Familial dilated cardiomyopathy

Summary

Familial dilated cardiomyopathy (MONDO:0016333) is a disease (an umbrella term covering 29 Mondo subtypes) with 40 cohort genes and 9 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (8 cohort genes). Top therapeutic interventions include doxazosin, carvedilol, and metoprolol succinate.

At a glance

• Umbrella term: 29 Mondo subtypes
• Cohort genes: 40
• ClinVar variants: 214
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial dilated cardiomyopathy
Mondo ID	MONDO:0016333
MeSH	C536231
OMIM	115200
Orphanet	217607
ICD-11	423719003
UMLS	C0340427
MedGen	90951
GARD	0020525
Is cancer (heuristic)	no

Also known as: DCM · dilated cardiomyopathy, familial · hereditary dilated cardiomyopathy · hypokinetic dilated cardiomyopathy, familial · idiopathic dilated cardiomyopathy

Data availability: 214 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 29 Mondo subtypes.

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

Related subtypes (2): viral dilated cardiomyopathy, non-familial dilated cardiomyopathy

Subtypes (29): autosomal recessive limb-girdle muscular dystrophy type 2C, Barth syndrome, histiocytoid cardiomyopathy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, autosomal recessive limb-girdle muscular dystrophy type 2F, myofibrillar myopathy 1, autosomal recessive limb-girdle muscular dystrophy type 2E, dilated cardiomyopathy 1J, hypertrophic cardiomyopathy 25, autosomal recessive limb-girdle muscular dystrophy type 2D, DK1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2M, early-onset myopathy with fatal cardiomyopathy, PGM1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2W, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, Emery-Dreifuss muscular dystrophy, familial isolated dilated cardiomyopathy, cardiomyopathy, dilated, 1LL, cardiomyopathy, dilated, 1MM, cardiomyopathy, dilated, 100, cardiomyopathy, dilated, 2I, cardiomyopathy, dilated, 2j, cardiomyopathy, dilated, 2K, cardiomyopathy, dilated, 2l, cardiomyopathy, dilated, 1QQ, cardiomyopathy, dilated, 2M, cardiomyopathy, dilated, 3C

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

214 retrieved; paginated sample, class counts are floors:

