Hypertrophic cardiomyopathy

Summary

Hypertrophic cardiomyopathy (MONDO:0005045) is a disease caused by variants in ACTC1, FHOD3, MYBPC3, and 7 other genes, with 75 cohort genes (454 GWAS associations across 23 studies) and 227 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (15 cohort genes). Top therapeutic interventions include mavacamten, perhexiline, and diltiazem.

At a glance

• Causal genes: ACTC1 (GenCC Definitive), FHOD3 (GenCC Definitive), MYBPC3 (GenCC Definitive), MYH7 (GenCC Definitive) (+6 more)
• Cohort genes: 75
• GWAS associations: 454
• ClinVar variants: 13,277
• Clinical trials: 227

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy
Mondo ID	MONDO:0005045
EFO	EFO:0000538
MeSH	D002312
Orphanet	217569
DOID	DOID:11984
ICD-10-CM	I42.1, I42.2
ICD-11	1830681485
NCIT	C34449
SNOMED CT	233873004
UMLS	C0007194
MedGen	2881
MedDRA	10020871
Is cancer (heuristic)	no

Also known as: familial hypertrophic cardiomyopathy · hypertrophic cardiomyopathy · hypertrophic subaortic stenosis · obstructive hypertrophic cardiomyopathy

Data availability: 13,277 ClinVar variants · 127 ClinGen variant curations · 454 GWAS associations (23 studies) · 42 GenCC gene-disease records · 1 HPO phenotype · 120 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › hypertrophic cardiomyopathy

Related subtypes (5): myocarditis, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction

Subtypes (3): non-familial hypertrophic cardiomyopathy, progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome, familial hypertrophic cardiomyopathy

Genetics & variants

GWAS landscape

454 GWAS associations across 23 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs17617337	3e-67	BAG3	T	0.4
rs2234962	1e-49	BAG3	C	1.45
rs2644262	2e-46	FHOD3	C	0.31
rs3176326	9e-45	CDKN1A	A	0.34
rs5760054	5e-42	SMARCB1	C	0.32
rs1048302	1e-39	HSPB7	T	0.27
rs78310129	1e-38	OR5AK1P - OR5BQ1P	T	3.53
rs17099139	2e-38	BAG3	G	1.43
rs503274	3e-38	FHOD3	C	1.42
rs8033459	4e-33	SEC11A	T	0.24
rs79098768	2e-29	FBLIM1P2 - LINC02710	A	0.82
rs72840788	5e-29	BAG3	G	0.42
rs182427065	2e-28	OR5BD1P - CYCSP26	A	0.97
rs12210733	6e-28	SLC35F1 - CEP85L	A	0.44
rs28768976	2e-27	RPS26P8 - LINC02210	G	0.25
rs7210446	3e-26	PRKCA	A	0.22
rs1763606	5e-26	SRARP - HSPB7	A	0.29
rs617207	3e-25	FHOD3	A	0.43
rs549317738	3e-25	TRIM48 - TRIM51HP	A	57.18
rs764568652	3e-25	PRG3	G	65.26
rs2070458	6e-25	SMARCB1	A	1.3
rs187474069	2e-24	ARHGAP1	C	56.06
rs11196085	8e-24	VTI1A	C	0.22
rs4799426	4e-23	FHOD3	A	0.32
rs12212795	5e-22	SLC35F1 - CEP85L	C	1.51
rs10927886	2e-21	SRARP - HSPB7	G	1.27
rs4577128	3e-21	PRKCA	C	1.23
rs393838	5e-21	LINC02210, LINC02210-CRHR1	C	1.26
chr18:34280732	8e-21		C	1.01
rs2177843	3e-20	SYNPO2L, SYNPO2L-AS1	T	0.25

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011205	Tadros R	2021	1,733	6,628	Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.
GCST011211	Tadros R	2021	1,733	6,628	Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.
GCST90477899	Verma A	2024	715	450,257	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90296096	Ning C	2023	552	2,208	Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy.
GCST90477900	Verma A	2024	538	450,403	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90018861	Sakaue S	2021	507	489,220	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018641	Sakaue S	2021	383	177,745	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90132261	Gyftopoulos A	2022	305	0	Identification of Novel Genetic Variants and Comorbidities Associated With ICD-10-Based Diagnosis of Hypertrophic Cardiomyopathy Using the UK Biobank Cohort.
GCST90480147	Verma A	2024	275	121,450	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481987	Verma A	2024	275	121,450	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	5
rare (<0.01)	1
unknown	4

