00000105048	P13805	Troponin T, slow skeletal muscle	clinvar
TPM3	HGNC:12012	ENSG00000143549	P06753	Tropomyosin alpha-3 chain	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	clinvar
ZNF257	HGNC:13498	ENSG00000197134	Q9Y2Q1	Zinc finger protein 257	gwas
ARHGEF10	HGNC:14103	ENSG00000104728	O15013	Rho guanine nucleotide exchange factor 10	clinvar
UNC45B	HGNC:14304	ENSG00000141161	Q8IWX7	Protein unc-45 homolog B	clinvar
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar
PPP1R14C	HGNC:14952	ENSG00000198729	Q8TAE6	Protein phosphatase 1 regulatory subunit 14C	gwas
CASQ1	HGNC:1512	ENSG00000143318	P31415	Calsequestrin-1	clinvar
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	clinvar
ASTN2	HGNC:17021	ENSG00000148219	O75129	Astrotactin-2	clinvar
BICD2	HGNC:17208	ENSG00000185963	Q8TD16	Protein bicaudal D homolog 2	clinvar
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	clinvar
EVC2	HGNC:19747	ENSG00000173040	Q86UK5	Limbin	gwas
ATG14	HGNC:19962	ENSG00000126775	Q6ZNE5	Beclin 1-associated autophagy-related key regulator	gwas
CLCN1	HGNC:2019	ENSG00000188037	P35523	Chloride channel protein 1	clinvar
ZNF676	HGNC:20429	ENSG00000196109	Q8N7Q3	Zinc finger protein 676	gwas
ADTRP	HGNC:21214	ENSG00000111863	Q96IZ2	Androgen-dependent TFPI-regulating protein	gwas
COL6A1	HGNC:2211	ENSG00000142156	P12109	Collagen alpha-1(VI) chain	clinvar
COL6A2	HGNC:2212	ENSG00000142173	P12110	Collagen alpha-2(VI) chain	clinvar
COL6A3	HGNC:2213	ENSG00000163359	P12111	Collagen alpha-3(VI) chain	clinvar
ADCY2	HGNC:233	ENSG00000078295	Q08462	Adenylate cyclase type 2	gwas
CPT2	HGNC:2330	ENSG00000157184	P23786	Carnitine O-palmitoyltransferase 2, mitochondrial	clinvar
CDCP1	HGNC:24357	ENSG00000163814	Q9H5V8	CUB domain-containing protein 1	gwas
SARNP	HGNC:24432	ENSG00000205323	P82979	SAP domain-containing ribonucleoprotein	clinvar
CSPG4	HGNC:2466	ENSG00000173546	Q6UVK1	Chondroitin sulfate proteoglycan 4	gwas
TRAPPC11	HGNC:25751	ENSG00000168538	Q7Z392	Trafficking protein particle complex subunit 11	clinvar
PIEZO2	HGNC:26270	ENSG00000154864	Q9H5I5	Piezo-type mechanosensitive ion channel component 2	clinvar
DAG1	HGNC:2666	ENSG00000173402	Q14118	Dystroglycan 1	clinvar
ERICH1	HGNC:27234	ENSG00000104714	Q86X53	Glutamate-rich protein 1	gwas
ANO5	HGNC:27337	ENSG00000171714	Q75V66	Anoctamin-5	clinvar
XKR6	HGNC:27806	ENSG00000171044	Q5GH73	XK-related protein 6	gwas
C16orf78	HGNC:28479	ENSG00000166152	Q8WTQ4	Uncharacterized protein C16orf78	gwas
ZNF561	HGNC:28684	ENSG00000171469	Q8N587	Zinc finger protein 561	gwas
GARRE1	HGNC:29016	ENSG00000166398	O15063	Granule associated Rac and RHOG effector protein 1	gwas
ZNF536	HGNC:29025	ENSG00000198597	O15090	Zinc finger protein 536	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL6A6	Collagen alpha-6(VI) chain	Collagen VI acts as a cell-binding protein.
MYBPC1	Myosin-binding protein C, slow-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.
P2RX6	P2X purinoceptor 6	May act as a modulatory subunit rather than a functional channel.
PACSIN3	Protein kinase C and casein kinase substrate in neurons protein 3	Plays a role in endocytosis and regulates internalization of plasma membrane proteins.
RNGTT	mRNA-capping enzyme	Bifunctional mRNA-capping enzyme exhibiting RNA 5’-triphosphate monophosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part.
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.
