Heart disorder

Summary

Heart disorder (MONDO:0005267) is a disease (an umbrella term covering 34 Mondo subtypes) with 4 cohort genes (232 GWAS associations across 139 studies) and 1,751 clinical trials. The dominant Reactome pathway is Muscle contraction (3 cohort genes). Top therapeutic interventions include imipramine, metoprolol, and amiodarone.

At a glance

• Umbrella term: 34 Mondo subtypes
• Cohort genes: 4
• GWAS associations: 232
• ClinVar variants: 4
• Clinical trials: 1,751

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heart disorder
Mondo ID	MONDO:0005267
EFO	EFO:0003777
MeSH	D006331
DOID	DOID:114
ICD-11	1512587470
NCIT	C3079
SNOMED CT	56265001
UMLS	C0018799
MedGen	5458
Anatomy (UBERON)	UBERON:0015410
Is cancer (heuristic)	no

Also known as: cardiac disease · disease of heart · disease or disorder of heart · disorder of heart · disorder of heart/pericardium · heart disease · heart disease or disorder · heart disorder · heart trouble · heart/pericardial disease · heart/pericardial disease or disorder · heart/pericardial disorder · heart/pericardial trouble

Data availability: 4 ClinVar variants · 232 GWAS associations (139 studies) · 17 cell lines.

Disease family

An umbrella term covering 34 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder

Related subtypes (5): autoimmune disorder of cardiovascular system, vascular disorder, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, congenital anomaly of cardiovascular system, cardiovascular neoplasm

Subtypes (34): endocardium disorder, pericardium disorder, cardiac tuberculosis, heart conduction disease, hypertensive heart disease, heart valve disorder, cardiomyopathy, coronary artery disorder, heart failure, congenital heart disease, heart aneurysm, rheumatic heart disease, cardiac rhythm disease, white forelock with malformations, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, PHACE syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, cardiac anomalies-heterotaxy syndrome, polyvalvular heart disease syndrome, Thomas syndrome, 22q11.2 deletion syndrome, myocardial rupture, heart neoplasm, aortopulmonary window, cor biloculare, inflammation of heart layer, myocardial disorder, carcinoid heart disease, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, coronary microvascular disorder, cardiac ventricle disorder, cardiogenetic disease, cardiogenic shock