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	10
missense_variant	3
non_coding_transcript_exon_variant	2
3_prime_UTR_variant	1
unknown	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs17617337	10	119667372	C>T	0.21	intron_variant	BAG3	3e-67	Tier 4: intronic/intergenic
rs2234962	10	119670121	T>C,G	0.21	missense_variant	BAG3	1e-49	Tier 1: coding
rs2644262	18	36643603	T>C	0.288	intron_variant	FHOD3	2e-46	Tier 4: intronic/intergenic
rs3176326	6	36679512	G>A	0.212	intron_variant	CDKN1A	9e-45	Tier 4: intronic/intergenic
rs5760054	22	23819530	C>T	0.222	intron_variant	SMARCB1	5e-42	Tier 4: intronic/intergenic
rs1048302	1	16014384	T>A,C,G	0.326	3_prime_UTR_variant	HSPB7	1e-39	Tier 2: splice/UTR
rs78310129	11	57026403	C>T	0.01	intergenic_variant	OR5AK1P - OR5BQ1P	1e-38	Tier 4: intronic/intergenic
rs17099139	10	119659975	C>G,T	0.291	intron_variant	BAG3	2e-38	Tier 4: intronic/intergenic
rs503274	18	36673782	C>A,G,T	0.31	intron_variant	FHOD3	3e-38	Tier 4: intronic/intergenic
rs8033459	15	84710027	C>G,T	0.461	intron_variant	SEC11A	4e-33	Tier 4: intronic/intergenic
rs79098768	11	46176441	G>A,C	0.053	non_coding_transcript_exon_variant	FBLIM1P2 - LINC02710	2e-29	Tier 4: intronic/intergenic
rs72840788	10	119656173	G>A,T	0.208	intron_variant	BAG3	5e-29	Tier 4: intronic/intergenic
rs182427065	11	57985437	G>A,C	0.013	intron_variant	OR5BD1P - CYCSP26	2e-28	Tier 4: intronic/intergenic
rs12210733	6	118331912	G>A,C	0.055	intron_variant	SLC35F1 - CEP85L	6e-28	Tier 4: intronic/intergenic
rs28768976	17	45610951	A>G,T	0.234	intergenic_variant	RPS26P8 - LINC02210	2e-27	Tier 4: intronic/intergenic
rs7210446	17	66310896	G>A	0.426	intron_variant	PRKCA	3e-26	Tier 4: intronic/intergenic
rs1763606	1	16011787	A>C,G,T	0.327	intergenic_variant	SRARP - HSPB7	5e-26	Tier 4: intronic/intergenic
rs617207	18	36664879	A>G	0.291	intron_variant	FHOD3	3e-25	Tier 4: intronic/intergenic
rs549317738	11	55275284	C>A,G,T		intergenic_variant	TRIM48 - TRIM51HP	3e-25	Tier 4: intronic/intergenic
rs764568652	11	57380633	A>G		intron_variant	PRG3	3e-25	Tier 4: intronic/intergenic
rs2070458	22	23817120	A>C,T	0.22	intron_variant	SMARCB1	6e-25	Tier 4: intronic/intergenic
rs187474069	11	46689321	A>C		intron_variant	ARHGAP1	2e-24	Tier 4: intronic/intergenic
rs11196085	10	112745278	T>A,C,G	0.277	intron_variant	VTI1A	8e-24	Tier 4: intronic/intergenic
rs4799426	18	36700928	A>G	0.345	intron_variant	FHOD3	4e-23	Tier 4: intronic/intergenic
rs12212795	6	118333145	G>C	0.05	intron_variant	SLC35F1 - CEP85L	5e-22	Tier 4: intronic/intergenic
rs10927886	1	16012818	C>A,G	0.415	intergenic_variant	SRARP - HSPB7	2e-21	Tier 4: intronic/intergenic
rs4577128	17	66312355	T>A,C,G	0.43	intron_variant	PRKCA	3e-21	Tier 4: intronic/intergenic
rs393838	17	45628390	G>C,T	0.23	intron_variant	LINC02210, LINC02210-CRHR1	5e-21	Tier 4: intronic/intergenic
chr18:34280732				0.013			8e-21	Tier 4: intronic/intergenic
rs2177843	10	73650119	C>T	0.159	intron_variant	SYNPO2L, SYNPO2L-AS1	3e-20	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

327 uncertain significance, 184 likely benign, 35 conflicting classifications of pathogenicity, 28 pathogenic, 17 likely pathogenic, 4 pathogenic/likely pathogenic, 4 benign/likely benign, 1 benign/likely benign; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
10730	NM_000169.3(GLA):c.644A>G (p.Asn215Ser)	GLA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10768	NM_000169.3(GLA):c.640-801G>A	GLA	Pathogenic	criteria provided, multiple submitters, no conflicts
1075461	NM_000257.4(MYH7):c.4790T>C (p.Leu1597Pro)	LOC126861897	Pathogenic	criteria provided, single submitter
1027653	NM_000256.3(MYBPC3):c.2132G>A (p.Trp711Ter)	MYBPC3	Pathogenic	no assertion criteria provided
1067323	NM_000256.3(MYBPC3):c.1624+1G>T	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069672	NC_000011.9:g.(?47364119)(47374208_?)del	MYBPC3	Pathogenic	criteria provided, single submitter
1069713	NM_000256.3(MYBPC3):c.3688_3691dup (p.Ser1231fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1069832	NC_000011.9:g.(?_47353958)_47355505del	MYBPC3	Pathogenic	criteria provided, single submitter
1069833	NC_000011.9:g.(?47360865)(47369466_?)del	MYBPC3	Pathogenic	criteria provided, single submitter
1069890	NM_000256.3(MYBPC3):c.1730G>A (p.Trp577Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1069891	NM_000256.3(MYBPC3):c.1546G>T (p.Glu516Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1069892	NM_000256.3(MYBPC3):c.1420G>T (p.Glu474Ter)	MYBPC3	Pathogenic	criteria provided, single submitter
1069893	NM_000256.3(MYBPC3):c.1269_1282del (p.Ser424fs)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1070193	NM_000256.3(MYBPC3):c.514dup (p.Ile172fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1070637	NM_000256.3(MYBPC3):c.2012_2013insGG (p.Pro672fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1070911	NM_000256.3(MYBPC3):c.565del (p.Val189fs)	MYBPC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071502	NC_000011.10:g.47350113del	MYBPC3	Pathogenic	criteria provided, single submitter
1072518	NM_000256.3(MYBPC3):c.718_724del (p.Glu240fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1073146	NM_000256.3(MYBPC3):c.3424C>T (p.Gln1142Ter)	MYBPC3	Pathogenic	criteria provided, single submitter
1074065	NM_000256.3(MYBPC3):c.318del (p.Ala107fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1074099	NC_000011.10:g.47335210del	MYBPC3	Pathogenic	criteria provided, single submitter
1074339	NM_000256.3(MYBPC3):c.2164G>T (p.Glu722Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1074856	NM_000256.3(MYBPC3):c.1353del (p.Glu451fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1074858	NM_000256.3(MYBPC3):c.1048_1049del (p.Lys350fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1074948	NM_000256.3(MYBPC3):c.3357C>G (p.Tyr1119Ter)	MYBPC3	Pathogenic	criteria provided, single submitter
1075725	NC_000011.9:g.(?_47363401)_47367757del	MYBPC3	Pathogenic	criteria provided, single submitter
1075727	NC_000011.9:g.(?47357416)(47360310_?)del	MYBPC3	Pathogenic	criteria provided, single submitter
1076196	NM_000256.3(MYBPC3):c.405del (p.Ser137fs)	MYBPC3	Pathogenic	criteria provided, single submitter
1076719	NM_000256.3(MYBPC3):c.1831G>T (p.Glu611Ter)	MYBPC3	Pathogenic	criteria provided, multiple submitters, no conflicts
1076969	NM_000256.3(MYBPC3):c.1839del (p.Tyr614fs)	MYBPC3	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 218 · Orphanet: 148 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 6

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
ALPK3	ALPK3	GWAS, GenCC
FHOD3	FHOD3	GWAS, GenCC
TTN	TTN	GWAS, Orphanet
FLNC	FLNC	GWAS, Orphanet
PLN	PLN	GWAS, Orphanet
BAG3	BAG3	GWAS, Orphanet

