Wolff-Parkinson-White syndrome

Summary

Wolff-Parkinson-White syndrome (MONDO:0008685) is a disease caused by PRKAG2 (GenCC Strong), with 52 cohort genes and 8 clinical trials. The dominant Reactome pathway is Muscle contraction (14 cohort genes).

At a glance

• Causal gene: PRKAG2 (GenCC Strong)
• Cohort genes: 52
• ClinVar variants: 202
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Wolff-Parkinson-White syndrome
Mondo ID	MONDO:0008685
EFO	EFO:1001450
MeSH	D014927
OMIM	194200
Orphanet	907
DOID	DOID:384
ICD-11	1091030330
NCIT	C35132
SNOMED CT	17869006
UMLS	C0043202
MedGen	12162
Is cancer (heuristic)	no

Also known as: ventricular familial preexcitation syndrome · Wolff-Parkinson-White pattern (finding) · Wolff-Parkinson-White syndrome · Wolff-Parkinson-white syndrome (disease) · WPW

Data availability: 202 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › Wolff-Parkinson-White syndrome

Related subtypes (9): short QT syndrome, atrioventricular block, sinoatrial node disorder, postural orthostatic tachycardia syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive familial heart block, sinoatrial block, NKX2.5-related congenital, conduction and myopathic heart disease

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

202 retrieved; paginated sample, class counts are floors:

107 uncertain significance, 60 conflicting classifications of pathogenicity, 10 benign/likely benign, 8 benign, 6 likely benign, 4 pathogenic/likely pathogenic, 4 pathogenic, 2 likely pathogenic, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
452250	NM_001232.4(CASQ2):c.2T>C (p.Met1Thr)	CASQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
53090	NM_000218.3(KCNQ1):c.724G>A (p.Asp242Asn)	KCNQ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4075385	NM_001031713.4(MCUR1):c.802C>T (p.Arg268Ter)	MCUR1	Pathogenic	criteria provided, single submitter
6846	NM_016203.4(PRKAG2):c.905G>A (p.Arg302Gln)	PRKAG2	Pathogenic	criteria provided, multiple submitters, no conflicts
4839	NM_000441.2(SLC26A4):c.85G>C (p.Glu29Gln)	SLC26A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438266	NM_001077653.2(TBX20):c.995del (p.Pro332fs)	TBX20	Pathogenic	no assertion criteria provided
487632	NM_003242.6(TGFBR2):c.1563G>A (p.Trp521Ter)	TGFBR2	Pathogenic	criteria provided, single submitter
223300	NM_001267550.2(TTN):c.92683C>T (p.Arg30895Ter)	TTN-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
487597	NM_020297.4(ABCC9):c.2019+2T>C	ABCC9	Likely pathogenic	no assertion criteria provided
487595	NM_001267550.2(TTN):c.66904C>T (p.Leu22302=)	TTN	Likely pathogenic	no assertion criteria provided
487596	NM_005751.5(AKAP9):c.11297G>A (p.Arg3766Gln)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190639	NM_000719.7(CACNA1C):c.1485C>A (p.His495Gln)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190654	NM_000719.7(CACNA1C):c.2579G>A (p.Arg860Gln)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
487613	NM_004415.4(DSP):c.3754G>A (p.Glu1252Lys)	DSP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
465010	NM_001110556.2(FLNA):c.6268G>C (p.Val2090Leu)	FLNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
487622	NM_001458.5(FLNC):c.6748A>C (p.Met2250Leu)	FLNC-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222661	NM_002230.4(JUP):c.578T>C (p.Met193Thr)	JUP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
487584	NM_002230.4(JUP):c.251G>A (p.Arg84Gln)	JUP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
52970	NM_000218.3(KCNQ1):c.1189C>T (p.Arg397Trp)	KCNQ1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192119	NM_001105206.3(LAMA4):c.2398C>T (p.Arg800Cys)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378428	NM_016203.4(PRKAG2):c.750C>T (p.Asp250=)	LOC129999660	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410720	NM_016203.4(PRKAG2):c.704T>G (p.Leu235Arg)	LOC129999660	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45733	NM_016203.4(PRKAG2):c.698C>G (p.Ala233Gly)	LOC129999660	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36601	NM_000256.3(MYBPC3):c.1321G>A (p.Glu441Lys)	MYBPC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14151	NM_002471.4(MYH6):c.3010G>T (p.Ala1004Ser)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
42901	NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr)	MYH7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8269	NM_018055.5(NODAL):c.778G>A (p.Gly260Arg)	NODAL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
487607	NM_022114.4(PRDM16):c.2666C>T (p.Pro889Leu)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167533	NM_016203.4(PRKAG2):c.1304A>G (p.Asn435Ser)	PRKAG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177987	NM_016203.4(PRKAG2):c.*2C>T	PRKAG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 168 · 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
PRKAG2	Strong	Autosomal dominant	Wolff-Parkinson-White syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKAG2	Orphanet:439854	Fatal congenital hypertrophic cardiomyopathy due to glycogen storage 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
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
SNTA1	Orphanet:101016	Romano-Ward syndrome
TBX20	Orphanet:54260	Left ventricular noncompaction
TBX20	Orphanet:99103	Atrial septal defect, ostium secundum type
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
TCAP	Orphanet:154	Familial isolated dilated cardiomyopathy
TCAP	Orphanet:34514	Telethonin-related limb-girdle muscular dystrophy R7
TGFBR2	Orphanet:144	Lynch syndrome
TGFBR2	Orphanet:284973	Marfan syndrome type 2
TGFBR2	Orphanet:60030	Loeys-Dietz syndrome
TGFBR2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR2	Orphanet:99977	Squamous cell carcinoma of the esophagus
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
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome
CACNA1E	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy