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
SLCO1A2	Solute carrier organic anion transporter family member 1A2	Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate)…
SLCO1B1	Solute carrier organic anion transporter family member 1B1	Mediates the Na(+)-independent uptake of organic anions.
SLC2A1	Solute carrier family 2, facilitated glucose transporter member 1	Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.
TBX21	T-box transcription factor TBX21	Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs.
TK2	Thymidine kinase 2, mitochondrial	Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix.
TNNT1	Troponin T, slow skeletal muscle	Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TPM3	Tropomyosin alpha-3 chain	Binds to actin filaments in muscle and non-muscle cells.
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.
ZNF257	Zinc finger protein 257	May be involved in transcriptional regulation.
ARHGEF10	Rho guanine nucleotide exchange factor 10	May play a role in developmental myelination of peripheral nerves.
UNC45B	Protein unc-45 homolog B	Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain.
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.
PPP1R14C	Protein phosphatase 1 regulatory subunit 14C	Inhibitor of the PP1 regulatory subunit PPP1CA.
CASQ1	Calsequestrin-1	Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
ASTN2	Astrotactin-2	Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.
BICD2	Protein bicaudal D homolog 2	Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin.
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…
EVC2	Limbin	Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
ATG14	Beclin 1-associated autophagy-related key regulator	Required for both basal and inducible autophagy.
CLCN1	Chloride channel protein 1	Voltage-gated chloride channel involved in skeletal muscle excitability.
ZNF676	Zinc finger protein 676	May be involved in transcriptional regulation.
ADTRP	Androgen-dependent TFPI-regulating protein	Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids.
COL6A1	Collagen alpha-1(VI) chain	Collagen VI acts as a cell-binding protein.
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.
ADCY2	Adenylate cyclase type 2	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
CPT2	Carnitine O-palmitoyltransferase 2, mitochondrial	Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites.
CDCP1	CUB domain-containing protein 1	May be involved in cell adhesion and cell matrix association.
SARNP	SAP domain-containing ribonucleoprotein	Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form.
CSPG4	Chondroitin sulfate proteoglycan 4	Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis.
TRAPPC11	Trafficking protein particle complex subunit 11	Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
PIEZO2	Piezo-type mechanosensitive ion channel component 2	Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.
DAG1	Dystroglycan 1	The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my…
ANO5	Anoctamin-5	Plays a role in plasma membrane repair in a process involving annexins.
ZNF561	Zinc finger protein 561	May be involved in transcriptional regulation.
GARRE1	Granule associated Rac and RHOG effector protein 1	Acts as an effector of RAC1.
ZNF536	Zinc finger protein 536	Transcriptional repressor that negatively regulates neuron differentiation by repressing retinoic acid-induced gene transcription.
DLGAP1	Disks large-associated protein 1	Part of the postsynaptic scaffold in neuronal cells.
SMCHD1	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture.
KIAA1328	Protein hinderin	Competes with SMC1 for binding to SMC3.