54 likely pathogenic, 52 pathogenic/likely pathogenic, 51 conflicting classifications of pathogenicity, 32 uncertain significance, 25 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069307	NM_004281.4(BAG3):c.811C>T (p.Gln271Ter)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
2447229	NM_004281.4(BAG3):c.764G>A (p.Trp255Ter)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
684816	NM_004281.4(BAG3):c.969_972del (p.Lys324fs)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66414	NM_001927.4(DES):c.5G>T (p.Ser2Ile)	DES	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4525812	NM_004100.5(EYA4):c.1014del (p.Asp340fs)	EYA4	Pathogenic	criteria provided, single submitter
1710093	NM_001458.5(FLNC):c.404G>A (p.Trp135Ter)	FLNC	Pathogenic	criteria provided, single submitter
1710094	NM_001458.5(FLNC):c.5142C>A (p.Tyr1714Ter)	FLNC	Pathogenic	criteria provided, single submitter
1710101	NM_001458.5(FLNC):c.2405del (p.Gly802fs)	FLNC	Pathogenic	criteria provided, single submitter
1710102	NM_001458.5(FLNC):c.3908dup (p.Tyr1303Ter)	FLNC	Pathogenic	criteria provided, single submitter
1710103	NM_001458.5(FLNC):c.3943C>T (p.Gln1315Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
2682366	NM_001458.5(FLNC):c.1880_1887del (p.Asp627fs)	FLNC	Pathogenic	criteria provided, single submitter
620373	NM_001458.5(FLNC):c.4021C>T (p.Arg1341Ter)	FLNC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620418	NM_001458.5(FLNC):c.4969C>T (p.Arg1657Ter)	FLNC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074155	NM_001458.5(FLNC):c.7750_7769dup (p.Lys2591fs)	FLNC-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710095	NM_001458.5(FLNC):c.5503C>T (p.Gln1835Ter)	FLNC-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710097	NM_001458.5(FLNC):c.6907C>T (p.Gln2303Ter)	FLNC-AS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1710098	NM_001458.5(FLNC):c.7316_7317del (p.Val2439fs)	FLNC-AS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1710099	NM_001458.5(FLNC):c.7581del (p.Ile2527fs)	FLNC-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
843365	NM_001458.5(FLNC):c.6190dup (p.Val2064fs)	FLNC-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3629832	NM_170707.4(LMNA):c.1158-1G>A	LMNA	Pathogenic	criteria provided, single submitter
36473	NM_170707.4(LMNA):c.1003C>T (p.Arg335Trp)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3902642	NM_170707.4(LMNA):c.1233del (p.Gly413fs)	LMNA	Pathogenic	criteria provided, single submitter
3907369	NM_170707.4(LMNA):c.184C>A (p.Arg62Ser)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4688860	NC_000001.10:g.(?156084501)(156109873_?)del	LMNA	Pathogenic	criteria provided, single submitter
48093	NM_170707.4(LMNA):c.949G>A (p.Glu317Lys)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
48096	NM_170707.4(LMNA):c.961C>T (p.Arg321Ter)	LMNA	Pathogenic	criteria provided, multiple submitters, no conflicts
520447	NM_170707.4(LMNA):c.1494G>A (p.Trp498Ter)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66915	NM_170707.4(LMNA):c.608A>T (p.Glu203Val)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
691647	NM_170707.4(LMNA):c.711_729delinsCC (p.Glu238fs)	LMNA	Pathogenic	criteria provided, multiple submitters, no conflicts
200956	NM_170707.4(LMNA):c.381_383delinsTGGTCACCTGAGAG (p.Ile128fs)	LOC126805877	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 138 · 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
LDB3	Strong	Autosomal recessive	cardiomyopathy, dilated, 2l	11
ANKRD1	Supportive	Autosomal dominant	familial isolated dilated cardiomyopathy	5
MYBPHL	Limited	Unknown	familial dilated cardiomyopathy

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
SCN5A	Orphanet:101016	Romano-Ward syndrome
SCN5A	Orphanet:130	Brugada syndrome
SCN5A	Orphanet:1344	Isolated atrial standstill
SCN5A	Orphanet:154	Familial isolated dilated cardiomyopathy
SCN5A	Orphanet:166282	Hereditary sick sinus syndrome
SCN5A	Orphanet:228140	Idiopathic ventricular fibrillation
SCN5A	Orphanet:334	Hereditary atrial fibrillation
SCN5A	Orphanet:871	Hereditary progressive cardiac conduction defect
SGCD	Orphanet:154	Familial isolated dilated cardiomyopathy
SGCD	Orphanet:219	Delta-sarcoglycan-related limb-girdle muscular dystrophy R6
TAFAZZIN	Orphanet:111	Barth syndrome
TAFAZZIN	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TNNT2	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNT2	Orphanet:54260	Left ventricular noncompaction
TNNT2	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
VCL	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTN2	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTN2	Orphanet:708129	Autosomal recessive ACTN2-related distal myopathy
ACTN2	Orphanet:708133	Autosomal dominant ACTN2-related distal myopathy
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
RBM20	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

