Brugada syndrome

disease

On this page

Also known as Brugada type idiopathic ventricular fibrillationidiopathic ventricular fibrillation, Brugada typeright bundle branch block, ST segment elevation, and sudden death syndromesudden unexpected nocturnal death syndromesudden unexplained nocturnal death syndrome

Summary

Brugada syndrome (MONDO:0015263) is a disease (an umbrella term covering 9 Mondo subtypes) with 66 cohort genes (49 GWAS associations across 5 studies) and 43 clinical trials. The dominant Reactome pathway is Muscle contraction (22 cohort genes). Top therapeutic interventions include flecainide, empagliflozin, and procainamide.

At a glance

Prevalence: 1-5 / 10 000 (Europe)
Umbrella term: 9 Mondo subtypes
Cohort genes: 66
GWAS associations: 49
ClinVar variants: 3,797
Phenotypes (HPO): 12
Clinical trials: 43

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	20	Europe	Not yet validated
Point prevalence	6-9 / 10 000	75	South East Asia	Not yet validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0001279	Syncope	Frequent (30-79%)
HP:0001695	Cardiac arrest	Frequent (30-79%)
HP:0011712	Right bundle branch block	Frequent (30-79%)
HP:0012251	ST segment elevation	Frequent (30-79%)
HP:0001649	Tachycardia	Occasional (5-29%)
HP:0001663	Ventricular fibrillation	Occasional (5-29%)
HP:0004751	Paroxysmal ventricular tachycardia	Occasional (5-29%)
HP:0004755	Supraventricular tachycardia	Occasional (5-29%)
HP:0011704	Sick sinus syndrome	Occasional (5-29%)
HP:0011705	First degree atrioventricular block	Occasional (5-29%)
HP:0004308	Ventricular arrhythmia	Very rare (<1-4%)
HP:0011715	Trifascicular block	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Brugada syndrome
Mondo ID	MONDO:0015263
MeSH	D053840
OMIM	601144
Orphanet	130
DOID	DOID:0050451
ICD-11	1250136584
NCIT	C142891
SNOMED CT	418818005
UMLS	C1142166
MedGen	222975
GARD	0001030
MedDRA	10059027
NORD	878
Is cancer (heuristic)	no

Also known as: Brugada syndrome · Brugada type idiopathic ventricular fibrillation · idiopathic ventricular fibrillation, Brugada type · right bundle branch block, ST segment elevation, and sudden death syndrome · sudden unexpected nocturnal death syndrome · sudden unexplained nocturnal death syndrome

Data availability: 3,797 ClinVar variants · 49 GWAS associations (5 studies) · 29 GenCC gene-disease records · 36 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Subtypes (9): Brugada syndrome 1, Brugada syndrome 2, Brugada syndrome 3, Brugada syndrome 4, Brugada syndrome 5, Brugada syndrome 6, Brugada syndrome 7, Brugada syndrome 8, Brugada syndrome 9

Genetics & variants

GWAS landscape

49 GWAS associations across 5 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6801957	6e-217	SCN10A	C	0.41
rs10428132	1e-68	SCN10A	T	2.55
rs7374540	4e-57	SCN5A	C	1.72
rs3757217	4e-57	HEY2, HEY2-AS1	C	1.58
rs6782237	1e-47	SCN5A - SCN10A	C	1.74
rs9398791	1e-39	NCOA7	C	1.53
rs7433206	1e-23	SCN5A	A	1.48
rs34760424	3e-23	SCN5A	G	2.32
rs9388446	2e-21	HEY2-AS1	A	1.85
rs9388451	5e-17	HEY2 - NCOA7	C	1.58
rs6810361	4e-16	EXOG	C	1.7
rs41310232	1e-15	SCN5A	A	1.56
rs11708996	1e-14	SCN5A	C	1.73
rs62241190	9e-14	SCN5A	G	1.96
rs72671655	3e-13	ZFPM2	T	1.85
rs16835523	3e-13	ZSCAN20	G	0.77
rs883079	3e-13	TBX5	T	0.8
rs72622262	2e-12	LINC02183 - CRNDE	G	0.77
rs76267029	3e-11	TBX20 - HERPUD2	G	1.31
rs11765936	4e-11	TBX20 - HERPUD2	G	1.37
rs476348	6e-11	MAPRE2	C	1.25
rs7105159	8e-11	WT1-AS	T	1.31
rs6767797	3e-10	EXOG	G	2.3
rs804281	1e-09	GATA4	G	1.22
rs11645463	1e-09	LINC02140 - LINC02183	A	1.22
rs340398	2e-09	TBX20 - HERPUD2	C	1.22
rs72905083	2e-09	WT1-AS	A	1.43
rs133902	5e-09	MYO18B	T	1.2
rs2593619	7e-09	USP34	G	1.19
rs3734634	8e-09	NCOA7	A	2.5