Cohort genes → proteins

52 cohort genes, 48 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	52

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRKAG2	HGNC:9386	ENSG00000106617	Q9UGJ0	5’-AMP-activated protein kinase subunit gamma-2	gencc,clinvar
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	clinvar
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
TBX20	HGNC:11598	ENSG00000164532	Q9UMR3	T-box transcription factor TBX20	clinvar
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	clinvar
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	clinvar
TGFBR2	HGNC:11773	ENSG00000163513	P37173	TGF-beta receptor type-2	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
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	clinvar
CACNA1E	HGNC:1392	ENSG00000198216	Q15878	Voltage-dependent R-type calcium channel subunit alpha-1E	clinvar
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	clinvar
CASQ2	HGNC:1513	ENSG00000118729	O14958	Calsequestrin-2	clinvar
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	clinvar
NEBL	HGNC:16932	ENSG00000078114	O76041	Nebulette	clinvar
WWP1	HGNC:17004	ENSG00000123124	Q9H0M0	NEDD4-like E3 ubiquitin-protein ligase WWP1	clinvar
NDE1	HGNC:17619	ENSG00000072864	Q9NXR1	Nuclear distribution protein nudE homolog 1	clinvar
TRPM4	HGNC:17993	ENSG00000130529	Q8TD43	Transient receptor potential cation channel subfamily M member 4	clinvar
TTC39A	HGNC:18657	ENSG00000085831	Q5SRH9	Tetratricopeptide repeat protein 39A	clinvar
RHBDF1	HGNC:20561	ENSG00000007384	Q96CC6	Inactive rhomboid protein 1	clinvar
MCUR1	HGNC:21097	ENSG00000050393	Q96AQ8	Mitochondrial calcium uniporter regulator 1	clinvar
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar
RBM20	HGNC:27424	ENSG00000203867	Q5T481	RNA-binding protein 20	clinvar
GPD1L	HGNC:28956	ENSG00000152642	Q8N335	Glycerol-3-phosphate dehydrogenase 1-like protein	clinvar
FNIP1	HGNC:29418	ENSG00000217128	Q8TF40	Folliculin-interacting protein 1	clinvar
DPP6	HGNC:3010	ENSG00000130226	P42658	A-type potassium channel modulatory protein DPP6	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	clinvar
AKAP9	HGNC:379	ENSG00000127914	Q99996	A-kinase anchor protein 9	clinvar
GJA5	HGNC:4279	ENSG00000265107	P36382	Gap junction alpha-5 protein	clinvar
TTN-AS1	HGNC:44124	ENSG00000237298		TTN antisense RNA 1	clinvar
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	clinvar
MHRT	HGNC:51291			myosin heavy chain associated RNA transcript	clinvar
FLNC-AS1	HGNC:53474	ENSG00000242902		FLNC antisense RNA 1	clinvar
GJD2-DT	HGNC:55560	ENSG00000250007		GJD2 divergent transcript	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
KCNJ2	HGNC:6263	ENSG00000123700	P63252	Inward rectifier potassium channel 2	clinvar
KCNQ1	HGNC:6294	ENSG00000053918	P51787	Potassium voltage-gated channel subfamily KQT member 1	clinvar
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	clinvar
LAMC1	HGNC:6492	ENSG00000135862	P11047	Laminin subunit gamma-1	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	clinvar
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	clinvar
MYH7	HGNC:7577	ENSG00000092054	P12883	Myosin-7	clinvar
NODAL	HGNC:7865	ENSG00000156574	Q96S42	Nodal homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKAG2	5’-AMP-activated protein kinase subunit gamma-2	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism.
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.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
TBX20	T-box transcription factor TBX20	Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
TCAP	Telethonin	Muscle assembly regulating factor.
TGFBR2	TGF-beta receptor type-2	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
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.
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CACNA1E	Voltage-dependent R-type calcium channel subunit alpha-1E	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells.
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
CASQ2	Calsequestrin-2	Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
NEBL	Nebulette	Binds to actin and plays an important role in the assembly of the Z-disk.
WWP1	NEDD4-like E3 ubiquitin-protein ligase WWP1	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
NDE1	Nuclear distribution protein nudE homolog 1	Required for centrosome duplication and formation and function of the mitotic spindle.
TRPM4	Transient receptor potential cation channel subfamily M member 4	Calcium-activated selective cation channel that mediates membrane depolarization.
RHBDF1	Inactive rhomboid protein 1	Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation.
MCUR1	Mitochondrial calcium uniporter regulator 1	Key regulator of mitochondrial calcium uniporter (MCU) required for calcium entry into mitochondrion.
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
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.
GPD1L	Glycerol-3-phosphate dehydrogenase 1-like protein	Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium c…
FNIP1	Folliculin-interacting protein 1	Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3.
DPP6	A-type potassium channel modulatory protein DPP6	Promotes cell surface expression of the potassium channel KCND2.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
AKAP9	A-kinase anchor protein 9	Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus.
GJA5	Gap junction alpha-5 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
ANK2	Ankyrin-2	Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells.
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.
KCNJ2	Inward rectifier potassium channel 2	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
KCNQ1	Potassium voltage-gated channel subfamily KQT member 1	Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon.
LAMA4	Laminin subunit alpha-4	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LAMC1	Laminin subunit gamma-1	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
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.
MYH6	Myosin-6	Muscle contraction.
MYH7	Myosin-7	Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction.
NODAL	Nodal homolog	Essential for mesoderm formation and axial patterning during embryonic development.
SLC26A4	Pendrin	Sodium-independent transporter of chloride and iodide.
PITX2	Pituitary homeobox 2	May play a role in myoblast differentiation.

Protein-family classification

Druggable: 17 · Difficult: 12 · Unknown: 23 · 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	8	17.2×	2e-07
Scaffold/PPI	7	2.3×	0.117
Transporter	2	3.0×	0.384
Antibody/Immunoglobulin	3	1.7×	0.527
Protease	2	1.4×	0.668
Kinase	2	1.1×	0.752
Transcription factor	5	0.8×	0.881
Other/Unknown	23	0.8×	0.966