40 cohort genes, 36 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	40

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	gencc,clinvar
ANKRD1	HGNC:15819	ENSG00000148677	Q15327	Ankyrin repeat domain-containing protein 1	gencc
MYBPHL	HGNC:30434	ENSG00000221986	A2RUH7	Myosin-binding protein H-like	gencc
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar
SGCD	HGNC:10807	ENSG00000170624	Q92629	Delta-sarcoglycan	clinvar
SRPK3	HGNC:11402	ENSG00000184343	Q9UPE1	SRSF protein kinase 3	clinvar
TAFAZZIN	HGNC:11577	ENSG00000102125	Q16635	Tafazzin	clinvar
TNNI3	HGNC:11947	ENSG00000129991	P19429	Troponin I, cardiac muscle	clinvar
TNNT2	HGNC:11949	ENSG00000118194	P45379	Troponin T, cardiac muscle	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
VCL	HGNC:12665	ENSG00000035403	P18206	Vinculin	clinvar
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	clinvar
MYPN	HGNC:23246	ENSG00000138347	Q86TC9	Myopalladin	clinvar
RBM20	HGNC:27424	ENSG00000203867	Q5T481	RNA-binding protein 20	clinvar
DES	HGNC:2770	ENSG00000175084	P17661	Desmin	clinvar
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	clinvar
NEXN	HGNC:29557	ENSG00000162614	Q0ZGT2	Nexilin	clinvar
MYLK3	HGNC:29826	ENSG00000140795	Q32MK0	Myosin light chain kinase 3	clinvar
DSC2	HGNC:3036	ENSG00000134755	Q02487	Desmocollin-2	clinvar
DSC3	HGNC:3037	ENSG00000134762	Q14574	Desmocollin-3	clinvar
DSG2	HGNC:3049	ENSG00000046604	Q14126	Desmoglein-2	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar
EMD	HGNC:3331	ENSG00000102119	P50402	Emerin	clinvar
EYA4	HGNC:3522	ENSG00000112319	O95677	Protein phosphatase EYA4	clinvar
FKTN	HGNC:3622	ENSG00000106692	O75072	Ribitol-5-phosphate transferase FKTN	clinvar
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	clinvar
TTN-AS1	HGNC:44124	ENSG00000237298		TTN antisense RNA 1	clinvar
P2RX5-TAX1BP3	HGNC:49191	ENSG00000257950		P2RX5-TAX1BP3 readthrough (NMD candidate)	clinvar
MHRT	HGNC:51291			myosin heavy chain associated RNA transcript	clinvar
FLNC-AS1	HGNC:53474	ENSG00000242902		FLNC antisense RNA 1	clinvar
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	clinvar
JUP	HGNC:6207	ENSG00000173801	P14923	Junction plakoglobin	clinvar
KCNH2	HGNC:6251	ENSG00000055118	Q12809	Voltage-gated inwardly rectifying potassium channel KCNH2	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	clinvar
ASPA	HGNC:756	ENSG00000108381	P45381	Aspartoacylase	clinvar
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
BAG3	HGNC:939	ENSG00000151929	O95817	BAG family molecular chaperone regulator 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
MYBPHL	Myosin-binding protein H-like	Myosin-binding protein which plays a role in cardiac function.
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.
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.
SGCD	Delta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
SRPK3	SRSF protein kinase 3	Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains.
TAFAZZIN	Tafazzin	Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary fo…
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.
TNNT2	Troponin T, cardiac 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.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
VCL	Vinculin	Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion.
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
MYPN	Myopalladin	Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.
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.
DES	Desmin	Muscle-specific type III intermediate filament essential for proper muscular structure and function.
DMD	Dystrophin	Anchors the extracellular matrix to the cytoskeleton via F-actin.
NEXN	Nexilin	Involved in regulating cell migration through association with the actin cytoskeleton.
MYLK3	Myosin light chain kinase 3	Kinase that phosphorylates MYL2 in vitro.
DSC2	Desmocollin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DSC3	Desmocollin-3	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DSG2	Desmoglein-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
EMD	Emerin	Stabilizes and promotes the formation of a nuclear actin cortical network.
EYA4	Protein phosphatase EYA4	Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair…
FKTN	Ribitol-5-phosphate transferase FKTN	Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydra…
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).
JUP	Junction plakoglobin	Common junctional plaque protein.
KCNH2	Voltage-gated inwardly rectifying potassium channel KCNH2	Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.
LMNA	Prelamin-A/C	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
MYBPC3	Myosin-binding protein C, cardiac-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.
ASPA	Aspartoacylase	Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate.
MYH6	Myosin-6	Muscle contraction.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
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.