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90086158	Barc J	2022	2,820	10,001	Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.
GCST90295916	Ishikawa T	2024	940	1,634	Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.
GCST90295917	Ishikawa T	2024	940	1,634	Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.
GCST002098	Bezzina CR	2013	312	1,115	Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.
GCST011054	Makarawate P	2020	154	0	Common and rare susceptibility genetic variants predisposing to Brugada Syndrome in Thailand.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	4
Tier 3: regulatory	1
Tier 4: intronic/intergenic	33

MAF distribution

Bucket	Variants
common (>=0.05)	37
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	5
3_prime_UTR_variant	2
regulatory_region_variant	1
non_coding_transcript_exon_variant	1
splice_region_variant	1
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6801957	3	38725824	T>A,C,G	0.47	intron_variant	SCN10A	6e-217	Tier 4: intronic/intergenic
rs10428132	3	38736063	T>A,C,G	0.41	intron_variant	SCN10A	1e-68	Tier 4: intronic/intergenic
rs7374540	3	38592651	C>A,G	0.39	intron_variant	SCN5A	4e-57	Tier 4: intronic/intergenic
rs3757217	6	125748490	G>A,C,T	0.464	intron_variant	HEY2, HEY2-AS1	4e-57	Tier 4: intronic/intergenic
rs6782237	3	38655062	G>A,C	0.32	intergenic_variant	SCN5A - SCN10A	1e-47	Tier 4: intronic/intergenic
rs9398791	6	125794675	T>A,C	0.49	intron_variant	NCOA7	1e-39	Tier 4: intronic/intergenic
rs7433206	3	38616217	T>A	0.42	intron_variant	SCN5A	1e-23	Tier 4: intronic/intergenic
rs34760424	3	38641527	G>T	0.06	intron_variant	SCN5A	3e-23	Tier 4: intronic/intergenic
rs9388446	6	125743774	T>A,C	0.373	intron_variant	HEY2-AS1	2e-21	Tier 4: intronic/intergenic
rs9388451	6	125769231	T>A,C,G	0.5	intergenic_variant	HEY2 - NCOA7	5e-17	Tier 4: intronic/intergenic
rs6810361	3	38533477	T>C	0.417	regulatory_region_variant	EXOG	4e-16	Tier 3: regulatory
rs41310232	3	38647751	G>A	0.09	intron_variant	SCN5A	1e-15	Tier 4: intronic/intergenic
rs11708996	3	38592432	G>C	0.15	intron_variant	SCN5A	1e-14	Tier 4: intronic/intergenic
rs62241190	3	38565977	A>G	0.03	intron_variant	SCN5A	9e-14	Tier 4: intronic/intergenic
rs72671655	8	105335669	T>A	0.05	intron_variant	ZFPM2	3e-13	Tier 4: intronic/intergenic
rs16835523	1	33501482	C>G,T	0.16	3_prime_UTR_variant	ZSCAN20	3e-13	Tier 2: splice/UTR
rs883079	12	114355435	C>A,G,T	0.296	3_prime_UTR_variant	TBX5	3e-13	Tier 2: splice/UTR
rs72622262	16	54629032	C>A,G,T	0.159	non_coding_transcript_exon_variant	LINC02183 - CRNDE	2e-12	Tier 4: intronic/intergenic
rs76267029	7	35265873	A>C,G	0.176	intergenic_variant	TBX20 - HERPUD2	3e-11	Tier 4: intronic/intergenic
rs11765936	7	35309535	T>A,G	0.15	intergenic_variant	TBX20 - HERPUD2	4e-11	Tier 4: intronic/intergenic
rs476348	18	35090057	T>A,C,G	0.301	intron_variant	MAPRE2	6e-11	Tier 4: intronic/intergenic
rs7105159	11	32459913	G>T	0.164	intron_variant	WT1-AS	8e-11	Tier 4: intronic/intergenic
rs6767797	3	38541080	A>G,T	0.44	intergenic_variant	EXOG	3e-10	Tier 4: intronic/intergenic
rs804281	8	11754356	A>G,T	0.42	intron_variant	GATA4	1e-09	Tier 4: intronic/intergenic
rs11645463	16	54422441	A>G	0.46	intron_variant	LINC02140 - LINC02183	1e-09	Tier 4: intronic/intergenic
rs340398	7	35374178	C>G,T	0.38	intron_variant	TBX20 - HERPUD2	2e-09	Tier 4: intronic/intergenic
rs72905083	11	32452828	G>A	0.08	intron_variant	WT1-AS	2e-09	Tier 4: intronic/intergenic
rs133902	22	25768112	C>A,G,T	0.438	splice_region_variant	MYO18B	5e-09	Tier 2: splice/UTR
rs2593619	2	61385869	A>G,T	0.381	intron_variant	USP34	7e-09	Tier 4: intronic/intergenic
rs3734634	6	125790654	G>A,C,T	0.32	5_prime_UTR_variant	NCOA7	8e-09	Tier 2: splice/UTR