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKAG2	Other/Unknown	no		CBS_dom, CBS_dom_sf, AMPK_gamma/SDS23_families
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
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
TBX20	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf
TGFBR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
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
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNA1E	Ion channel	yes		EF_hand_dom, VDCCAlpha1, VDCC_R_a1su
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
CASQ2	Other/Unknown	no		Calsequestrin, Calsequestrin_CS, Thioredoxin-like_sf
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
NEBL	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulette_SH3
WWP1	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom
NDE1	Other/Unknown	no		NUDE_dom, NUDE
TRPM4	Ion channel	yes		Ion_trans_dom, TRPM_SLOG, TRPM
TTC39A	Other/Unknown	no		TPR-like_helical_dom_sf, IML2/TPR_39, TPR_rpt
RHBDF1	Protease	yes		iRhom1_2_N, Peptidase_S54_rhomboid_dom, Rhomboid-like_sf
MCUR1	Other/Unknown	no		CCDC90-like
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
RBM20	Transcription factor	no		RRM_dom, Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2
GPD1L	Other/Unknown	no		G3P_DH_NAD-dep_C, G3P_DH_NAD-dep, 6-PGluconate_DH-like_C_sf
FNIP1	Other/Unknown	no		FNIP_fam, FNIP_N_dom, FNIP_mid_dom
DPP6	Protease	yes		Peptidase_S9_cat, Peptidase_S9B_N, AB_hydrolase_fold
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
AKAP9	Other/Unknown	no		ELK_dom, PACT_domain, AKAP9/Pericentrin
GJA5	Other/Unknown	no		Connexin, Connexin40, Connexin_N
TTN-AS1	Other/Unknown	no
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
MHRT	Other/Unknown	no
FLNC-AS1	Other/Unknown	no
GJD2-DT	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
KCNJ2	Ion channel	yes		K_chnl_inward-rec_Kir2.1, K_chnl_inward-rec_Kir_cyto, K_chnl_inward-rec_Kir_N
KCNQ1	Ion channel	yes		K_chnl_volt-dep_KCNQ, Ion_trans_dom, K_chnl_volt-dep_KCQN1
LAMA4	Other/Unknown	no		EGF, Laminin_G, LE_dom
LAMC1	Other/Unknown	no		Laminin_IV, EGF, LE_dom
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
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
NODAL	Other/Unknown	no		TGF-b_C, TGF-beta-like, TGFb_CS

Expression context

Cohort genes with no expression data: 1.

47 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)	51
unknown	1

Top tissues across cohort

Tissue	Cohort genes
apex of heart	11
hindlimb stylopod muscle	8
right atrium auricular region	7
cardiac atrium	6
cardiac muscle of right atrium	6
left ventricle myocardium	5
myocardium	5
skeletal muscle tissue of biceps brachii	5
heart right ventricle	4
gastrocnemius	4
skeletal muscle tissue of rectus abdominis	4
biceps brachii	4
right coronary artery	3
heart left ventricle	2
tendon of biceps brachii	2
parietal pleura	2
Brodmann (1909) area 23	2
cortical plate	2
middle temporal gyrus	2
popliteal artery	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKAG2	258	ubiquitous	marker	right atrium auricular region, cardiac atrium, cardiac muscle of right atrium
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
TBX20	52	broad	marker	right atrium auricular region, cardiac atrium, heart
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
TGFBR2	289	ubiquitous	marker	pericardium, tibia, parietal pleura
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
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CACNA1E	144	broad	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23
PRDM16	202	broad	marker	sural nerve, pigmented layer of retina, ascending aorta
CASQ2	213	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
ACTN2	226	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle
NEBL	282	broad	marker	heart right ventricle, myocardium, cranial nerve II
WWP1	301	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, biceps brachii
NDE1	134	ubiquitous	marker	colonic epithelium, ventricular zone, corpus callosum
TRPM4	201	ubiquitous	marker	mucosa of transverse colon, rectum, apex of heart
TTC39A	239	broad	marker	islet of Langerhans, right testis, sperm
RHBDF1	266	ubiquitous	marker	tibial nerve, popliteal artery, tibial artery
MCUR1	288	ubiquitous	marker	jejunal mucosa, decidua, amniotic fluid
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii
RBM20	191	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
GPD1L	297	ubiquitous	marker	biceps brachii, heart right ventricle, skeletal muscle tissue of biceps brachii
FNIP1	257	ubiquitous	marker	cardiac muscle of right atrium, left ventricle myocardium, myocardium
DPP6	221	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 75.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
ANK2	6,423
TGFBR2	5,777
FLNA	5,321
JUP	4,618
VCL	4,495
TTN	4,237
AKAP9	3,537
KCNQ1	3,235
PRKAG2	3,212