Protein-family classification

Druggable: 13 · Difficult: 8 · Unknown: 19 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	3	8.4×	0.044
Antibody/Immunoglobulin	5	3.6×	0.045
Scaffold/PPI	5	2.2×	0.211
Kinase	3	2.1×	0.348
Transporter	1	1.9×	0.647
Other/Unknown	19	0.8×	0.969
Transcription factor	3	0.6×	0.969
Enzyme (other)	1	0.3×	0.969

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
ANKRD1	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
MYBPHL	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
SGCD	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
SRPK3	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TAFAZZIN	Other/Unknown	no		Tafazzin, Plipid/glycerol_acylTrfase
TNNI3	Other/Unknown	no		Troponin, Troponin-I_N, Troponin_sf
TNNT2	Other/Unknown	no		Troponin, TNNT, Troponin_sf
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
VCL	Other/Unknown	no		Vinculin_CS, Vinculin/catenin, Vinculin
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
MYPN	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
RBM20	Transcription factor	no		RRM_dom, Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2
DES	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
NEXN	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_I-set
MYLK3	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DSC2	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin
DSC3	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin
DSG2	Other/Unknown	no		Cadherin-like_dom, Desmosomal_cadherin, Cadherin-like_sf
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
EMD	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, LEM_emerin
EYA4	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
FKTN	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
TTN-AS1	Other/Unknown	no
P2RX5-TAX1BP3	Other/Unknown	no
MHRT	Other/Unknown	no
FLNC-AS1	Other/Unknown	no
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
JUP	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
KCNH2	Ion channel	yes		PAS, cNMP-bd_dom, PAS-assoc_C
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
ASPA	Enzyme (other)	yes	3.5.1.15	Aste_AspA_hybrid_dom, Aspartoacylase, AspA/AstE_fam
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYH7	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
BAG3	Scaffold/PPI	no		WW_dom, BAG_domain, WW_dom_sf

Expression context

Cohort genes with no expression data: 1.

34 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)	39
unknown	1

Top tissues across cohort

Tissue	Cohort genes
apex of heart	11
hindlimb stylopod muscle	9
right atrium auricular region	7
gastrocnemius	7
skeletal muscle tissue of biceps brachii	5
cardiac atrium	5
left ventricle myocardium	5
skeletal muscle tissue of rectus abdominis	5
myocardium	4
heart right ventricle	3
cardiac muscle of right atrium	3
male germ line stem cell (sensu Vertebrata) in testis	2
gluteal muscle	2
lower esophagus mucosa	2
biceps brachii	2
saphenous vein	2
gingiva	2
gingival epithelium	2
upper leg skin	2
muscle of leg	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
MYBPHL	123	tissue_specific	yes	right atrium auricular region, male germ line stem cell (sensu Vertebrata) in testis, Ammon’s horn
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
SGCD	247	broad	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, heart right ventricle
SRPK3	202	broad	marker	hindlimb stylopod muscle, gluteal muscle, gastrocnemius
TAFAZZIN	238	ubiquitous	marker	apex of heart, granulocyte, lower esophagus mucosa
TNNI3	169	broad	marker	apex of heart, left ventricle myocardium, right atrium auricular region
TNNT2	154	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
VCL	300	ubiquitous	marker	saphenous vein, blood vessel layer, urethra
ACTN2	226	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle
MYPN	116	broad	marker	hindlimb stylopod muscle, gastrocnemius, vastus lateralis
RBM20	191	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
DES	280	broad	marker	apex of heart, saphenous vein, gastrocnemius
DMD	295	ubiquitous	marker	trigeminal ganglion, skeletal muscle tissue of rectus abdominis, dorsal root ganglion
NEXN	229	ubiquitous	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, myocardium
MYLK3	194	tissue_specific	marker	cardiac muscle of right atrium, myocardium, heart right ventricle
DSC2	256	ubiquitous	marker	gingival epithelium, gingiva, oral cavity
DSC3	177	broad	marker	upper leg skin, gingival epithelium, gingiva
DSG2	238	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, jejunal mucosa
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
EMD	284	ubiquitous	marker	left ovary, left uterine tube, popliteal artery
EYA4	208	broad	marker	biceps brachii, skeletal muscle tissue of biceps brachii, seminal vesicle
FKTN	277	ubiquitous	yes	calcaneal tendon, adrenal tissue, germinal epithelium of ovary
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
TTN-AS1	174	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, right atrium auricular region
P2RX5-TAX1BP3	126	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, spleen, cortical plate
MHRT