Protein-family classification

Druggable: 22 · Difficult: 10 · Unknown: 43 · Druggable fraction: 0.29

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
Complement	1	3.6×	0.674
Transporter	3	3.1×	0.674
Ion channel	2	3.0×	0.674
Phosphatase	2	2.2×	0.674
Antibody/Immunoglobulin	3	1.2×	0.703
Enzyme (other)	7	1.1×	0.703
Kinase	3	1.1×	0.703
Other/Unknown	43	1.0×	0.703
Transcription factor	7	0.8×	0.875
Scaffold/PPI	3	0.7×	0.875
Protease	1	0.5×	0.875

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL6A6	Other/Unknown	no		VWF_A, Collagen, vWFA_dom_sf
MYBPC1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
P2RX6	Other/Unknown	no		P2X_purnocptor, P2X6_purnocptor, P2X_extracellular_dom_sf
PACSIN3	Scaffold/PPI	no		FCH_dom, SH3_domain, AH/BAR_dom_sf
RNGTT	Phosphatase	yes	2.7.7.50	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, mRNA_cap_enzyme_adenylation
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
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
SLCO1A2	Transporter	yes		Kazal_dom, OATP, MFS_dom
SLCO1B1	Transporter	yes		Kazal_dom, OATP, MFS_dom
SLC2A1	Transporter	yes		Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like
TBX21	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TK2	Kinase	yes	2.7.1.21	DCK/DGK, P-loop_NTPase, DNK_dom
TNNT1	Other/Unknown	no		Troponin, TNNT, Troponin_sf
TPM3	Other/Unknown	no		Tropomyosin
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
ZNF257	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ARHGEF10	Scaffold/PPI	no		DH_dom, WD40/YVTN_repeat-like_dom_sf, DBL_dom_sf
UNC45B	Other/Unknown	no		Armadillo, ARM-like, TPR-like_helical_dom_sf
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
PPP1R14C	Other/Unknown	no		CPI-17, CPI-17_sf
CASQ1	Other/Unknown	no		Calsequestrin, Calsequestrin_CS, Thioredoxin-like_sf
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
ASTN2	Complement	yes		MACPF, Astrotactin, FN3_sf
BICD2	Other/Unknown	no		BICD
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N
EVC2	Other/Unknown	no		Limbin, Limbin/EVC
ATG14	Enzyme (other)	yes	2.7.1.137	UV_resistance/autophagy_Atg14
CLCN1	Other/Unknown	no		ClC, Cl_channel-1, Cl-channel_core
ZNF676	Transcription factor	no		KRAB, Znf_C2H2_type, Znf_C2H2_sf
ADTRP	Other/Unknown	no		ADTRP_AIG1
COL6A1	Other/Unknown	no		VWF_A, Collagen, vWFA_dom_sf
COL6A2	Other/Unknown	no		VWF_A, Collagen, vWFA_dom_sf
COL6A3	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom
ADCY2	Enzyme (other)	yes	4.6.1.1	A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
CPT2	Enzyme (other)	yes	2.3.1.21	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2
CDCP1	Other/Unknown	no		Sperma_CUB_dom_sf, CDCP1, CDCP1_CUB_3rd_6th
SARNP	Other/Unknown	no		SAP_dom, SAP_dom_sf, SAP_domain_ribonucleoprotein
CSPG4	Other/Unknown	no		Laminin_G, ConA-like_dom_sf, CSPG_rpt
TRAPPC11	Other/Unknown	no		TPC11, TRAPPC11_C
PIEZO2	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28
DAG1	Antibody/Immunoglobulin	yes		Cadg, DAG1_C, Ig-like_fold
ERICH1	Other/Unknown	no		ERICH1
ANO5	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
XKR6	Other/Unknown	no		XK-rel, XK-related_scramblase
C16orf78	Other/Unknown	no		DUF4638
ZNF561	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
GARRE1	Other/Unknown	no		DUF4745, GARRE1
ZNF536	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Krueppel_C2H2-ZF

Expression context

Cohort genes with no expression data: 1.

66 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)	74
unknown	1

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	12
skeletal muscle tissue of rectus abdominis	8
sural nerve	7
calcaneal tendon	7