Intra-cohort edges

A	B	Sources
ABCC9	ACTN2	string_interaction
ABCC9	MYBPC3	string_interaction
ABCC9	RBM20	string_interaction
ABCC9	SCN5A	string_interaction
ABCC9	TCAP	string_interaction
ACTN2	CACNA1C	biogrid_interaction
ACTN2	MYH6	biogrid_interaction, string_interaction
ACTN2	MYH7	biogrid_interaction, string_interaction
ACTN2	NEBL	string_interaction
ACTN2	TCAP	string_interaction
ACTN2	TNNT2	string_interaction
ACTN2	TTN	string_interaction
ACTN2	VCL	string_interaction
AKAP9	KCNH2	string_interaction
AKAP9	KCNQ1	biogrid_interaction, intact, string_interaction
AKAP9	SNTA1	string_interaction
ANK2	CACNA1E	string_interaction
ANK2	TTN	string_interaction
CACNA1C	CASQ2	string_interaction
CACNA1C	GPD1L	string_interaction
CACNA1C	KCNH2	string_interaction
CACNA1C	RYR2	biogrid_interaction, string_interaction
CASQ2	KCNH2	string_interaction
CASQ2	RYR2	string_interaction
CASQ2	SCN5A	string_interaction
COL5A1	LAMC1	string_interaction
DPP6	SCN5A	string_interaction
DSP	JUP	intact, string_interaction
FLNA	KCNJ2	intact
FLNA	VCL	string_interaction
FLNC	MYBPC3	intact
FLNC	NEBL	string_interaction
FLNC	TCAP	string_interaction
FLNC	VCL	string_interaction
GJA5	SCN5A	string_interaction
GJA5	TBX5	string_interaction
GPD1L	SCN5A	intact, string_interaction
JUP	LMNA	string_interaction
JUP	RYR2	string_interaction
KCNH2	KCNQ1	string_interaction
KCNH2	SCN5A	string_interaction
KCNQ1	SCN5A	string_interaction
LAMA4	LAMC1	string_interaction
LMNA	TTC39A	biogrid_interaction
MYBPC3	MYH6	string_interaction
MYBPC3	MYH7	intact, string_interaction
MYBPC3	PRKAG2	string_interaction
MYBPC3	RBM20	string_interaction
MYBPC3	TCAP	string_interaction
MYBPC3	TNNT2	string_interaction

Structural data

PDB: 36 · AlphaFold-only: 12 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
MYH7	P12883	43
VCL	P18206	37
CACNA1C	Q13936	33
TRPM4	Q8TD43	29
KCNQ1	P51787	28
LMNA	P02545	28
RYR2	Q92736	26
FLNA	P21333	26
TNNT2	P45379	25
KCNH2	Q12809	24
TGFBR2	P37173	22
MYBPC3	Q14896	17
SCN5A	Q14524	16
ACTN2	P35609	16
FLNC	Q14315	14
ANK2	Q01484	11
WWP1	Q9H0M0	8
DPP6	P42658	8
CACNA1E	Q15878	5
TBX5	Q99593	4
CASQ2	O14958	4
DSP	P15924	4
LAMC1	P11047	4
KCNJ2	P63252	3
PITX2	Q99697	3
TCAP	O15273	2
PRDM16	Q9HAZ2	2
RHBDF1	Q96CC6	2
NEBL	O76041	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TTC39A	Q5SRH9	87.50
SLC26A4	O43511	82.72
ABCC9	O60706	81.72
SNTA1	Q13424	80.00
MYH6	P13533	74.91
LAMA4	Q16363	73.75
MCUR1	Q96AQ8	70.82
GJA5	P36382	70.35
TBX20	Q9UMR3	67.87
PRKAG2	Q9UGJ0	67.24
RBM20	Q5T481	48.52
AKAP9	Q99996