Genetics & variants

GWAS landscape

232 GWAS associations across 139 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr9:22093299	2e-235		A	0.18
rs10455872	3e-165	LPA	A	0.28
rs1537373	7e-143	CDKN2B-AS1	T	0.17
rs1894692	2e-105	SLC19A2 - F5	G	0.76
chr4:110791530	8e-102		C	0.15
rs115478735	4e-85	ABO	A	0.31
rs9349379	5e-73	PHACTR1	A	0.1
rs583104	3e-69	CELSR2 - PSRC1	G	0.12
rs3756011	6e-68	F11	C	0.23
rs4444878	2e-64	F11-AS1	C	0.24
rs1799963	7e-59	F2	G	0.69
rs2066865	7e-59	FGA - FGG	G	0.22
rs7528419	7e-46	CELSR2	A	0.11
rs9980618	2e-45	KCNE2, MRPS6, LINC00310	C	0.11
rs2066864	5e-45	FGG	G	0.14
rs4253417	4e-43	F11	T	0.13
rs9515203	7e-42	COL4A2	T	0.08
chr10:44742572	4e-40		G	0.12
chr1:222811407	2e-33		A	0.07
rs964184	2e-30	ZPR1	G	0.09
chr19:11190544	2e-30		C	0.09
rs10176176	2e-29	PARTICL	A	0.06
chr2:203839628	5e-29		T	0.09
rs494207	2e-28	LINC00841 - LINC03089	G	0.1
rs78707713	3e-27	TSPAN15	T	0.25
rs28451064	3e-27	KCNE2, MRPS6, LINC00310	G	0.12
rs12190287	4e-27	TCF21, TARID	C	0.06
rs429358	1e-26	APOE	T	0.08
rs17490626	3e-26	TSPAN15	G	0.24
chr1:154873058	1e-25		C	0.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90042664	Jiang L	2021	131,326	270,663	A generalized linear mixed model association tool for biobank-scale data.
GCST90042677	Jiang L	2021	84,417	335,864	A generalized linear mixed model association tool for biobank-scale data.
GCST90473552	UK Biobank Whole-Genome Sequencing Consortium	2025	83,174	375,266	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90475938	Verma A	2024	71,808	357,986	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90042690	Jiang L	2021	37,330	320,951	A generalized linear mixed model association tool for biobank-scale data.
GCST90038605	Donertas HM	2021	34,616	449,982	Common genetic associations between age-related diseases.
GCST90079982	Backman JD	2021	32,706	354,404	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083968	Backman JD	2021	32,706	354,404	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90473578	UK Biobank Whole-Genome Sequencing Consortium	2025	23,301	435,139	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90475942	Verma A	2024	23,279	414,175	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	2
Tier 2: splice/UTR	6
Tier 3: regulatory	1
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	19
unknown	14
3_prime_UTR_variant	6
intergenic_variant	4
non_coding_transcript_exon_variant	3
missense_variant	2
regulatory_region_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr9:22093299				0.487			2e-235	Tier 4: intronic/intergenic
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	3e-165	Tier 4: intronic/intergenic
rs1537373	9	22103342	T>A,G	0.421	intron_variant	CDKN2B-AS1	7e-143	Tier 4: intronic/intergenic
rs1894692	1	169498416	G>A	0.036	non_coding_transcript_exon_variant	SLC19A2 - F5	2e-105	Tier 4: intronic/intergenic
chr4:110791530							8e-102	Tier 4: intronic/intergenic
rs115478735	9	133274295	A>T	0.158	intron_variant	ABO	4e-85	Tier 4: intronic/intergenic
rs9349379	6	12903725	A>C,G,T	0.402	intron_variant	PHACTR1	5e-73	Tier 4: intronic/intergenic
rs583104	1	109278685	G>A,C,T	0.229	intergenic_variant	CELSR2 - PSRC1	3e-69	Tier 4: intronic/intergenic
rs3756011	4	186285095	C>A,T	0.364	intron_variant	F11	6e-68	Tier 4: intronic/intergenic
rs4444878	4	186292729	C>A,G,T	0.393	intron_variant	F11-AS1	2e-64	Tier 4: intronic/intergenic
rs1799963	11	46739505	G>A	0.012	3_prime_UTR_variant	F2	7e-59	Tier 2: splice/UTR
rs2066865	4	154604124	G>A,C,T	0.25	intergenic_variant	FGA - FGG	7e-59	Tier 4: intronic/intergenic
rs7528419	1	109274570	A>G	0.225	3_prime_UTR_variant	CELSR2	7e-46	Tier 2: splice/UTR
rs9980618	21	34228204	C>T	0.131	intron_variant	KCNE2, MRPS6, LINC00310	2e-45	Tier 4: intronic/intergenic
rs2066864	4	154604543	G>A,T	0.25	3_prime_UTR_variant	FGG	5e-45	Tier 2: splice/UTR
rs4253417	4	186277851	T>C,G	0.345	intron_variant	F11	4e-43	Tier 4: intronic/intergenic
rs9515203	13	110397276	T>C	0.262	intron_variant	COL4A2	7e-42	Tier 4: intronic/intergenic
chr10:44742572				0.104			4e-40	Tier 4: intronic/intergenic
chr1:222811407				0.285			2e-33	Tier 4: intronic/intergenic
rs964184	11	116778201	G>C	0.14	3_prime_UTR_variant	ZPR1	2e-30	Tier 2: splice/UTR
chr19:11190544				0.119			2e-30	Tier 4: intronic/intergenic
rs10176176	2	85534925	A>C,T	0.481	non_coding_transcript_exon_variant	PARTICL	2e-29	Tier 4: intronic/intergenic
chr2:203839628				0.127			5e-29	Tier 4: intronic/intergenic
rs494207	10	44245808	G>A	0.178	regulatory_region_variant	LINC00841 - LINC03089	2e-28	Tier 3: regulatory
rs78707713	10	69485520	T>A,C	0.121	intron_variant	TSPAN15	3e-27	Tier 4: intronic/intergenic
rs28451064	21	34221526	G>A,T	0.098	intron_variant	KCNE2, MRPS6, LINC00310	3e-27	Tier 4: intronic/intergenic
rs12190287	6	133893387	C>A,G,T	0.37	3_prime_UTR_variant	TCF21, TARID	4e-27	Tier 2: splice/UTR
rs429358	19	44908684	T>C	0.14	missense_variant	APOE	1e-26	Tier 1: coding
rs17490626	10	69458890	G>A,C	0.099	intron_variant	TSPAN15	3e-26	Tier 4: intronic/intergenic
chr1:154873058							1e-25	Tier 4: intronic/intergenic