buccal mucosa cell	6
gluteal muscle	6
cardiac muscle of right atrium	5
skeletal muscle tissue of biceps brachii	5
male germ line stem cell (sensu Vertebrata) in testis	5
primordial germ cell in gonad	5
gastrocnemius	4
apex of heart	4
left ventricle myocardium	4
dorsal root ganglion	4
mucosa of transverse colon	4
sperm	4
colonic epithelium	4
corpus callosum	3
blood	3
granulocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL6A6	140		marker	buccal mucosa cell, parietal pleura, cardiac muscle of right atrium
MYBPC1	225	broad	marker	biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
P2RX6	159		yes	gastrocnemius, muscle of leg, hindlimb stylopod muscle
PACSIN3	216	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
RNGTT	262	ubiquitous	marker	cardia of stomach, nipple, pylorus
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
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion
SLCO1A2	155	tissue_specific	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
SLCO1B1	29	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SLC2A1	250	ubiquitous	marker	tibial nerve, sural nerve, skin of abdomen
TBX21	149	broad	marker	granulocyte, blood, male germ line stem cell (sensu Vertebrata) in testis
TK2	280	ubiquitous	marker	calcaneal tendon, sural nerve, adrenal tissue
TNNT1	192	ubiquitous	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm
TPM3	243	ubiquitous	marker	diaphragm, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
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
ZNF257	167	broad	marker	primordial germ cell in gonad, oocyte, male germ line stem cell (sensu Vertebrata) in testis
ARHGEF10	134	ubiquitous	yes	sural nerve, tibial nerve, right lung
UNC45B	111	tissue_specific	yes	left ventricle myocardium, cardiac muscle of right atrium, tibialis anterior
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord
PPP1R14C	229	broad	marker	upper arm skin, cardiac muscle of right atrium, left ventricle myocardium
CASQ1	195	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gluteal muscle
ACTN2	226	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle
ASTN2	236	ubiquitous	marker	buccal mucosa cell, trigeminal ganglion, dorsal root ganglion
BICD2	290	ubiquitous	marker	gingival epithelium, gingiva, hair follicle
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle
EVC2	182	ubiquitous	marker	pancreatic ductal cell, calcaneal tendon, primordial germ cell in gonad
ATG14	292	ubiquitous	marker	secondary oocyte, oocyte, gluteal muscle
CLCN1	108	tissue_specific	marker	hindlimb stylopod muscle, triceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 42.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A1	5,711
ALK	4,792
DNM2	4,715
KPNB1	4,456
TTN	4,237
DYNC1H1	4,215
TPM3	4,099
FBN1	3,640
EMD	3,503
COL6A1	3,049

Intra-cohort edges

A	B	Sources
ACTN2	DYSF	intact
ACTN2	TTN	string_interaction
ADTRP	EVC2	string_interaction
ALK	BICD2	biogrid_interaction
ALK	TPM3	string_interaction
ANO5	DYSF	string_interaction
ANO5	FKRP	string_interaction
BICD2	DYNC1H1	string_interaction
CAPN3	DMD	string_interaction
CAPN3	DYSF	string_interaction
CAPN3	FKRP	string_interaction
CAPN3	MYBPC1	biogrid_interaction, intact
CAPN3	TTN	biogrid_interaction, intact, string_interaction
CASQ1	RYR1	string_interaction
CLCN1	RYR1	string_interaction
CLCN1	SCN4A	string_interaction
COL6A1	COL6A2	string_interaction
COL6A1	COL6A3	string_interaction
COL6A2	COL6A3	string_interaction
COL6A2	COL6A6	string_interaction
COL6A2	DMD	string_interaction
COL6A3	DYSF	intact
COL6A3	FBN1	string_interaction
DAG1	DMD	intact, string_interaction
DAG1	DPM3	string_interaction
DAG1	FKRP	string_interaction