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 235. Enrichment computed across 52 evidence-associated genes (41 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 41 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Muscle contraction	14	26.4×	1e-14	RYR2, SCN5A, TBX5, TCAP, CACNA1C, CASQ2, ACTN2, AKAP9 (+6 more)
Cardiac conduction	10	26.5×	3e-10	RYR2, SCN5A, TBX5, CACNA1C, CASQ2, AKAP9, ABCC9, KCNH2 (+2 more)
Striated Muscle Contraction	6	45.2×	2e-07	TCAP, TNNT2, TTN, ACTN2, MYBPC3, MYH6
Phase 3 - rapid repolarisation	3	83.6×	3e-04	AKAP9, KCNH2, KCNQ1
Phase 2 - plateau phase	3	55.7×	9e-04	CACNA1C, AKAP9, KCNQ1
Neuronal System	7	7.6×	0.001	PRKAG2, CACNA1E, ACTN2, ABCC9, KCNH2, KCNJ2, KCNQ1
Attachment of bacteria to epithelial cells	3	36.3×	0.002	COL5A1, LAMA4, LAMC1
Non-integrin membrane-ECM interactions	4	15.1×	0.004	SNTA1, COL5A1, LAMA4, LAMC1
MET activates PTK2 signaling	3	27.9×	0.004	COL5A1, LAMA4, LAMC1
Potassium Channels	4	13.1×	0.006	ABCC9, KCNH2, KCNJ2, KCNQ1
Formation of the dystrophin-glycoprotein complex (DGC)	3	22.6×	0.007	SNTA1, LAMA4, LAMC1
Developmental Lineage of Pancreatic Ductal Cells	3	16.7×	0.015	COL5A1, LAMA4, LAMC1
Regulation of CDH1 Function	2	46.4×	0.015	VCL, JUP
Ion homeostasis	3	14.9×	0.018	RYR2, CASQ2, ABCC9
Platelet degranulation	4	8.6×	0.018	TTN, VCL, ACTN2, FLNA
Inwardly rectifying K+ channels	2	34.8×	0.021	ABCC9, KCNJ2
Cell-extracellular matrix interactions	2	32.8×	0.022	FLNA, FLNC
Integration of energy metabolism	3	12.9×	0.022	PRKAG2, CACNA1C, CACNA1E
Signaling by BRAF and RAF1 fusions	3	12.5×	0.022	VCL, AKAP9, LMNA
MET promotes cell motility	2	29.3×	0.023	LAMA4, LAMC1
Transmission across Chemical Synapses	4	7.4×	0.023	PRKAG2, CACNA1E, ACTN2, KCNJ2
ECM proteoglycans	3	11.0×	0.027	COL5A1, LAMA4, LAMC1
Stimuli-sensing channels	3	9.9×	0.034	RYR2, CASQ2, WWP1
Defective SLC26A4 causes Pendred syndrome (PDS)	1	278.5×	0.035	SLC26A4
Cardiogenesis	2	20.6×	0.039	TBX20, TBX5
L1CAM interactions	3	8.8×	0.043	SCN5A, ANK2, LAMC1
Laminin interactions	2	18.6×	0.045	LAMA4, LAMC1
Interaction between L1 and Ankyrins	2	18.0×	0.046	SCN5A, ANK2
Phase 0 - rapid depolarisation	2	16.9×	0.050	SCN5A, CACNA1C
TGFBR2 MSI Frameshift Mutants in Cancer	1	139.3×	0.052	TGFBR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 47 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	11	93.9×	6e-17	RYR2, SCN5A, TCAP, TNNT2, TTN, CASQ2, KCNH2, KCNQ1 (+3 more)
regulation of heart rate by cardiac conduction	11	87.7×	7e-17	SCN5A, CACNA1C, TRPM4, DSP, AKAP9, GJA5, ANK2, JUP (+3 more)