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
ACTC1	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	12
ALPK3	Definitive	Autosomal recessive	cardiomyopathy, familial hypertrophic 27	7
DSP	Definitive	Autosomal dominant	arrhythmogenic cardiomyopathy with wooly hair and keratoderma	26
FHOD3	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	5
MYBPC3	Definitive	Autosomal dominant	hypertrophic cardiomyopathy 4	13
MYH7	Definitive	Autosomal dominant	hypertrophic cardiomyopathy 1	20
MYL3	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	4
RBM20	Definitive	Autosomal dominant	dilated cardiomyopathy	7
TNNC1	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	10
TNNI3	Definitive	Autosomal recessive	dilated cardiomyopathy 2A	11
JPH2	Strong	Autosomal recessive	cardiomyopathy, dilated, 2E	6
KLHL24	Strong	Autosomal recessive	cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies	12
LDB3	Strong	Autosomal recessive	cardiomyopathy, dilated, 2l	11
MYPN	Strong	Autosomal dominant	dilated cardiomyopathy	12
NEXN	Strong	Semidominant	dilated cardiomyopathy 1CC	5
TCAP	Strong	Autosomal dominant	hypertrophic cardiomyopathy 25	8
TRIM63	Strong	Autosomal recessive	hypertrophic cardiomyopathy	4
MT-TI	Moderate	Mitochondrial	hypertrophic cardiomyopathy
NEBL	Moderate	Autosomal dominant	dilated cardiomyopathy	2
RPS6KB1	Moderate	Autosomal dominant	hypertrophic cardiomyopathy	2
ANKRD1	Supportive	Autosomal dominant	familial isolated dilated cardiomyopathy	5
TMPO	Supportive	Autosomal dominant	familial isolated dilated cardiomyopathy	4
KLF10	Limited	Autosomal dominant	hypertrophic cardiomyopathy	2
LINC00598	Limited	Autosomal dominant	hypertrophic cardiomyopathy	2
MYLK2	Limited	Autosomal dominant	hypertrophic cardiomyopathy 1	4
MYOM1	Limited	Autosomal dominant	hypertrophic cardiomyopathy	2
OBSCN	Limited	Autosomal dominant	hypertrophic cardiomyopathy	3
PDLIM3	Limited	Autosomal dominant	hypertrophic cardiomyopathy
RYR2	Limited	Autosomal dominant	hypertrophic cardiomyopathy	8
SMYD1	Limited	Autosomal dominant	hypertrophic cardiomyopathy

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia
TCAP	Orphanet:154	Familial isolated dilated cardiomyopathy
TCAP	Orphanet:34514	Telethonin-related limb-girdle muscular dystrophy R7
TMPO	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNC1	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
JPH2	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:54260	Left ventricular noncompaction
ACTC1	Orphanet:99103	Atrial septal defect, ostium secundum type
LDB3	Orphanet:154	Familial isolated dilated cardiomyopathy
LDB3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LDB3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LDB3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LDB3	Orphanet:54260	Left ventricular noncompaction
LDB3	Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type
ANKRD1	Orphanet:154	Familial isolated dilated cardiomyopathy
MYPN	Orphanet:154	Familial isolated dilated cardiomyopathy
MYPN	Orphanet:171439	Childhood-onset nemaline myopathy
MYPN	Orphanet:171881	Cap myopathy
MYPN	Orphanet:75249	Familial isolated restrictive cardiomyopathy
KLHL24	Orphanet:508529	Intermediate epidermolysis bullosa simplex with cardiomyopathy
RBM20	Orphanet:154	Familial isolated dilated cardiomyopathy
NEXN	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome

Cohort genes → proteins

75 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	11
gwas_and_clinvar	4
multi_evidence	60