Protein interactions among cohort

Intra-cohort edges: 91.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
BAG3	4,957
JUP	4,618
VCL	4,495
TTN	4,237
EMD	3,503
FLNC	3,174
MYH6	3,119
DSP	2,897
ACTN2	2,781

Intra-cohort edges

A	B	Sources
ABCC9	ACTN2	string_interaction
ABCC9	DSG2	string_interaction
ABCC9	EYA4	string_interaction
ABCC9	LDB3	string_interaction
ABCC9	MYBPC3	string_interaction
ABCC9	NEXN	string_interaction
ABCC9	RBM20	string_interaction
ABCC9	SCN5A	string_interaction
ABCC9	SGCD	string_interaction
ACTN2	LDB3	biogrid_interaction, intact, string_interaction
ACTN2	MYH6	biogrid_interaction, string_interaction
ACTN2	MYH7	biogrid_interaction, string_interaction
ACTN2	MYPN	biogrid_interaction, string_interaction
ACTN2	NEXN	string_interaction
ACTN2	TNNT2	string_interaction
ACTN2	TTN	string_interaction
ACTN2	VCL	string_interaction
ANKRD1	MYPN	biogrid_interaction, string_interaction
ANKRD1	TTN	biogrid_interaction, string_interaction
BAG3	EYA4	biogrid_interaction
BAG3	FLNC	string_interaction
BAG3	LDB3	string_interaction
DES	DMD	string_interaction
DES	DSP	string_interaction
DMD	FLNC	string_interaction
DMD	SGCD	string_interaction
DMD	TAFAZZIN	string_interaction
DMD	VCL	string_interaction
DSC2	DSG2	intact, string_interaction
DSC2	DSP	string_interaction
DSC2	JUP	biogrid_interaction, string_interaction
DSC2	LMNA	string_interaction
DSC2	RYR2	string_interaction
DSC3	DSG2	intact, string_interaction
DSC3	DSP	string_interaction
DSC3	JUP	biogrid_interaction, string_interaction
DSC3	RYR2	string_interaction
DSG2	DSP	string_interaction
DSG2	EYA4	string_interaction
DSG2	JUP	intact, string_interaction
DSG2	MYBPC3	string_interaction
DSG2	RBM20	string_interaction
DSG2	RYR2	string_interaction
DSG2	SCN5A	string_interaction
DSP	JUP	intact, string_interaction
EMD	LMNA	intact, string_interaction
EYA4	FKTN	string_interaction
EYA4	MYBPC3	string_interaction
EYA4	NEXN	string_interaction
EYA4	RBM20	string_interaction