ventricular cardiac muscle cell action potential	8	168.7×	1e-14	RYR2, SCN5A, SNTA1, GPD1L, GJA5, ANK2, KCNH2, KCNQ1
regulation of ventricular cardiac muscle cell membrane repolarization	7	125.5×	8e-12	SCN5A, SNTA1, AKAP9, GJA5, ANK2, KCNH2, KCNQ1
regulation of heart rate	8	79.7×	8e-12	RYR2, SCN5A, SNTA1, CASQ2, GPD1L, ANK2, MYH6, MYH7
sarcomere organization	7	57.0×	3e-09	TCAP, TNNT2, TTN, ACTN2, FLNC, MYBPC3, MYH6
regulation of ventricular cardiac muscle cell action potential	5	149.4×	1e-08	RYR2, CACNA1C, TRPM4, DSP, JUP
regulation of membrane repolarization	5	137.9×	1e-08	CASQ2, AKAP9, KCNH2, KCNJ2, KCNQ1
muscle filament sliding	5	112.0×	4e-08	TCAP, TNNT2, TTN, MYH6, MYH7
striated muscle contraction	5	89.6×	1e-07	RYR2, TTN, CASQ2, MYH6, MYH7
regulation of atrial cardiac muscle cell action potential	3	358.6×	1e-06	RYR2, GJA5, ANK2
regulation of cardiac muscle cell contraction	4	95.6×	4e-06	SCN5A, ANK2, KCNJ2, MYBPC3
positive regulation of potassium ion transmembrane transport	4	84.4×	6e-06	FLNA, KCNH2, KCNJ2, KCNQ1
membrane depolarization during AV node cell action potential	3	215.1×	9e-06	SCN5A, CACNA1C, TRPM4
regulation of ventricular cardiac muscle cell membrane depolarization	3	179.3×	2e-05	SCN5A, GPD1L, GJA5
SA node cell action potential	3	179.3×	2e-05	SCN5A, GJA5, ANK2
ventricular cardiac muscle tissue morphogenesis	4	59.8×	2e-05	TNNT2, MYBPC3, MYH6, MYH7
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	4	57.4×	2e-05	RYR2, CACNA1C, CASQ2, ANK2
cardiac muscle cell development	4	53.1×	3e-05	TCAP, TTN, ACTN2, MYH6
regulation of atrial cardiac muscle cell membrane depolarization	3	119.5×	6e-05	SCN5A, TBX5, GJA5
cardiac muscle hypertrophy	3	107.6×	7e-05	RYR2, TCAP, TTN
membrane repolarization during action potential	3	107.6×	7e-05	KCNH2, KCNJ2, KCNQ1
membrane repolarization during cardiac muscle cell action potential	3	107.6×	7e-05	KCNH2, KCNJ2, KCNQ1
atrial cardiac muscle cell action potential	3	107.6×	7e-05	SCN5A, ANK2, KCNQ1
muscle contraction	5	22.1×	8e-05	SNTA1, TBX20, TTN, MYH6, MYH7
cardiac muscle tissue morphogenesis	3	89.6×	1e-04	TBX20, TCAP, TTN
membrane depolarization during cardiac muscle cell action potential	3	89.6×	1e-04	SCN5A, CACNA1C, KCNJ2
cell communication by electrical coupling involved in cardiac conduction	3	89.6×	1e-04	RYR2, CACNA1C, GJA5
atrial septum morphogenesis	3	82.7×	1e-04	TBX20, TBX5, GJA5
pulmonary valve formation	2	358.6×	1e-04	TBX20, GJA5