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALPK3	HGNC:17574	ENSG00000136383	Q96L96	Alpha-protein kinase 3	gwas,gencc,clinvar
FHOD3	HGNC:26178	ENSG00000134775	Q2V2M9	FH1/FH2 domain-containing protein 3	gwas,gencc,clinvar
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	gencc,clinvar
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	gencc,clinvar
TMPO	HGNC:11875	ENSG00000120802	P42166	Lamina-associated polypeptide 2, isoform alpha	gencc,clinvar
TNNC1	HGNC:11943	ENSG00000114854	P63316	Troponin C, slow skeletal and cardiac muscles	gencc,clinvar
TNNI3	HGNC:11947	ENSG00000129991	P19429	Troponin I, cardiac muscle	gencc,clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	gwas,clinvar
JPH2	HGNC:14202	ENSG00000149596	Q9BR39	Junctophilin-2	gencc,clinvar
ACTC1	HGNC:143	ENSG00000159251	P68032	Actin, alpha cardiac muscle 1	gencc,clinvar
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	gencc,clinvar
ANKRD1	HGNC:15819	ENSG00000148677	Q15327	Ankyrin repeat domain-containing protein 1	gencc,clinvar
TRIM63	HGNC:16007	ENSG00000158022	Q969Q1	E3 ubiquitin-protein ligase TRIM63	gencc,clinvar
MYLK2	HGNC:16243	ENSG00000101306	Q9H1R3	Myosin light chain kinase 2, skeletal/cardiac muscle	gencc,clinvar
NEBL	HGNC:16932	ENSG00000078114	O76041	Nebulette	gencc,clinvar
CALR3	HGNC:20407	ENSG00000269058	Q96L12	Calreticulin-3	gencc,clinvar
PDLIM3	HGNC:20767	ENSG00000154553	Q53GG5	PDZ and LIM domain protein 3	gencc,clinvar
MYPN	HGNC:23246	ENSG00000138347	Q86TC9	Myopalladin	gencc,clinvar
KLHL24	HGNC:25947	ENSG00000114796	Q6TFL4	Kelch-like protein 24	gencc,clinvar
RBM20	HGNC:27424	ENSG00000203867	Q5T481	RNA-binding protein 20	gencc,clinvar
NEXN	HGNC:29557	ENSG00000162614	Q0ZGT2	Nexilin	gencc,clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	gencc,clinvar
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	gwas,clinvar
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	gencc,clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	gencc,clinvar
MYL3	HGNC:7584	ENSG00000160808	P08590	Myosin light chain 3	gencc,clinvar
MYOM1	HGNC:7613	ENSG00000101605	P52179	Myomesin-1	gencc,clinvar
PLN	HGNC:9080	ENSG00000198523	P26678	Phospholamban	gwas,clinvar
BAG3	HGNC:939	ENSG00000151929	O95817	BAG family molecular chaperone regulator 3	gwas,clinvar
RPS6KB1	HGNC:10436	ENSG00000108443	P23443	Ribosomal protein S6 kinase beta-1	gencc
SRI	HGNC:11292	ENSG00000075142	P30626	Sorcin	gencc
KLF10	HGNC:11810	ENSG00000155090	Q13118	Krueppel-like factor 10	gencc
TNNC2	HGNC:11944	ENSG00000101470	P02585	Troponin C, skeletal muscle	gencc
OBSCN	HGNC:15719	ENSG00000154358	Q5VST9	Obscurin	gencc
SMYD1	HGNC:20986	ENSG00000115593	Q8NB12	Histone-lysine N-methyltransferase SMYD1	gencc
TTL	HGNC:21586	ENSG00000114999	Q8NG68	Tubulin–tyrosine ligase	gencc
LINC00598	HGNC:42770	ENSG00000215483		long intergenic non-protein coding RNA 598	gencc
MT-TI	HGNC:7488	ENSG00000210100		mitochondrially encoded tRNA-Ile (AUU/C)	gencc
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar
SGCA	HGNC:10805	ENSG00000108823	Q16586	Alpha-sarcoglycan	clinvar
SGCB	HGNC:10806	ENSG00000163069	Q16585	Beta-sarcoglycan	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
SLC25A4	HGNC:10990	ENSG00000151729	P12235	ADP/ATP translocase 1	clinvar
SLC6A6	HGNC:11052	ENSG00000131389	P31641	Sodium- and chloride-dependent taurine transporter	gwas
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	gwas
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	clinvar
SSPN	HGNC:11322	ENSG00000123096	Q14714	Sarcospan	gwas
STRN	HGNC:11424	ENSG00000115808	O43815	Striatin	gwas
SVIL	HGNC:11480	ENSG00000197321	O95425	Supervillin	clinvar
TBX1	HGNC:11592	ENSG00000184058	O43435	T-box transcription factor TBX1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALPK3	Alpha-protein kinase 3	Involved in cardiomyocyte differentiation.
FHOD3	FH1/FH2 domain-containing protein 3	Actin-organizing protein that may cause stress fiber formation together with cell elongation.
RYR2	Ryanodine receptor 2	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 cardiac muscle contraction.
TCAP	Telethonin	Muscle assembly regulating factor.
TMPO	Lamina-associated polypeptide 2, isoform alpha	May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly.
TNNC1	Troponin C, slow skeletal and cardiac muscles	Troponin is the central regulatory protein of striated muscle contraction.
TNNI3	Troponin I, cardiac muscle	Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
JPH2	Junctophilin-2	Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes.
ACTC1	Actin, alpha cardiac muscle 1	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
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.
ANKRD1	Ankyrin repeat domain-containing protein 1	May play an important role in endothelial cell activation.
TRIM63	E3 ubiquitin-protein ligase TRIM63	E3 ubiquitin ligase.
MYLK2	Myosin light chain kinase 2, skeletal/cardiac muscle	Implicated in the level of global muscle contraction and cardiac function.
NEBL	Nebulette	Binds to actin and plays an important role in the assembly of the Z-disk.
CALR3	Calreticulin-3	During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3.
PDLIM3	PDZ and LIM domain protein 3	May play a role in the organization of actin filament arrays within muscle cells.
MYPN	Myopalladin	Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.
KLHL24	Kelch-like protein 24	Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity.
RBM20	RNA-binding protein 20	RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH.
NEXN	Nexilin	Involved in regulating cell migration through association with the actin cytoskeleton.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
MYBPC3	Myosin-binding protein C, cardiac-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
MYL3	Myosin light chain 3	Regulatory light chain of myosin.
MYOM1	Myomesin-1	Major component of the vertebrate myofibrillar M band.
PLN	Phospholamban	Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+).
BAG3	BAG family molecular chaperone regulator 3	Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g.
RPS6KB1	Ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
SRI	Sorcin	Calcium-binding protein that modulates excitation-contraction coupling in the heart.
KLF10	Krueppel-like factor 10	Transcriptional repressor which binds to the consensus sequence 5’-GGTGTG-3'.
TNNC2	Troponin C, skeletal muscle	Troponin is the central regulatory protein of striated muscle contraction.
OBSCN	Obscurin	Structural component of striated muscles which plays a role in myofibrillogenesis.
SMYD1	Histone-lysine N-methyltransferase SMYD1	Methylates histone H3 at ‘Lys-4’ (H3K4me), seems able to perform both mono-, di-, and trimethylation.
TTL	Tubulin–tyrosine ligase	Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin.
SCN5A	Sodium channel protein type 5 subunit alpha	Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SGCA	Alpha-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
SGCB	Beta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SLC25A4	ADP/ATP translocase 1	ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell.
SLC6A6	Sodium- and chloride-dependent taurine transporter	Mediates sodium- and chloride-dependent transport of taurine.
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
SSPN	Sarcospan	Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix.
STRN	Striatin	Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.
SVIL	Supervillin	Forms a high-affinity link between the actin cytoskeleton and the membrane.
TBX1	T-box transcription factor TBX1	Transcription factor that plays a key role in cardiovascular development by promoting pharyngeal arch segmentation during embryonic development.
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
TCF7L2	Transcription factor 7-like 2	Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner.