DMD	DYSF	string_interaction
DNM2	KPNB1	intact
DNM2	MTM1	string_interaction
DNM2	PACSIN3	string_interaction
DPM3	FKRP	string_interaction
DPM3	GARRE1	string_interaction
DYSF	FKRP	string_interaction
DYSF	MTM1	string_interaction
DYSF	MYBPC1	biogrid_interaction, intact
DYSF	TTN	biogrid_interaction, intact
EMD	EVC2	biogrid_interaction
KPNB1	RNGTT	intact
MTM1	RYR1	string_interaction
MYBPC1	TNNT1	string_interaction
RYR1	TTN	intact
TNNT1	TPM3	biogrid_interaction, intact, string_interaction

Structural data

PDB: 41 · AlphaFold-only: 31 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNC1H1	Q14204	97
ALK	Q9UM73	79
TTN	Q8WZ42	64
KPNB1	Q14974	23
GAA	P10253	19
ISCU	Q9H1K1	18
ACTN2	P35609	16
SLC12A2	P55011	14
ERCC1	P07992	14
DYSF	O75923	11
FBN1	P35555	11
RNGTT	O60942	9
SLCO1B1	Q9Y6L6	9
CLCN1	P35523	9
GGPS1	O95749	9
MYBPC1	Q00872	8
FKRP	Q9H9S5	8
DAG1	Q14118	8
ATG14	Q6ZNE5	7
CASQ1	P31415	6
COL6A3	P12111	6
DMD	P11532	6
EMD	P50402	6
SLC2A1	P11166	5
ACTA1	P68133	5
CAPN3	P20807	5
LCOR	Q96JN0	4
SCN4A	P35499	3
ASTN2	O75129	3
CSPG4	Q6UVK1	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPT2	P23786	94.52
ETFDH	Q16134	93.60
ADTRP	Q96IZ2	90.99
MTM1	Q13496	90.10
DPM3	Q9P2X0	88.73
UNC45B	Q8IWX7	88.38
TRAPPC11	Q7Z392	87.76
PACSIN3	Q9UKS6	87.12
TK2	O00142	85.01
P2RX6	O15547	83.89
MSTO1	Q9BUK6	83.83
ANO5	Q75V66	82.22
SLCO1A2	P46721	79.97
ADCY2	Q08462	78.91
CDCP1	Q9H5V8	78.13
COL6A6	A6NMZ7	75.61
TNNT1	P13805	74.89
EVC2	Q86UK5	73.33
ZNF676	Q8N7Q3	72.69
PNPLA2	Q96AD5	72.56
ZNF257	Q9Y2Q1	67.58
ERICH1	Q86X53	65.82
ARHGEF10	O15013	65.56
XKR6	Q5GH73	64.85
PPP1R14C	Q8TAE6	64.37
TBX21	Q9UL17	61.95
KIAA1328	Q86T90	61.43
ZNF561	Q8N587	60.21
TVP23C	Q96ET8	59.62
C16orf78	Q8WTQ4	55.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 339. Enrichment computed across 83 evidence-associated genes (63 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 63 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	7	34.3×	3e-07	TNNT1, TPM3, TTN, ACTA1, ACTN2, DMD, MYBPC1
Assembly of collagen fibrils and other multimeric structures	5	15.9×	0.002	COL6A1, COL6A2, COL6A3, COL6A6, PLEC
Collagen biosynthesis and modifying enzymes	5	13.5×	0.004	COL6A1, COL6A2, COL6A3, COL6A6, PLOD1
Collagen chain trimerization	4	16.5×	0.005	COL6A1, COL6A2, COL6A3, COL6A6
Signaling by PDGF	4	16.1×	0.005	COL6A1, COL6A2, COL6A3, COL6A6
NCAM1 interactions	4	15.8×	0.005	COL6A1, COL6A2, COL6A3, COL6A6
ECM proteoglycans	5	11.9×	0.005	COL6A1, COL6A2, COL6A3, DAG1, COL6A6
Integrin cell surface interactions	5	10.7×	0.005	COL6A1, COL6A2, COL6A3, COL6A6, FBN1
Muscle contraction	6	7.3×	0.006	RYR1, SCN4A, ACTA1, CASQ1, ACTN2, MYBPC1
Collagen degradation	4	11.2×	0.015	COL6A1, COL6A2, COL6A3, COL6A6
Formation of the dystrophin-glycoprotein complex (DGC)	3	14.7×	0.033	ACTA1, DAG1, DMD
Stimuli-sensing channels	4	8.6×	0.033	RYR1, CASQ1, CLCN1, ANO5
Organic anion transport by SLCO transporters	2	33.0×	0.042	SLCO1A2, SLCO1B1
Matriglycan biosynthesis on DAG1	2	25.9×	0.063	FKRP, DAG1
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)	1	181.3×	0.064	SLC2A1
Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR)	1	181.3×	0.064	SLCO1B1
Maturation of replicase proteins	1	181.3×	0.064	ISCU
Drug resistance of ALK mutants	1	181.3×	0.064	ALK
ASP-3026-resistant ALK mutants	1	181.3×	0.064	ALK
NVP-TAE684-resistant ALK mutants	1	181.3×	0.064	ALK
alectinib-resistant ALK mutants	1	181.3×	0.064	ALK
brigatinib-resistant ALK mutants	1	181.3×	0.064	ALK
ceritinib-resistant ALK mutants	1	181.3×	0.064	ALK
crizotinib-resistant ALK mutants	1	181.3×	0.064	ALK
lorlatinib-resistant ALK mutants	1	181.3×	0.064	ALK
Glycogen breakdown (glycogenolysis)	2	24.2×	0.064	GAA, PYGM