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Adenosine	Approved (phase 4)

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 9 · Phased (≥1): 11 · Undrugged: 41

Druggability breadth: 27 of 52 evidence-associated genes (52%) 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
PRKAG2	ADENOSINE PHOSPHATE
SCN5A	BEPRIDIL
TGFBR2	PONATINIB
CACNA1C	REMIFENTANIL
CACNA1E	NIMODIPINE
ABCC9	PINACIDIL ANHYDROUS
KCNH2	CETIRIZINE
KCNQ1	AMBRISENTAN
LMNA	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
KCNH2	706	4
SCN5A	108	4
CACNA1C	85	4
TGFBR2	22	4
PRKAG2	19	4
KCNQ1	15	4
ABCC9	5	4
CACNA1E	2	4
RYR2	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADENOSINE PHOSPHATE	4	KCNH2, PRKAG2
CAPIVASERTIB	4	PRKAG2
SUNITINIB	4	CACNA1C, KCNH2, KCNQ1, LMNA, PRKAG2, SCN5A
MIDOSTAURIN	4	PRKAG2
BEPRIDIL	4	CACNA1C, KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, LMNA, SCN5A
IMIPRAMINE	4	CACNA1C, KCNH2, LMNA, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A, TGFBR2
DULOXETINE	4	CACNA1C, KCNH2, KCNQ1, SCN5A
PALONOSETRON	4	KCNH2, KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN5A
FEDRATINIB	4	KCNH2, SCN5A, TGFBR2
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCNH2, KCNQ1, SCN5A
DARIFENACIN	4	KCNH2, KCNQ1, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	CACNA1C, KCNH2, KCNQ1, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, LMNA, SCN5A
NIMODIPINE	4	CACNA1C, CACNA1E, LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
PRKAG2	266	Binding:265, Functional:1
TGFBR2	188	Binding:188
KCNQ1	179	Binding:96, Functional:64, ADMET:14, Toxicity:5
ABCC9	61	Functional:46, Binding:15
SLC26A4	37	Binding:37
KCNJ2	31	Binding:23, ADMET:8
RYR2	15	Binding:15
CACNA1E	14	Binding:14
TRPM4	14	Binding:13, Functional:1
LMNA	12	Binding:9, Functional:3
FLNA	7	Binding:7
FNIP1	3	Binding:3
TNNT2	2	Binding:2
VCL	2	Binding:2
PRDM16	2	Binding:2
DSP	2	Binding:2
TBX5	1	Binding:1
TTN	1	Binding:1
JUP	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGFBR2	2.7.10.2	non-specific protein-tyrosine kinase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
WWP1	2.3.2.26	HECT-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRKAG2	266
SCN5A	594
TGFBR2	188
CACNA1C	575
KCNH2	4,851
KCNQ1	179