Protein-family classification

Druggable: 22 · Difficult: 19 · Unknown: 34 · 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
Ion channel	4	6.0×	0.042
Scaffold/PPI	9	2.1×	0.129
Kinase	6	2.2×	0.160
Antibody/Immunoglobulin	5	1.9×	0.257
Transcription factor	10	1.1×	0.764
Protease	2	1.0×	0.786
GPCR	3	1.0×	0.786
Other/Unknown	34	0.8×	0.989
Enzyme (other)	2	0.3×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALPK3	Kinase	yes		Ig_sub2, Ig_sub, a-kinase_dom
FHOD3	Other/Unknown	no		ARM-like, DAD_dom, GBD/FH3_dom
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf
TMPO	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, LEM-like_dom
TNNC1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
TNNI3	Other/Unknown	no		Troponin, Troponin-I_N, Troponin_sf
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
JPH2	Other/Unknown	no		MORN, Junctophilin
ACTC1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
ANKRD1	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
TRIM63	Transcription factor	no		Znf_B-box, Znf_RING, Znf_RING/FYVE/PHD
MYLK2	Kinase	yes	2.7.11.18	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
NEBL	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulette_SH3
CALR3	Other/Unknown	no		Calret/calnex, Calreticulin/calnexin_P_dom_sf, Calreticulin
PDLIM3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
MYPN	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
KLHL24	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf
RBM20	Transcription factor	no		RRM_dom, Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2
NEXN	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_I-set
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
MYL3	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, CALM/Myosin/TropC-like
MYOM1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
PLN	Other/Unknown	no		PLB
BAG3	Scaffold/PPI	no		WW_dom, BAG_domain, WW_dom_sf
RPS6KB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
SRI	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
KLF10	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
TNNC2	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
OBSCN	Kinase	yes		IQ_motif_EF-hand-BS, DH_dom, Prot_kinase_dom
SMYD1	Transcription factor	no		SET_dom, Znf_MYND, TPR-like_helical_dom_sf
TTL	Enzyme (other)	yes	6.3.2.25	TTL/TTLL_fam, Tubulin-tyrosine_ligase
LINC00598	Other/Unknown	no
MT-TI	Other/Unknown	no
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
SGCA	Other/Unknown	no		Cadg, Sarcoglycan_alpha/epsilon, Cadherin-like_sf
SGCB	Other/Unknown	no		Sarcoglycan, Sgcb
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SLC25A4	Other/Unknown	no		MCP, ADT_euk_type, MCP_transmembrane
SLC6A6	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_taurine, SNS_sf
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
SSPN	Other/Unknown	no		CD20-like_TM, Sarcospan
STRN	Scaffold/PPI	no		WD40_rpt, Striatin_N, WD40/YVTN_repeat-like_dom_sf
SVIL	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
TBX1	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	1
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	18
apex of heart	17
left ventricle myocardium	13
skeletal muscle tissue of rectus abdominis	12
gastrocnemius	11
heart right ventricle	10
myocardium	8
gluteal muscle	6
skeletal muscle tissue of biceps brachii	6
right atrium auricular region	5
buccal mucosa cell	5
colonic epithelium	5
tibialis anterior	4
cardiac atrium	4
vastus lateralis	4
endothelial cell	4
ventricular zone	3
ganglionic eminence	3
cortical plate	3
heart left ventricle	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALPK3	201	broad	yes	gastrocnemius, hindlimb stylopod muscle, gluteal muscle
FHOD3	244	ubiquitous	marker	apex of heart, left ventricle myocardium, ventricular zone
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
TMPO	287	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo
TNNC1	207	broad	marker	triceps brachii, gluteal muscle, heart right ventricle
TNNI3	169	broad	marker	apex of heart, left ventricle myocardium, right atrium auricular region
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
JPH2	173	broad	yes	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, tibialis anterior
ACTC1	224	broad	marker	left ventricle myocardium, heart right ventricle, myocardium
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
ANKRD1	155	ubiquitous	marker	apex of heart, right atrium auricular region, cardiac atrium
TRIM63	169	tissue_specific	marker	gastrocnemius, tibialis anterior, hindlimb stylopod muscle
MYLK2	148	tissue_specific	yes	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gastrocnemius
NEBL	282	broad	marker	heart right ventricle, myocardium, cranial nerve II
CALR3	57	broad	yes	right testis, left testis, testis
PDLIM3	264	ubiquitous	marker	gluteal muscle, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii
MYPN	116	broad	marker	hindlimb stylopod muscle, gastrocnemius, vastus lateralis
KLHL24	289	ubiquitous	marker	endothelial cell, blood vessel layer, buccal mucosa cell
RBM20	191	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
NEXN	229	ubiquitous	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, myocardium
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
MYBPC3	149	tissue_specific	marker	apex of heart, right atrium auricular region, cardiac atrium
MYH7	167	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii
MYL3	198	broad	marker	apex of heart, heart right ventricle, hindlimb stylopod muscle
MYOM1	215	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gluteal muscle
PLN	243	broad	marker	heart right ventricle, myocardium, left ventricle myocardium
BAG3	286	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, body of tongue
RPS6KB1	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 168.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
RPS6KB1	5,474
SMARCB1	5,083
BAG3	4,957
TTR	4,528
VCL	4,495
TTN	4,237
UQCRC1	4,109
TXNRD1	4,072
TCF7L2	3,775

Intra-cohort edges

A	B	Sources
ACTC1	MYBPC3	intact
ACTC1	SMARCB1	intact
ACTN2	CACNA1C	biogrid_interaction
ACTN2	LDB3	biogrid_interaction, intact, string_interaction
ACTN2	MYH7	biogrid_interaction, string_interaction
ACTN2	MYOM1	string_interaction
ACTN2	MYOZ2	biogrid_interaction, intact, string_interaction
ACTN2	MYPN	biogrid_interaction, string_interaction
ACTN2	NEBL	string_interaction
ACTN2	NEXN	string_interaction
ACTN2	PDLIM3	biogrid_interaction, intact, string_interaction
ACTN2	TCAP	string_interaction
ACTN2	TNNC2	string_interaction
ACTN2	TNNT2	string_interaction
ACTN2	TPM1	biogrid_interaction, string_interaction
ACTN2	TTN	string_interaction
ACTN2	VCL	string_interaction
ALPK3	MYBPC3	string_interaction
ALPK3	MYH7	string_interaction
ALPK3	MYL3	string_interaction
ALPK3	TNNT2	string_interaction
ANKRD1	MYPN	biogrid_interaction, string_interaction
ANKRD1	NEBL	string_interaction
ANKRD1	TCAP	string_interaction
ANKRD1	TRIM63	biogrid_interaction
ANKRD1	TTN	biogrid_interaction, string_interaction
BAG3	FLNC	string_interaction
BAG3	LDB3	string_interaction
BRAF	SOS1	string_interaction
BRAF	TBX3	intact
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	CAV3	string_interaction
CACNA1C	HCN4	string_interaction
CACNA1C	JPH2	string_interaction
CACNA1C	RYR2	biogrid_interaction, string_interaction
CACNB2	HCN4	string_interaction
CACNB2	SCN5A	string_interaction
CALR3	JPH2	string_interaction
CALR3	MYL3	string_interaction
CALR3	MYLK2	string_interaction
CALR3	MYOZ2	string_interaction
CALR3	MYPN	string_interaction
CALR3	RYR2	string_interaction
CALR3	TCAP	string_interaction
CAV3	JPH2	string_interaction
CAV3	SCN5A	string_interaction
CAV3	SSPN	string_interaction
FHOD3	RBM20	string_interaction
FHOD3	TTN	string_interaction
FLNC	LDB3	string_interaction