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
374032	NM_000138.5(FBN1):c.5180G>A (p.Arg1727Gln)	FBN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191718	NM_002471.4(MYH6):c.2575G>T (p.Gly859Trp)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222789	NM_001035.3(RYR2):c.6022+5G>A	RYR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374033	NM_002234.4(KCNA5):c.1703G>T (p.Gly568Val)	KCNA5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
KCNA5	Orphanet:334	Hereditary atrial fibrillation
MYH6	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH6	Orphanet:166282	Hereditary sick sinus syndrome
MYH6	Orphanet:99103	Atrial septal defect, ostium secundum type

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
KCNA5	HGNC:6224	ENSG00000130037	P22460	Potassium voltage-gated channel subfamily A member 5	clinvar
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
KCNA5	Potassium voltage-gated channel subfamily A member 5	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
MYH6	Myosin-6	Muscle contraction.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

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	2	55.8×	0.001
Scaffold/PPI	1	4.3×	0.318
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
KCNA5	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac atrium	2
cardiac muscle of right atrium	2
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
decidua	1
skin of hip	1
synovial joint	1
blood vessel layer	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
KCNA5	179	broad	marker	cardiac muscle of right atrium, blood vessel layer, cardiac atrium
MYH6	154	tissue_specific	yes	cardiac muscle of right atrium, cardiac atrium, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640
MYH6	3,119
RYR2	2,653
KCNA5	2,288