Pharmacogenomics

Cohort genes with a PharmGKB record: 48; 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)
ADENOSINE PHOSPHATE	4	KCNH2, PRKAG2
CAPIVASERTIB	4	PRKAG2
SUNITINIB	4	CACNA1C, KCNH2, KCNQ1, LMNA, PRKAG2, SCN5A
MIDOSTAURIN	4	PRKAG2
BEPRIDIL	4	CACNA1C, KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, LMNA, SCN5A
IMIPRAMINE	4	CACNA1C, KCNH2, LMNA, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A, TGFBR2
DULOXETINE	4	CACNA1C, KCNH2, KCNQ1, SCN5A
PALONOSETRON	4	KCNH2, KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN5A
FEDRATINIB	4	KCNH2, SCN5A, TGFBR2
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCNH2, KCNQ1, SCN5A
DARIFENACIN	4	KCNH2, KCNQ1, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	CACNA1C, KCNH2, KCNQ1, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, LMNA, SCN5A
NIMODIPINE	4	CACNA1C, CACNA1E, LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	PRKAG2, SCN5A, TGFBR2, CACNA1C, CACNA1E, ABCC9, KCNH2, KCNQ1, LMNA
B	Phased (≥1) drug, not yet approved	2	RYR2, FLNA
C	Druggable family + PDB, no drug	7	TTN, TRPM4, RHBDF1, DPP6, FLNC, KCNJ2, MYBPC3
D	Druggable family + AlphaFold only, no drug	1	SLC26A4
E	Difficult family or no structure, no drug	33	SNTA1, TBX20, TBX5, TCAP, TNNT2, VCL, PRDM16, CASQ2, ACTN2, NEBL (+23 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SNTA1	0	SCN5A
CASQ2	0	RYR2, CACNA1C
RBM20	0	ABCC9
GPD1L	0	SCN5A
DPP6	0	SCN5A
AKAP9	0	KCNQ1
GJA5	0	SCN5A
TBX20	0	—
TBX5	1	—
TCAP	0	—
TNNT2	2	—
TTN	1	—
VCL	2	—
PRDM16	2	—
ACTN2	0	—
NEBL	0	—
WWP1	0	—
NDE1	0	—
TRPM4	14	—
TTC39A	0	—
RHBDF1	0	—
MCUR1	0	—
COL5A1	0	—
FNIP1	3	—
DSP	2	—
FLNC	0	—
TTN-AS1	0	—
ANK2	0	—
MHRT	0	—
FLNC-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07435181	Not specified	NOT_YET_RECRUITING	Comparative Outcomes of Radiofrequency Ablation of Concealed and Manifest Accessory Pathways: a Single Center, Retrospective Observational Study
NCT00251121	Not specified	COMPLETED	Routine Mini-invasive Electrophysiology Study for Patients Feeling Tachycardia, With a Negative Holter ECG
NCT00873470	Not specified	TERMINATED	Wolff-Parkinson-White Syndrome Anterograde Refractory Period of Accessory Duct
NCT03207373	Not specified	TERMINATED	Stress ECG Test for the Evaluation of the Risk of Sudden Cardiac Death in a Paediatric Cohort With WPW Pattern
NCT03301935	Not specified	COMPLETED	Risk Assessment in Patients With Symptomatic- and Asymptomatic Preexcitation
NCT03816033	Not specified	UNKNOWN	Cryotherapy Versus Radiofrequency Catheter Ablation Research Program
NCT04106622	Not specified	UNKNOWN	Accessory Pathway Antegrade Effective Refractory Period Among WPW Patients: the Risk in Relation to the Location
NCT06349109	Not specified	COMPLETED	Physical Activity in Children With Wolff-Parkinson-White Syndrome