Structural data

PDB: 20 · AlphaFold-only: 16 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
MYH7	P12883	43
TNNI3	P19429	39
VCL	P18206	37
LMNA	P02545	28
RYR2	Q92736	26
TNNT2	P45379	25
KCNH2	Q12809	24
MYBPC3	Q14896	17
SCN5A	Q14524	16
ACTN2	P35609	16
FLNC	Q14315	14
DSG2	Q14126	12
ASPA	P45381	8
DMD	P11532	6
EMD	P50402	6
DSP	P15924	4
DSC2	Q02487	3
LDB3	O75112	2
JUP	P14923	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TAFAZZIN	Q16635	94.87
FKTN	O75072	92.48
MYBPHL	A2RUH7	86.64
ANKRD1	Q15327	82.64
ABCC9	O60706	81.72
SGCD	Q92629	81.43
SRPK3	Q9UPE1	80.61
DES	P17661	77.73
DSC3	Q14574	75.53
MYH6	P13533	74.91
NEXN	Q0ZGT2	70.78
EYA4	O95677	63.79
MYLK3	Q32MK0	63.26
BAG3	O95817	57.98
MYPN	Q86TC9	52.71
RBM20	Q5T481	48.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 40 evidence-associated genes (28 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 28 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	8	88.2×	2e-12	TNNI3, TNNT2, TTN, ACTN2, DES, DMD, MYBPC3, MYH6
Muscle contraction	7	19.3×	3e-06	RYR2, SCN5A, ACTN2, ABCC9, KCNH2, MYBPC3, MYH6
Formation of the cornified envelope	5	15.7×	5e-04	DSC2, DSC3, DSG2, DSP, JUP
Cardiac conduction	4	15.5×	0.003	RYR2, SCN5A, ABCC9, KCNH2
Keratinization	5	9.9×	0.003	DSC2, DSC3, DSG2, DSP, JUP
Apoptotic cleavage of cell adhesion proteins	2	74.2×	0.005	DSG2, DSP
Regulation of CDH1 Function	2	68.0×	0.005	VCL, JUP
Ion homeostasis	3	21.9×	0.005	RYR2, TNNI3, ABCC9
Depolymerization of the Nuclear Lamina	2	54.4×	0.008	EMD, LMNA
Initiation of Nuclear Envelope (NE) Reformation	2	42.9×	0.011	EMD, LMNA
Nuclear Envelope Breakdown	2	32.6×	0.018	EMD, LMNA
Formation of the dystrophin-glycoprotein complex (DGC)	2	22.1×	0.034	SGCD, DMD
Platelet degranulation	3	9.4×	0.034	TTN, VCL, ACTN2
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	203.9×	0.041	ABCC9
Breakdown of the nuclear lamina	1	135.9×	0.057	LMNA
ATP sensitive Potassium channels	1	102.0×	0.071	ABCC9
Signaling by BRAF and RAF1 fusions	2	12.2×	0.079	VCL, LMNA
Activation of STAT3 by cadherin engagement	2	11.7×	0.081	VCL, JUP
Acyl chain remodeling of CL	1	68.0×	0.084	TAFAZZIN
Non-integrin membrane-ECM interactions	2	11.0×	0.084	SGCD, DMD
RHOG GTPase cycle	2	10.6×	0.084	DSG2, EMD
CDH11 homotypic and heterotypic interactions	1	58.3×	0.090	JUP
Potassium Channels	2	9.6×	0.092	ABCC9, KCNH2
Regulation of CDH19 Expression and Function	1	51.0×	0.094	JUP
RAC2 GTPase cycle	2	9.1×	0.094	DSG2, EMD
Phase 3 - rapid repolarisation	1	40.8×	0.102	KCNH2
RAC3 GTPase cycle	2	8.5×	0.102	DSG2, EMD
Neuronal System	3	4.7×	0.102	ACTN2, ABCC9, KCNH2
Aspartate and asparagine metabolism	1	37.1×	0.103	ASPA
Regulation of CDH11 function	1	37.1×	0.103	JUP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 36 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	10	111.5×	2e-16	RYR2, SCN5A, TNNI3, TNNT2, TTN, DMD, KCNH2, MYBPC3 (+2 more)
sarcomere organization	10	106.4×	2e-16	LDB3, TNNT2, TTN, ANKRD1, ACTN2, MYPN, MYLK3, FLNC (+2 more)
regulation of ventricular cardiac muscle cell action potential	5	195.1×	3e-09	RYR2, DSC2, DSG2, DSP, JUP
muscle filament sliding	5	146.3×	1e-08	TNNI3, TNNT2, TTN, MYH6, MYH7
regulation of heart rate by cardiac conduction	6	62.4×	3e-08	SCN5A, DSC2, DSG2, DSP, JUP, KCNH2
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	4	267.5×	4e-08	DSC2, DSG2, DSP, JUP
ventricular cardiac muscle tissue morphogenesis	5	97.5×	7e-08	TNNI3, TNNT2, MYBPC3, MYH6, MYH7
regulation of heart rate	5	65.0×	5e-07	RYR2, SCN5A, DMD, MYH6, MYH7
striated muscle contraction	4	93.6×	3e-06	RYR2, TTN, MYH6, MYH7
cardiac muscle cell development	4	69.3×	1e-05	SGCD, TTN, ACTN2, MYH6
muscle contraction	5	28.9×	2e-05	TTN, DES, EMD, MYH6, MYH7
muscle organ development	5	23.2×	7e-05	SGCD, DMD, EMD, FKTN, LMNA
homophilic cell-cell adhesion	5	19.5×	1e-04	MYPN, NEXN, DSC2, DSC3, DSG2
ventricular cardiac muscle cell action potential	3	82.6×	1e-04	RYR2, SCN5A, KCNH2
sarcomerogenesis	2	312.1×	3e-04	TTN, MYLK3
response to muscle stretch	3	63.8×	3e-04	RYR2, ANKRD1, DMD
cell-cell adhesion	5	14.1×	5e-04	DSC2, DSC3, DSG2, DSP, JUP
skeletal muscle contraction	3	42.6×	9e-04	TNNI3, TTN, MYH7
regulation of heart contraction	3	41.3×	9e-04	TNNT2, DES, MYH6
ATP metabolic process	3	39.0×	0.001	ABCC9, MYH6, MYH7
desmosome organization	2	117.0×	0.002	DSG2, DSP
cardiac muscle hypertrophy	2	93.6×	0.003	RYR2, TTN
negative regulation of ATP-dependent activity	2	93.6×	0.003	TNNI3, TNNT2
cardiac muscle cell contraction	2	93.6×	0.003	SGCD, ABCC9
membrane depolarization during action potential	2	93.6×	0.003	SCN5A, KCNH2
skeletal muscle tissue development	3	24.2×	0.003	SRPK3, DMD, ABCC9
cardiac muscle tissue morphogenesis	2	78.0×	0.004	TTN, ANKRD1
regulation of cardiac muscle contraction by calcium ion signaling	2	72.0×	0.004	RYR2, TNNI3
cardiac myofibril assembly	2	72.0×	0.004	TTN, MYLK3
cell adhesion	6	6.2×	0.004	VCL, ACTN2, DSC2, DSC3, DSG2, MYBPC3