Structural data

PDB: 49 · AlphaFold-only: 24 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTR	P02766	462
BRAF	P15056	131
SOS1	Q07889	91
TTN	Q8WZ42	64
TNNC1	P63316	61
SLC6A6	P31641	45
MYH7	P12883	43
TNNI3	P19429	39
VCL	P18206	37
CACNA1C	Q13936	33
CASR	P41180	31
RYR2	Q92736	26
OBSCN	Q5VST9	25
TNNT2	P45379	25
RPS6KB1	P23443	22
NSD2	O96028	22
MYBPC3	Q14896	17
SMARCB1	Q12824	17
ACTC1	P68032	16
SCN5A	Q14524	16
ACTN2	P35609	16
TMPO	P42166	14
FLNC	Q14315	14
TPM1	P09493	14
TGFB3	P10600	11
MYOM1	P52179	9
TXNRD1	Q16881	9
HCN4	Q9Y3Q4	8
PLN	P26678	7
SRI	P30626	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SMYD1	Q8NB12	93.07
SLC25A4	P12235	92.07
CAV3	P56539	88.54
KLHL24	Q6TFL4	87.69
OR9Q1	Q8NGQ5	84.62
OR5AK2	Q8NH90	84.16
ANKRD1	Q15327	82.64
GTPBP3	Q969Y2	82.25
SGCA	Q16586	80.15
USP3	Q9Y6I4	79.40
CALR3	Q96L12	77.43
SGCB	Q16585	76.67
SSPN	Q14714	74.41
MYH7B	A7E2Y1	73.79
NEXN	Q0ZGT2	70.78
STRN	O43815	68.70
PDLIM3	Q53GG5	66.98
MYOZ2	Q9NPC6	65.51
FHOD3	Q2V2M9	64.62
BAG3	O95817	57.98
MYPN	Q86TC9	52.71
ALPK3	Q96L96	49.15
RBM20	Q5T481	48.52
TRDN	Q13061	47.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 602. Enrichment computed across 185 evidence-associated genes (125 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 125 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	15	37.0×	8e-18	TCAP, TNNC1, TNNI3, TTN, ACTC1, MYBPC3, MYL3, TNNC2 (+7 more)
Muscle contraction	19	11.7×	5e-13	RYR2, TCAP, ACTC1, MYBPC3, MYL3, SCN5A, SRI, CACNA1C (+11 more)
Formation of the dystrophin-glycoprotein complex (DGC)	8	19.8×	1e-06	ACTC1, SGCA, SGCB, SSPN, DMD, DTNA, LAMA2, LAMA4
Non-integrin membrane-ECM interactions	10	12.3×	1e-06	ACTC1, SGCA, SGCB, SSPN, TTR, COL1A1, DMD, LAMA2 (+2 more)
Cardiac conduction	11	9.6×	2e-06	RYR2, SCN5A, SRI, CACNA1C, CACNB2, AKAP9, ABCC9, KCNE1 (+3 more)
Phase 2 - plateau phase	5	30.4×	4e-05	CACNA1C, CACNB2, AKAP9, KCNE1, KCNQ1
Ion homeostasis	7	11.4×	2e-04	RYR2, TNNI3, PLN, SRI, TRDN, DMPK, ABCC9
Phase 3 - rapid repolarisation	4	36.5×	2e-04	AKAP9, KCNE1, KCNH2, KCNQ1
Depolymerization of the Nuclear Lamina	4	24.4×	0.001	TMPO, EMD, LMNA, PRKCA
Inwardly rectifying K+ channels	4	22.8×	0.001	ABCC9, KCNJ2, KCNJ5, KCNJ8
Nuclear Envelope Breakdown	4	14.6×	0.008	TMPO, EMD, LMNA, PRKCA
Extracellular matrix organization	9	4.5×	0.008	ACTC1, SGCA, SGCB, SSPN, TGFB3, LAMA2, LAMA4, MMP11 (+1 more)
Regulation of CDH1 Function	3	22.8×	0.012	ACTC1, VCL, JUP
Potassium Channels	6	6.5×	0.014	ABCC9, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1
Neuronal System	10	3.5×	0.021	CACNB2, ACTN2, ABCC9, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1 (+2 more)
ATP sensitive Potassium channels	2	45.7×	0.026	ABCC9, KCNJ8
Signaling by BRAF and RAF1 fusions	5	6.8×	0.029	BRAF, VCL, AKAP9, LMNA, MAP2K2
Signalling to ERKs	3	14.4×	0.035	BRAF, SOS1, MAP2K2
Initiation of Nuclear Envelope (NE) Reformation	3	14.4×	0.035	TMPO, EMD, LMNA
Oncogenic MAPK signaling	4	7.9×	0.047	BRAF, AKAP9, LMNA, MAP2K2
Diseases of signal transduction by growth factor receptors and second messengers	8	3.6×	0.047	BRAF, SOS1, STRN, TCF7L2, AKAP9, KIF5B, LMNA, MAP2K2
Negative feedback regulation of MAPK pathway	2	30.4×	0.047	BRAF, MAP2K2
Signaling by PDGFR in disease	2	26.1×	0.063	SOS1, STRN
Prolonged ERK activation events	2	22.8×	0.074	BRAF, MAP2K2
Cardiogenesis	3	10.2×	0.074	TBX1, SMYD1, NKX2-5
Formation of the cornified envelope	6	4.2×	0.074	DSP, DSC2, DSC3, DSG2, JUP, PKP2
MET activates PTK2 signaling	3	9.1×	0.093	COL1A1, LAMA2, LAMA4
MAPK1 (ERK2) activation	2	18.3×	0.098	MAP2K2, PTPN11
G protein gated Potassium channels	2	18.3×	0.098	KCNJ2, KCNJ5
EGFR Transactivation by Gastrin	2	18.3×	0.098	SOS1, PRKCA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 164 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cardiac muscle contraction	21	51.4×	9e-29	RYR2, TCAP, TNNC1, TNNI3, TTN, ACTC1, MYLK2, MYBPC3 (+13 more)
sarcomere organization	17	39.7×	1e-20	FHOD3, TCAP, TTN, LDB3, ANKRD1, MYPN, FLNC, MYBPC3 (+9 more)
regulation of heart rate by cardiac conduction	17	38.8×	1e-20	DSP, SCN5A, CACNA1C, CACNB2, HCN4, TRPM4, DSC2, DSG2 (+9 more)
ventricular cardiac muscle tissue morphogenesis	10	42.8×	3e-12	TNNC1, TNNI3, MYBPC3, MYH7, MYL3, TNNT2, TPM1, MYH6 (+2 more)
ventricular cardiac muscle cell action potential	9	54.4×	4e-12	RYR2, SCN5A, CAV3, GPD1L, ANK2, KCNE1, KCNH2, KCNQ1 (+1 more)
regulation of ventricular cardiac muscle cell action potential	8	68.5×	7e-12	RYR2, DSP, CACNA1C, TRPM4, DSC2, DSG2, JUP, PKP2
muscle filament sliding	8	51.4×	2e-10	TCAP, TNNC1, TNNI3, TTN, MYH7, TNNT2, TPM1, MYH6
muscle contraction	13	16.5×	2e-10	TTN, TRIM63, MYH7, MYL3, SGCA, SSPN, TRDN, HCN4 (+5 more)
regulation of heart rate	10	28.5×	2e-10	RYR2, MYH7, SCN5A, CAV3, HCN4, GPD1L, DMD, ANK2 (+2 more)
cardiac myofibril assembly	7	55.3×	2e-09	FHOD3, TCAP, TTN, ACTC1, ADPRHL1, CSRP3, MYL2
heart morphogenesis	10	22.8×	2e-09	MYBPC3, TBX1, FKRP, SYNPO2L, NKX2-5, NIPBL, DLC1, GAA (+2 more)
regulation of heart contraction	9	27.2×	3e-09	PLN, TNNT2, TPM1, CAV3, DES, DMPK, HSPB7, KCNQ1 (+1 more)
regulation of cardiac muscle cell contraction	7	48.0×	5e-09	MYBPC3, PLN, SCN5A, SRI, MYH7B, ANK2, KCNJ2
regulation of the force of heart contraction	7	42.3×	1e-08	MYH7, MYL3, PLN, CSRP3, GAA, MYH6, MYL2
cardiac muscle cell development	8	30.4×	1e-08	ALPK3, TCAP, TTN, SGCB, CAV3, ACTN2, NKX2-5, MYH6
muscle organ development	12	12.2×	2e-08	SGCA, SGCB, TBX1, CAV3, CRYAB, CTF1, DMD, EMD (+4 more)
regulation of ventricular cardiac muscle cell membrane repolarization	7	36.0×	4e-08	SCN5A, CAV3, AKAP9, ANK2, KCNE1, KCNH2, KCNQ1
cardiac muscle tissue morphogenesis	6	51.4×	5e-08	TCAP, TTN, ACTC1, ANKRD1, MYLK2, NKX2-5
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	5	73.4×	1e-07	DSP, DSC2, DSG2, JUP, PKP2
heart development	15	7.2×	2e-07	ALPK3, TNNI3, LDB3, PDLIM3, TBX1, TGFB3, CACNA1C, SMYD1 (+7 more)
muscle cell cellular homeostasis	7	27.7×	3e-07	PLN, BAG3, CSRP3, DMD, FXN, GAA, LAMP2
regulation of cardiac muscle contraction	6	32.5×	1e-06	RYR2, CAV3, HCN4, NKX2-5, RNF207, ANK2
cardiac muscle hypertrophy	5	51.4×	1e-06	RYR2, TCAP, TTN, CAV3, CSRP3
striated muscle contraction	6	30.8×	2e-06	RYR2, TTN, MYLK2, MYH7, DTNA, MYH6
membrane depolarization during AV node cell action potential	4	82.2×	2e-06	SCN5A, CACNA1C, CACNB2, TRPM4
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	6	24.7×	6e-06	RYR2, PLN, TRDN, CACNA1C, DMD, ANK2
potassium ion import across plasma membrane	7	15.6×	1e-05	HCN4, ABCC9, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1
detection of muscle stretch	4	58.7×	1e-05	TCAP, TTN, CAV3, CSRP3
positive regulation of potassium ion transmembrane transport	5	30.2×	2e-05	FHL1, KCNE1, KCNH2, KCNJ2, KCNQ1
skeletal muscle contraction	6	18.7×	3e-05	TCAP, TNNC1, TNNI3, TTN, MYH7, TNNC2