Recycling of bile acids and salts	2	19.1×	0.064	SLCO1A2, SLCO1B1
Initiation of Nuclear Envelope (NE) Reformation	2	19.1×	0.064	EMD, KPNB1
Ras activation upon Ca2+ influx through NMDA receptor	2	18.1×	0.064	ACTN2, RASGRF2
Bile acid and bile salt metabolism	2	15.8×	0.079	SLCO1A2, SLCO1B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 74 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	10	28.1×	1e-09	RYR1, SCN4A, TPM3, TTN, ACTA1, FKRP, CLCN1, EMD (+2 more)
sarcomere organization	7	36.2×	2e-07	TNNT1, TTN, CAPN3, CASQ1, ACTN2, MYBPC1, PLEC
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	17.1×	3e-04	FKRP, ATG14, COL6A1, COL6A2, COL6A3, MTM1
muscle cell cellular homeostasis	4	35.0×	7e-04	CAPN3, DMD, GAA, MTM1
skeletal muscle fiber development	4	29.4×	0.001	RYR1, ACTA1, COL6A1, PLEC
myelination in peripheral nervous system	3	36.0×	0.006	ARHGEF10, COL6A1, DAG1
skeletal muscle tissue regeneration	3	36.0×	0.006	FKRP, COL6A1, DAG1
muscle organ development	5	11.3×	0.006	UNC45B, CAPN3, COL6A3, DMD, EMD
regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	2	113.9×	0.008	CASQ1, DMD
skeletal muscle thin filament assembly	2	75.9×	0.013	TTN, ACTA1
skeletal muscle tissue growth	2	75.9×	0.013	COL6A1, MTM1
cardiac muscle cell development	3	25.3×	0.013	TTN, ACTN2, PLEC
response to muscle activity	3	23.6×	0.013	CAPN3, COL6A1, DAG1
response to denervation involved in regulation of muscle adaptation	2	65.1×	0.016	CASQ1, DAG1
basement membrane organization	3	20.7×	0.016	FKRP, COL6A1, DAG1
cellular response to mechanical stimulus	4	11.7×	0.016	SLC2A1, PIEZO2, DAG1, PLEC
mitochondrion distribution	2	56.9×	0.019	MSTO1, MTM1
skeletal muscle fiber differentiation	2	45.5×	0.027	FKRP, COL6A1
cardiac muscle contraction	3	16.3×	0.027	TTN, DMD, GAA
heart morphogenesis	3	15.2×	0.031	FKRP, DAG1, GAA
response to UV	3	14.8×	0.032	COL6A1, COL6A2, COL6A3
fatty acid beta-oxidation using acyl-CoA dehydrogenase	2	38.0×	0.034	ETFDH, ACADVL
tissue remodeling	2	35.0×	0.036	COL6A1, CSPG4
negative regulation of protein localization to cell surface	2	35.0×	0.036	ACTN2, ASTN2
mitochondrion organization	4	8.2×	0.036	COL6A1, MSTO1, MTM1, PLEC
glycogen catabolic process	2	32.5×	0.040	GAA, PYGM
maltose metabolic process	1	227.7×	0.042	GAA
monocyte activation involved in immune response	1	227.7×	0.042	DYSF
sucrose metabolic process	1	227.7×	0.042	GAA
muscle attachment	1	227.7×	0.042	DAG1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine.

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 10 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 37 of 83 evidence-associated genes (45%) 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
SLC12A2	BUMETANIDE
SLCO1A2	RIFAMPIN
SLCO1B1	CANDESARTAN CILEXETIL
SLC2A1	EMETINE
TK2	SORIVUDINE
CPT2	PERHEXILINE
GAA	DIENESTROL
GGPS1	MINODRONIC ACID
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GAA	112	4
ALK	61	4
SLCO1B1	57	4
SCN4A	24	4
SLC2A1	7	4
GGPS1	4	4
SLCO1A2	2	4
CPT2	2	4
RNGTT	1	2
SLC12A2	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CARBAMAZEPINE	4	SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	GAA, SCN4A
LIDOCAINE	4	SCN4A
IMIPRAMINE	4	SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	SCN4A
NIFEDIPINE	4	SCN4A
DILTIAZEM	4	SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	SCN4A
BUMETANIDE	4	SLC12A2
RIFAMPIN	4	SLCO1A2, SLCO1B1
RIFAMYCIN	4	SLCO1A2, SLCO1B1
CANDESARTAN CILEXETIL	4	SLCO1B1
TELMISARTAN	4	SLCO1B1
SIMVASTATIN	4	SLCO1B1
TELITHROMYCIN	4	SLCO1B1
PRAVASTATIN	4	SLCO1B1
MOMETASONE FUROATE	4	SLCO1B1
ATAZANAVIR	4	SLCO1B1
HYDROXYZINE PAMOATE	4	SLCO1B1
ERYTHROMYCIN ETHYLSUCCINATE	4	SLCO1B1
OLMESARTAN MEDOXOMIL	4	SLCO1B1