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RYR2	Q92736	26
FBN1	P35555	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH6	P13533	74.91
KCNA5	P22460	72.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Muscle contraction	3	57.9×	2e-04	RYR2, KCNA5, MYH6
Cardiac conduction	2	54.4×	0.004	RYR2, KCNA5
Phase 3 - rapid repolarisation	1	285.5×	0.021	KCNA5
Elastic fibre formation	1	84.0×	0.033	FBN1
TGF-beta receptor signaling activates SMADs	1	81.6×	0.033	FBN1
Molecules associated with elastic fibres	1	77.2×	0.033	FBN1
Striated Muscle Contraction	1	77.2×	0.033	MYH6
Voltage gated Potassium channels	1	60.7×	0.037	KCNA5
Ion homeostasis	1	51.0×	0.039	RYR2
Stimuli-sensing channels	1	34.0×	0.044	RYR2
Potassium Channels	1	33.6×	0.044	KCNA5
Integrin cell surface interactions	1	33.6×	0.044	FBN1
Degradation of the extracellular matrix	1	29.4×	0.046	FBN1
Post-translational protein phosphorylation	1	25.0×	0.049	FBN1
Ion channel transport	1	24.0×	0.049	RYR2
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	21.6×	0.051	FBN1
Neuronal System	1	11.1×	0.093	KCNA5
Transport of small molecules	1	6.3×	0.150	RYR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
striated muscle contraction	2	421.3×	8e-04	RYR2, MYH6
regulation of heart rate	2	234.1×	0.001	RYR2, MYH6
cardiac muscle contraction	2	200.6×	0.001	RYR2, MYH6
visceral muscle development	1	4213.0×	0.004	MYH6
establishment of protein localization to endoplasmic reticulum	1	4213.0×	0.004	RYR2
regulation of heart growth	1	2106.5×	0.005	MYH6
Purkinje myocyte to ventricular cardiac muscle cell signaling	1	2106.5×	0.005	RYR2
membrane repolarization during bundle of His cell action potential	1	2106.5×	0.005	KCNA5
membrane repolarization during SA node cell action potential	1	2106.5×	0.005	KCNA5
post-embryonic eye morphogenesis	1	1404.3×	0.005	FBN1
type B pancreatic cell apoptotic process	1	1404.3×	0.005	RYR2
regulation of AV node cell action potential	1	1404.3×	0.005	RYR2
regulation of atrial cardiac muscle cell action potential	1	1404.3×	0.005	RYR2
response to hypoxia	2	47.9×	0.005	RYR2, KCNA5
left ventricular cardiac muscle tissue morphogenesis	1	1053.2×	0.005	RYR2
obsolete sequestering of BMP in extracellular matrix	1	1053.2×	0.005	FBN1
obsolete sequestering of TGFbeta in extracellular matrix	1	1053.2×	0.005	FBN1
obsolete positive regulation of sequestering of calcium ion	1	1053.2×	0.005	RYR2
sarcoplasmic reticulum calcium ion transport	1	842.6×	0.005	RYR2
positive regulation of the force of heart contraction	1	842.6×	0.005	RYR2
negative regulation of osteoclast development	1	842.6×	0.005	FBN1
regulation of SA node cell action potential	1	702.2×	0.006	RYR2
membrane repolarization during atrial cardiac muscle cell action potential	1	702.2×	0.006	KCNA5
response to caffeine	1	601.9×	0.006	RYR2
atrial cardiac muscle tissue morphogenesis	1	601.9×	0.006	MYH6
regulation of atrial cardiac muscle cell membrane repolarization	1	601.9×	0.006	KCNA5
embryonic heart tube morphogenesis	1	468.1×	0.007	RYR2