Therapeutics

Drugs indicated for this disease

1 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Mavacamten	Approved (phase 4)
Aficamten	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Perhexiline	Phase 3 (in late-stage trials)
Sotagliflozin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Amlodipine, Candesartan, Diltiazem, Eleclazine, Losartan, Pirfenidone, Sacubitril, Trientine, Trimetazidine, Valsartan.

Drug target analysis

Approved (phase 4): 14 · Phase ≥3: 15 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 85 of 185 evidence-associated genes (46%) 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
TNNC1	FINGOLIMOD
MYLK2	FEDRATINIB
RPS6KB1	FEDRATINIB
KLF10	TOLCAPONE
SCN5A	BEPRIDIL
BRAF	VEMURAFENIB
SOS1	IDARUBICIN
TTR	TRICLABENDAZOLE
TXNRD1	METHYLENE BLUE ANHYDROUS
NSD2	VENETOCLAX
CACNA1C	REMIFENTANIL
CACNB2	NIMODIPINE
CASR	CINACALCET HYDROCHLORIDE
HCN4	IVABRADINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN5A	108	4
CACNA1C	85	4
BRAF	48	4
RPS6KB1	39	4
TTR	29	4
MYLK2	19	4
CASR	10	4
NSD2	8	4
SOS1	5	4
TXNRD1	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FINGOLIMOD	4	TNNC1
FEDRATINIB	4	BRAF, MYLK2, RPS6KB1, SCN5A
AXITINIB	4	MYLK2
SORAFENIB	4	BRAF, MYLK2, RPS6KB1
PAZOPANIB	4	BRAF, MYLK2
NINTEDANIB	4	MYLK2, RPS6KB1, SCN5A
SUNITINIB	4	CACNA1C, MYLK2, RPS6KB1, SCN5A
DASATINIB	4	BRAF, CACNA1C, MYLK2, SCN5A, TTR
ERLOTINIB	4	BRAF, MYLK2
GEFITINIB	4	BRAF, MYLK2
VANDETANIB	4	RPS6KB1
BOSUTINIB	4	RPS6KB1
CRIZOTINIB	4	RPS6KB1
MIDOSTAURIN	4	RPS6KB1
TOLCAPONE	4	KLF10, TTR
ATOMOXETINE	4	KLF10
BEPRIDIL	4	CACNA1C, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	CACNA1C, SCN5A
IMIPRAMINE	4	CACNA1C, SCN5A
DROPERIDOL	4	CACNA1C, SCN5A
PONATINIB	4	BRAF, SCN5A
DULOXETINE	4	CACNA1C, SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
RPS6KB1	585	Binding:582, Functional:2, ADMET:1
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
TTR	423	Binding:391, Functional:32
SOS1	421	Binding:409, Functional:12
NSD2	264	Binding:256, Functional:8
MYLK2	196	Binding:196
TXNRD1	131	Binding:116, Functional:15
CASR	45	Functional:32, Binding:13
HCN4	30	Binding:20, ADMET:5, Functional:4, Toxicity:1
TCF7L2	22	Binding:22
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
RYR2	15	Binding:15
ALPK3	10	Binding:10
KLF10	10	Binding:10
TNNC1	8	Binding:8
BAG3	8	Binding:8
TMPO	7	Binding:7
SMARCB1	7	Binding:7
ACTC1	6	Binding:6
SLC6A6	5	Binding:4, Functional:1
SMYD1	3	Binding:3
TTL	3	Binding:3
TPM1	3	Binding:3
USP3	3	Binding:3
TNNI3	2	Binding:2
DSP	2	Binding:2
TNNT2	2	Binding:2
VCL	2	Binding:2
TTN	1	Binding:1
SRI	1	Binding:1
SLC25A4	1	Binding:1
TGFB3	1	Binding:1
UQCRC1	1	Binding:1
PRDM11	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase
MYLK2	2.7.11.18	myosin-light-chain kinase
RPS6KB1	2.7.11.1	non-specific serine/threonine protein kinase
TTL	6.3.2.25	tubulin-tyrosine ligase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TXNRD1	1.8.1.9	thioredoxin-disulfide reductase (NADPH)
NSD2	2.1.1.356, 2.1.1.357, 2.1.1.359	[histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine36 N-dimethyltransferase, [histone H3]-lysine36 N-trimethyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MYLK2	196
RPS6KB1	585
SCN5A	594
BRAF	1,442
SOS1	421
TTR	423
TXNRD1	131
NSD2	264
CACNA1C	575