DICLOXACILLIN SODIUM	4	SLCO1B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 14.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1
GAA	280	Binding:267, Functional:13
SLCO1B1	242	Functional:106, ADMET:82, Binding:53, Toxicity:1
SLC2A1	158	Binding:130, ADMET:24, Functional:4
GGPS1	129	Binding:128, ADMET:1
SCN4A	95	Binding:69, Functional:18, ADMET:7, Toxicity:1
SLCO1A2	70	Functional:60, ADMET:9, Binding:1
ADCY2	31	Binding:29, Functional:2
ERCC1	28	Binding:28
TPM3	18	Binding:18
TK2	17	Binding:17
RYR1	16	Binding:13, Functional:3
DNM2	15	Binding:15
SLC12A2	13	Binding:9, Functional:4
CPT2	12	Binding:12
KPNB1	10	Binding:8, Functional:2
SMCHD1	7	Binding:7
DYNC1H1	7	Binding:7
RNGTT	6	Binding:6
PNPLA2	5	Binding:5
P2RX6	4	Functional:2, Binding:2
DAG1	4	Binding:4
TTN	1	Binding:1
ATG14	1	Binding:1
SARNP	1	Binding:1
EMD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNGTT	2.7.7.50, 3.6.1.74	mRNA guanylyltransferase, mRNA 5’-phosphatase
TK2	2.7.1.21	thymidine kinase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3
ATG14	2.7.1.137	phosphatidylinositol 3-kinase
ADCY2	4.6.1.1	adenylate cyclase
CPT2	2.3.1.21	carnitine O-palmitoyltransferase
DNM2	3.6.5.5	dynamin GTPase
DPM3	2.4.1.83	dolichyl-phosphate beta-D-mannosyltransferase
ETFDH	1.5.5.1	electron-transferring-flavoprotein dehydrogenase
GAA	3.2.1.20	alpha-glucosidase
GGPS1	2.5.1.29	geranylgeranyl diphosphate synthase
ALK	2.7.10.1	receptor protein-tyrosine kinase
MTM1	3.1.3.64, 3.1.3.95	phosphatidylinositol-3-phosphatase, phosphatidylinositol-3,5-bisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SLCO1B1	242
SLC2A1	158
GAA	280
GGPS1	129
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1
SLCO1B1	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)
CARBAMAZEPINE	4	SCN4A
PHENYTOIN	4	SCN4A
LAMOTRIGINE	4	SCN4A
RILUZOLE	4	GAA, SCN4A
LIDOCAINE	4	SCN4A
IMIPRAMINE	4	SCN4A
SERTINDOLE	4	SCN4A
PIMOZIDE	4	SCN4A
NIFEDIPINE	4	SCN4A
DILTIAZEM	4	SCN4A
MIBEFRADIL	4	SCN4A
HALOPERIDOL	4	SCN4A
MEXILETINE	4	SCN4A
AMITRIPTYLINE	4	SCN4A
AMIODARONE	4	SCN4A
CHLORPROMAZINE	4	SCN4A
BUMETANIDE	4	SLC12A2
RIFAMPIN	4	SLCO1A2, SLCO1B1
RIFAMYCIN	4	SLCO1A2, SLCO1B1
CANDESARTAN CILEXETIL	4	SLCO1B1
TELMISARTAN	4	SLCO1B1
SIMVASTATIN	4	SLCO1B1
TELITHROMYCIN	4	SLCO1B1
PRAVASTATIN	4	SLCO1B1
MOMETASONE FUROATE	4	SLCO1B1
ATAZANAVIR	4	SLCO1B1
HYDROXYZINE PAMOATE	4	SLCO1B1
ERYTHROMYCIN ETHYLSUCCINATE	4	SLCO1B1
OLMESARTAN MEDOXOMIL	4	SLCO1B1
DICLOXACILLIN SODIUM	4	SLCO1B1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	SCN4A, SLC12A2, SLCO1A2, SLCO1B1, SLC2A1, TK2, CPT2, GAA, GGPS1, ALK
B	Phased (≥1) drug, not yet approved	4	RNGTT, SMCHD1, DYNC1H1, KPNB1
C	Druggable family + PDB, no drug	8	MYBPC1, RYR1, TTN, CAPN3, ASTN2, ATG14, COL6A3, DAG1
D	Druggable family + AlphaFold only, no drug	4	ADCY2, DPM3, ETFDH, MTM1
E	Difficult family or no structure, no drug	49	COL6A6, P2RX6, PACSIN3, TBX21, TNNT1, TPM3, ACTA1, ZNF257, ARHGEF10, UNC45B (+39 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLCN1	0	SCN4A
COL6A6	0	—
MYBPC1	0	—
P2RX6	4	—
PACSIN3	0	—
RYR1	16	—
TBX21	0	—
TNNT1	0	—
TPM3	18	—
TTN	1	—
ACTA1	0	—
ZNF257	0	—
ARHGEF10	0	—
UNC45B	0	—
CAPN3	0	—
PPP1R14C	0	—
CASQ1	0	—
ACTN2	0	—
ASTN2	0	—
BICD2	0	—
FKRP	0	—
EVC2	0	—
ATG14	1	—
ZNF676	0	—
ADTRP	0	—
COL6A1	0	—
COL6A2	0	—
COL6A3	0	—
ADCY2	31	—
CDCP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 46.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	40
PHASE4	2
PHASE1/PHASE2	2
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT02124070	PHASE1/PHASE2	WITHDRAWN	Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT00937001	Not specified	ACTIVE_NOT_RECRUITING	Critical Illness Myopathy as a Cause of Debilitating ICU-Acquired Weakness