membrane hyperpolarization	1	468.1×	0.007	KCNA5
cardiac muscle hypertrophy	1	421.3×	0.007	RYR2
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	421.3×	0.007	RYR2

Therapeutics

Drugs indicated for this disease

0 approved, 49 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Allopurinol	Phase 3 (in late-stage trials)
Amiodarone	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atenolol	Phase 3 (in late-stage trials)
Azithromycin	Phase 3 (in late-stage trials)
Bivalirudin	Phase 3 (in late-stage trials)
Candesartan	Phase 3 (in late-stage trials)
Chlorothiazide	Phase 3 (in late-stage trials)
Chlorthalidone	Phase 3 (in late-stage trials)
Cholestyramine	Phase 3 (in late-stage trials)
Clarithromycin	Phase 3 (in late-stage trials)
Clofibrate	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Dipyridamole	Phase 3 (in late-stage trials)
Edoxaban	Phase 3 (in late-stage trials)
Estradiol	Phase 3 (in late-stage trials)
Estrogen	Phase 3 (in late-stage trials)
Estrogens, Conjugated	Phase 3 (in late-stage trials)
Fibrinogen, Human	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Heparin	Phase 3 (in late-stage trials)
Lovastatin	Phase 3 (in late-stage trials)
Medroxyprogesterone Acetate	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Moxonidine	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Niacin	Phase 3 (in late-stage trials)
Nitroglycerin	Phase 3 (in late-stage trials)
Norepinephrine	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Potassium Chloride	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Propranolol	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Rauwolfia Serpentina	Phase 3 (in late-stage trials)
Remifentanil	Phase 3 (in late-stage trials)
Reserpine	Phase 3 (in late-stage trials)
Sivelestat	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sotalol	Phase 3 (in late-stage trials)
Streptokinase	Phase 3 (in late-stage trials)
Sulfur Hexafluoride	Phase 3 (in late-stage trials)
Tacrolimus Anhydrous	Phase 3 (in late-stage trials)
Telmisartan	Phase 3 (in late-stage trials)
Udenafil	Phase 3 (in late-stage trials)
Vasopressin	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acebutolol, Amlodipine, Anti-Inhibitor Coagulant Complex, Ascorbic Acid, Beta Carotene, Calcium, Captopril, Clopidogrel, Colchicine, Cyanocobalamin, Doxazosin, Enalapril, Fosinopril, Hydralazine, Ketorolac, Levosimendan, Lidocaine, Metoprolol, Pentoxifylline, Prasugrel, Pyridoxine, Rivaroxaban, Sodium Bicarbonate, Sodium Dichloroacetate, Vitamin E.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
KCNA5	DRONEDARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNA5	8	4
RYR2	1	2
FBN1	0	0
MYH6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DRONEDARONE HYDROCHLORIDE	4	KCNA5
SERTINDOLE	4	KCNA5
QUINIDINE	4	KCNA5
NIFEDIPINE	4	KCNA5
VERNAKALANT HYDROCHLORIDE	4	KCNA5
FLECAINIDE	4	KCNA5
ALADORIAN	2	RYR2
BMS-919373	2	KCNA5
BMS-394136	1	KCNA5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNA5	152	Binding:130, Functional:14, ADMET:5, Toxicity:3
RYR2	15	Binding:15