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 33

Druggability breadth: 19 of 40 evidence-associated genes (48%) 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
SCN5A	BEPRIDIL
SRPK3	FEDRATINIB
MYLK3	FEDRATINIB
ABCC9	PINACIDIL ANHYDROUS
KCNH2	CETIRIZINE
LMNA	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
KCNH2	706	4
SCN5A	108	4
MYLK3	24	4
SRPK3	18	4
ABCC9	5	4
RYR2	1	2
LDB3	0	0
ANKRD1	0	0
MYBPHL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	KCNH2, LMNA, SCN5A
IMIPRAMINE	4	KCNH2, LMNA, SCN5A
DROPERIDOL	4	KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	KCNH2, SCN5A
PALONOSETRON	4	KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNH2, SCN5A
FEDRATINIB	4	KCNH2, MYLK3, SCN5A, SRPK3
QUINIDINE	4	KCNH2, SCN5A
DARUNAVIR	4	KCNH2, SCN5A
DARIFENACIN	4	KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNH2, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	KCNH2, LMNA, SCN5A
NIMODIPINE	4	LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	KCNH2, LMNA, SCN5A
AMLODIPINE	4	KCNH2, SCN5A
PHENYTOIN	4	KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
KCNH2	4,851	Binding:3558, Toxicity:1071, Functional:169, ADMET:53
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
SRPK3	229	Binding:229
MYLK3	95	Binding:95
ABCC9	61	Functional:46, Binding:15
RYR2	15	Binding:15
LMNA	12	Binding:9, Functional:3
BAG3	8	Binding:8
TNNI3	2	Binding:2
TNNT2	2	Binding:2
VCL	2	Binding:2
DSP	2	Binding:2
TAFAZZIN	1	Binding:1
TTN	1	Binding:1
EMD	1	Binding:1
JUP	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRPK3	2.7.11.1	non-specific serine/threonine protein kinase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
ASPA	3.5.1.15	aspartoacylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN5A	594
SRPK3	229
KCNH2	4,851