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

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)
FINGOLIMOD	4	TNNC1
FEDRATINIB	4	BRAF, MYLK2, RPS6KB1, SCN5A
AXITINIB	4	MYLK2
SORAFENIB	4	BRAF, MYLK2, RPS6KB1
PAZOPANIB	4	BRAF, MYLK2
NINTEDANIB	4	MYLK2, RPS6KB1, SCN5A
SUNITINIB	4	CACNA1C, MYLK2, RPS6KB1, SCN5A
DASATINIB	4	BRAF, CACNA1C, MYLK2, SCN5A, TTR
ERLOTINIB	4	BRAF, MYLK2
GEFITINIB	4	BRAF, MYLK2
VANDETANIB	4	RPS6KB1
BOSUTINIB	4	RPS6KB1
CRIZOTINIB	4	RPS6KB1
MIDOSTAURIN	4	RPS6KB1
TOLCAPONE	4	KLF10, TTR
ATOMOXETINE	4	KLF10
BEPRIDIL	4	CACNA1C, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	CACNA1C, SCN5A
IMIPRAMINE	4	CACNA1C, SCN5A
DROPERIDOL	4	CACNA1C, SCN5A
PONATINIB	4	BRAF, SCN5A
DULOXETINE	4	CACNA1C, SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	14	TNNC1, MYLK2, RPS6KB1, KLF10, SCN5A, BRAF, SOS1, TTR, TXNRD1, NSD2 (+4 more)
B	Phased (≥1) drug, not yet approved	2	RYR2, SLC6A6
C	Druggable family + PDB, no drug	7	TTN, FLNC, MYBPC3, MYOM1, OBSCN, TTL, UQCRC1
D	Druggable family + AlphaFold only, no drug	6	ALPK3, MYPN, NEXN, USP3, OR9Q1, OR5AK2
E	Difficult family or no structure, no drug	46	FHOD3, TCAP, TMPO, TNNI3, JPH2, ACTC1, LDB3, ANKRD1, TRIM63, NEBL (+36 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
JPH2	0	RYR2
SRI	1	RYR2
TRDN	0	RYR2
ALPK3	10	—
FHOD3	0	—
TCAP	0	—
TMPO	7	—
TNNI3	2	—
TTN	1	—
ACTC1	6	—
LDB3	0	—
ANKRD1	0	—
TRIM63	0	—
NEBL	0	—
CALR3	0	—
PDLIM3	0	—
MYPN	0	—
KLHL24	0	—
RBM20	0	—
NEXN	0	—
DSP	2	—
FLNC	0	—
MYBPC3	0	—
MYH7	0	—
MYL3	0	—
MYOM1	0	—
PLN	0	—
BAG3	8	—
TNNC2	0	—
OBSCN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 227.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	165
PHASE2	23
PHASE3	14
PHASE1	10
PHASE4	8
PHASE2/PHASE3	4
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00319982	PHASE2/PHASE3	COMPLETED	Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02291237	PHASE2/PHASE3	TERMINATED	Effect of Eleclazine (GS-6615) on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT03723655	PHASE2/PHASE3	COMPLETED	A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed MAVERICK-HCM or EXPLORER-HCM
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05366101	PHASE2/PHASE3	COMPLETED	Lifestyle and Pharmacological Interventions in Hypertrophic Cardiomyopathy
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT05836259	PHASE1/PHASE2	RECRUITING	Multi-center, Open-label, Single-ascending Dose Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM
NCT06347159	PHASE2	ACTIVE_NOT_RECRUITING	A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM)
NCT06516068	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07021963	PHASE2	RECRUITING	A Clinical Study to Evaluate the Long-term Safety of HRS-1893 in Hypertrophic Cardiomyopathy
NCT07367724	PHASE2	RECRUITING	Ademetionine in Obstructive Hypertrophic Cardiomyopathy
NCT07464132	PHASE1/PHASE2	RECRUITING	Application of [68Ga]Ga-NI-FAPI-04 PET/CT Imaging in Fibroblast Activation Protein Related Diseases
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MAVACAMTEN	4	22
PERHEXILINE	4	9
DILTIAZEM	4	6
BISOPROLOL	4	3
METOPROLOL	4	3
REGADENOSON ANHYDROUS	4	2
SACUBITRIL	4	2
SPIRONOLACTONE	4	2
TRIMETAZIDINE	4	2
ADENOSINE	4	1
CARVEDILOL	4	1
EMPAGLIFLOZIN	4	1
MANGAFODIPIR TRISODIUM	4	1
PIRFENIDONE	4	1
RANOLAZINE	4	1
TRIENTINE	4	1
VERAPAMIL	4	1
AFICAMTEN	3	5
ADEMETIONINE	3	1
CANDESARTAN	3	1
ELECLAZINE	3	1
DEXVERAPAMIL	2	1
CHEMBL1562223	0	2
CHEMBL30458	0	2
CHEMBL4303537	0	1
CHEMBL606298	0	1
CHEMBL5177502	0	1
(R)-Carvedilol	0	1