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KCNA5	152

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

8 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)
DRONEDARONE HYDROCHLORIDE	4	KCNA5
SERTINDOLE	4	KCNA5
NIFEDIPINE	4	KCNA5
VERNAKALANT HYDROCHLORIDE	4	KCNA5
FLECAINIDE	4	KCNA5
ALADORIAN	2	RYR2
BMS-919373	2	KCNA5
BMS-394136	1	KCNA5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNA5
B	Phased (≥1) drug, not yet approved	1	RYR2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	FBN1, MYH6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FBN1	0	—
MYH6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,751.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	760
PHASE3	171
PHASE2	77
PHASE4	51
PHASE1	21
PHASE2/PHASE3	10
PHASE1/PHASE2	8
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02817360	PHASE4	RECRUITING	NT-proBNP Selected Prevention of Cardiac Events in Diabetic Patients
NCT04522622	PHASE4	RECRUITING	Treatment of Adynamic Bone Disorder With Parathyroid Hormone in Chronic Kidney Disease
NCT05019027	PHASE4	ENROLLING_BY_INVITATION	N-of-1 for Beta-Blockers in Cardiac Amyloidosis
NCT05498376	PHASE4	ACTIVE_NOT_RECRUITING	The Leadless AV Versus DDD Pacing Study
NCT05585125	PHASE4	ENROLLING_BY_INVITATION	A Preliminary Study for INFORMED
NCT06467513	PHASE4	RECRUITING	To Investigate the Effect of Esketamine Hydrochloride on Pulmonary Complications
NCT07252310	PHASE4	ENROLLING_BY_INVITATION	Pilot Study of StudyU for N-of-1 Trials in HFrEF Patients (N-of-1 App)
NCT07454096	PHASE4	NOT_YET_RECRUITING	Application of Radiomics for Diagnosis and Follow-up of Cardiovascular Device Infections: PREDICT Study
NCT00000521	PHASE4	COMPLETED	Sodium-Potassium Blood Pressure Trial in Children
NCT00025766	PHASE4	COMPLETED	Angioplasty and Heart Stents to Treat Individuals With an Occluded Artery Following a Heart Attack
NCT00083772	PHASE4	TERMINATED	Use of Nesiritide in the Management of Acute Diastolic Heart Failure
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00162370	PHASE4	COMPLETED	A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease
NCT00178620	PHASE4	COMPLETED	Pre-hospital Administration of Thrombolytic Therapy With Urgent Culprit Artery Revascularization
NCT00178672	PHASE4	COMPLETED	A Single Center of Carotid Stenting With Distal Protection for the Treatment of Obstructive Carotid Artery Disease
NCT00188747	PHASE4	COMPLETED	Comparison of Three Management Strategies for Post Cardiac Surgery Bleeding
NCT00193999	PHASE4	COMPLETED	Do Nasogastric Tubes After Cardiac Surgery Reduce Nausea and Vomiting
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00296985	PHASE4	COMPLETED	Continuous Cellsaver and Neurocognitive Decline Post Cardiac Surgery
NCT00335582	PHASE4	UNKNOWN	EPIC (Evaluating Perioperative Ischemia Reduction by Clonidine)
NCT00617175	PHASE4	COMPLETED	Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00818337	PHASE4	COMPLETED	Aspirin Responsiveness in Women at Risk for Cardiac Events
NCT00852514	PHASE4	COMPLETED	The Optimization of Blood Pressure and Fluid Status Control With Eight-Polar Bioelectrical Impedance Analysis
NCT00987324	PHASE4	COMPLETED	Efficacy Study of Paclitaxel-eluting Balloon, -Stent vs. Plain Angioplasty for Drug-eluting Stent Restenosis
NCT01346072	PHASE4	COMPLETED	Pilot Study of Using Copeptin to Predict Response to Tolvaptan
NCT01404767	PHASE4	TERMINATED	Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol
NCT01432769	PHASE4	UNKNOWN	Enteral Nutrition After Cardiovascular Surgery
NCT01457586	PHASE4	UNKNOWN	Hemoderivative Imputable Complications in Initial Uncomplicated Heart Surgery
NCT01478061	PHASE4	COMPLETED	Multi-center Assessment of Grafts in Coronaries: Long-term Evaluation of the C-Port Device
NCT01539161	PHASE4	TERMINATED	Reveal Chagas: Clinical Evidence of the Implantable Cardiac Monitor in Patients With Chagas Disease
NCT01823185	PHASE4	UNKNOWN	Bedside Testing of CYP2C19 Gene for Treatment of Patients With PCI With Antiplatelet Therapy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02004613	PHASE4	COMPLETED	Ancillary Effects of Dexmedetomidine Sedation After Cardiac Surgery
NCT02008370	PHASE4	TERMINATED	Exparel in Minimally Invasive Cardiac Surgery
NCT02035007	PHASE4	COMPLETED	Transpulmonary Thermodilution Measurements in Patients With Heart Diseases
NCT02094963	PHASE4	COMPLETED	Safety and Efficacy of Ticagrelor Versus Clopidogrel in Asian/KOREAn Patients With Acute Coronary Syndromes Intended for Invasive Management
NCT02349152	PHASE4	COMPLETED	Remifentanil and Glycemic Response in Cardiac Surgery
NCT02421549	PHASE4	WITHDRAWN	Remote Interrogation in Rural Emergency Departments
NCT02523144	PHASE4	COMPLETED	Dexmedetomidine in Children Having Transthoracic Echocardiography

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IMIPRAMINE	4	6
METOPROLOL	4	6
AMIODARONE	4	5
WARFARIN	4	5
CHOLESTYRAMINE	4	4
LOVASTATIN	4	4
SODIUM CHLORIDE	4	4
SOTALOL	4	4
CLOPIDOGREL	4	3
DEXMEDETOMIDINE	4	3
ESTRADIOL	4	3
QUINIDINE	4	3
ATORVASTATIN	4	2
CETRORELIX	4	2
ASPIRIN	4	1
BUPIVACAINE	4	1
CLONIDINE HYDROCHLORIDE	4	1
ESKETAMINE	4	1
ESMOLOL	4	1
FENTANYL	4	1
MORPHINE SULFATE	4	1
NESIRITIDE	4	1
ORLISTAT	4	1
PACLITAXEL	4	1
REMIFENTANIL	4	1
RETEPLASE	4	1
SEVOFLURANE	4	1
TERIPARATIDE	4	1
TICAGRELOR	4	1
TOLVAPTAN	4	1