Pharmacogenomics

Cohort genes with a PharmGKB record: 36; 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)
BEPRIDIL	4	KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	KCNH2, LMNA, SCN5A
IMIPRAMINE	4	KCNH2, LMNA, SCN5A
DROPERIDOL	4	KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	KCNH2, SCN5A
PALONOSETRON	4	KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNH2, SCN5A
FEDRATINIB	4	KCNH2, MYLK3, SCN5A, SRPK3
QUINIDINE	4	KCNH2, SCN5A
DARUNAVIR	4	KCNH2, SCN5A
DARIFENACIN	4	KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNH2, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	KCNH2, LMNA, SCN5A
NIMODIPINE	4	LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	KCNH2, LMNA, SCN5A
AMLODIPINE	4	KCNH2, SCN5A
PHENYTOIN	4	KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	SCN5A, SRPK3, MYLK3, ABCC9, KCNH2, LMNA
B	Phased (≥1) drug, not yet approved	1	RYR2
C	Druggable family + PDB, no drug	4	TTN, FLNC, MYBPC3, ASPA
D	Druggable family + AlphaFold only, no drug	3	MYBPHL, MYPN, NEXN
E	Difficult family or no structure, no drug	26	LDB3, ANKRD1, SGCD, TAFAZZIN, TNNI3, TNNT2, VCL, ACTN2, RBM20, DES (+16 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RBM20	0	ABCC9
EMD	1	LMNA
EYA4	0	ABCC9
LDB3	0	—
ANKRD1	0	—
MYBPHL	0	—
SGCD	0	—
TAFAZZIN	1	—
TNNI3	2	—
TNNT2	2	—
TTN	1	—
VCL	2	—
ACTN2	0	—
MYPN	0	—
DES	0	—
DMD	0	—
NEXN	0	—
DSC2	0	—
DSC3	0	—
DSG2	0	—
DSP	2	—
FKTN	0	—
FLNC	0	—
TTN-AS1	0	—
P2RX5-TAX1BP3	0	—
MHRT	0	—
FLNC-AS1	0	—
JUP	1	—
MYBPC3	0	—
ASPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	1
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01798992	PHASE4	COMPLETED	Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
NCT02987322	PHASE2/PHASE3	COMPLETED	Honey in Idiopathic Dilated Cardiomyopathy
NCT02033278	PHASE2	TERMINATED	Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
NCT03037632	Not specified	ACTIVE_NOT_RECRUITING	DCM Precision Medicine Study
NCT03049254	Not specified	RECRUITING	Mayo AVC Registry and Biobank
NCT06356727	Not specified	RECRUITING	Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling
NCT07420907	Not specified	RECRUITING	Study of the Progression of Chronic Cardiovascular Conditions
NCT03860454	Not specified	UNKNOWN	The Deep Phenotype of Lamin A/C Cardiomyopathy
NCT05769387	Not specified	COMPLETED	Multihormonal Deficiencies and miRNA Profile in Chronic Heart Failure: Effects of Combined Hormonal Replacement Therapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOXAZOSIN	4	3
CARVEDILOL	4	1
METOPROLOL SUCCINATE	4	1
HONEY	3	1
(R)-Carvedilol	0	1