NCT01353430	Not specified	RECRUITING	Characterization of Inclusion Body Myopathy Associated With Paget’s Disease of Bone and Frontotemporal Dementia (IBMPFD)
NCT03660969	Not specified	ACTIVE_NOT_RECRUITING	Reliability of Cardiac Troponins for the Diagnosis of Myocardial Infarction in the Presence of Skeletal Muscle Disease
NCT03749538	Not specified	RECRUITING	Acute Transcranial Direct Current Stimulation in Patients With Systemic Autoimmune Myopathies
NCT04678635	Not specified	RECRUITING	Chronic Transcranial Direct Current Stimulation in Patients With Systemic Autoimmune Myopathies
NCT05599568	Not specified	RECRUITING	Repeated Bout Effect i Neuromuscular Diseases
NCT06374719	Not specified	RECRUITING	WiTNNess - TNNT1 Myopathy Natural History Study
NCT06666816	Not specified	RECRUITING	Observational Study to Observe Variations of Gait Parameters in Patients With Neuromuscular Diseases
NCT07488806	Not specified	RECRUITING	Natural History Study for Patients With Nemaline Myopathy in Spain
NCT07502989	Not specified	RECRUITING	Muscle Health Measurements Using Electrical Impedance Myography
NCT00549029	Not specified	UNKNOWN	The Association of Genetic Polymorphisms With Statin-Induced Myopathy.
NCT00767130	Not specified	UNKNOWN	DNA Diagnostic System for Statin Safety and Efficacy
NCT00922428	Not specified	COMPLETED	PASCOE-Agil HOM-Injektopas in the Treatment of Rheumatic Disorders
NCT00990834	Not specified	WITHDRAWN	Muscle Characteristics Associated With Statin Therapy
NCT01022450	Not specified	UNKNOWN	Study of the Causes of the Breakdown of Muscle Fibers in Hospitalized Patients
NCT01040650	Not specified	TERMINATED	Metabolic Features of Post-Myopathy Patients Associated With Statin Treatment
NCT01047163	Not specified	COMPLETED	Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy
NCT01270269	Not specified	COMPLETED	ACT-ICU Study: Activity and Cognitive Therapy in the Intensive Care Unit
NCT01395563	Not specified	WITHDRAWN	Strength Training on Pancreatic Cancer
NCT01530841	Not specified	COMPLETED	Efficacy and Tolerance of AVAPS Mode in Myotonic Dystrophy
NCT01547767	Not specified	COMPLETED	Investigations Into ISCU Myopathy or Iron Sulfur Scaffold U Protein Myopathy
NCT01702987	Not specified	COMPLETED	Evaluation of Ubiquinol on Mitochondrial Oxidative Capacity in Statin Patients Using 31PMRS
NCT01790178	Not specified	COMPLETED	Ultrasound in Muscle Biopsy
NCT02011282	Not specified	COMPLETED	Electro-Neuro-Muscular Stimulation in ICU
NCT02104921	Not specified	COMPLETED	Innovative Ultrasound Technology in Neuromuscular Disease
NCT02118805	Not specified	COMPLETED	Innovative Measures of Speech and Swallowing Dysfunction in Neurological Disorders
NCT02235220	Not specified	UNKNOWN	Reduction of Masticatory Muscle Activity by Restoring Canine Guidance
NCT02247895	Not specified	TERMINATED	Treatment of Muscle Weakness in Critically Ill Patients
NCT02315339	Not specified	TERMINATED	European Home Mechanical Ventilation Registry
NCT02442986	Not specified	COMPLETED	Neurological Outcome in Surgical and Non-surgical Septic Patients
NCT02706314	Not specified	COMPLETED	Impact of Human Blood Serum From Critically Ill Patients on Human Colon Neuronal Networks.
NCT02765828	Not specified	COMPLETED	Identification of Tongue Involvement in Late-Onset Pompe Disease
NCT03042286	Not specified	UNKNOWN	SAPhIRE Statin Adverse Drug Reaction
NCT03141749	Not specified	COMPLETED	Venous Thromboembolism in DM1

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATORVASTATIN	4	1
PREDNISOLONE	4	1
UBIDECARENONE	3	1
VATIQUINONE	3	1
CHEMBL4587343	0	1
CHEMBL5272956	0	1