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

346 uncertain significance, 165 likely benign, 56 conflicting classifications of pathogenicity, 14 benign/likely benign, 8 benign, 6 pathogenic, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069871	NC_000003.11:g.(?38655228)(38663986_?)del	SCN5A	Pathogenic	criteria provided, single submitter
1072847	NM_000335.5(SCN5A):c.934+1G>A	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
1074266	NC_000003.11:g.(?38674520)(38674804_?)del	SCN5A	Pathogenic	criteria provided, single submitter
1076513	NM_000335.5(SCN5A):c.901del (p.Trp301fs)	SCN5A	Pathogenic	criteria provided, multiple submitters, no conflicts
1299249	NM_000335.5(SCN5A):c.4313dup (p.Trp1439fs)	SCN5A	Pathogenic	no assertion criteria provided
132906	NM_000335.5(SCN5A):c.3960+1G>A	SCN5A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459394	NC_000003.11:g.(?38591802)(38674808_?)del	SCN5A	Pathogenic	criteria provided, single submitter
1066904	NC_000003.11:g.(?38591792)(38593069_?)del	SCN5A	Likely pathogenic	criteria provided, single submitter
1326907	NM_000335.5(SCN5A):c.3821A>G (p.Asp1274Gly)	SCN5A	Likely pathogenic	no assertion criteria provided
1326908	NM_000335.5(SCN5A):c.935-3C>G	SCN5A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1326912	NM_000335.5(SCN5A):c.4810+5G>A	SCN5A	Likely pathogenic	criteria provided, single submitter
1015295	NM_000722.4(CACNA2D1):c.2060C>T (p.Ala687Val)	CACNA2D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044068	NM_000722.4(CACNA2D1):c.1405A>G (p.Ile469Val)	CACNA2D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1364338	NM_000722.4(CACNA2D1):c.394G>T (p.Asp132Tyr)	CACNA2D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1399290	NM_000722.4(CACNA2D1):c.2324C>A (p.Ala775Asp)	CACNA2D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005323	NM_015141.4(GPD1L):c.344C>T (p.Ala115Val)	GPD1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1041106	NM_015141.4(GPD1L):c.619-9C>A	GPD1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054485	NM_015141.4(GPD1L):c.944A>G (p.Lys315Arg)	GPD1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056227	NM_015141.4(GPD1L):c.376del (p.Glu126fs)	GPD1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1059755	NM_015141.4(GPD1L):c.232A>G (p.Met78Val)	GPD1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14433	NM_000238.4(KCNH2):c.2350C>T (p.Arg784Trp)	KCNH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1400429	NM_004982.4(KCNJ8):c.332A>G (p.Glu111Gly)	KCNJ8-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002406	NM_006514.4(SCN10A):c.3178T>G (p.Ser1060Ala)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027260	NM_006514.4(SCN10A):c.2852T>A (p.Leu951His)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034930	NM_006514.4(SCN10A):c.3394A>C (p.Lys1132Gln)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042304	NM_006514.4(SCN10A):c.2965G>A (p.Ala989Thr)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1062762	NM_006514.4(SCN10A):c.3214C>T (p.Gln1072Ter)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1306032	NM_006514.4(SCN10A):c.3425G>A (p.Arg1142His)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1307778	NM_006514.4(SCN10A):c.3156A>G (p.Thr1052=)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1307856	NM_006514.4(SCN10A):c.3108C>T (p.Val1036=)	LOC110121288	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 167 · Orphanet: 168 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
SCN10A	SCN10A	GWAS, GenCC, Orphanet
SCN5A	SCN5A	GWAS, GenCC, Orphanet
GATA4	GATA4	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SCN5A	Definitive	Autosomal dominant	Brugada syndrome 1	23
KCNH2	Moderate	Autosomal dominant	Brugada syndrome	8
CACNA1C	Supportive	Autosomal dominant	Brugada syndrome	13
SCN2B	Supportive	Autosomal dominant	Brugada syndrome	7
SCNN1A	Supportive	Autosomal dominant	Brugada syndrome	12
SEMA3A	Supportive	Autosomal dominant	Brugada syndrome	7
SLMAP	Supportive	Autosomal dominant	Brugada syndrome	3
ABCC9	Limited	Autosomal dominant	Brugada syndrome	18
ANK2	Limited	Autosomal dominant	Brugada syndrome	11
CACNA2D1	Limited	Unknown	Brugada syndrome	8
CAV3	Limited	Autosomal dominant	Brugada syndrome	7
DEPDC5	Limited	Autosomal dominant	Brugada syndrome	11
DLG1	Limited	Unknown	Brugada syndrome	2
DLGAP5	Limited	Unknown	Brugada syndrome	2
KCNE5	Limited	Unknown	Brugada syndrome	4
KCNJ8	Limited	Unknown	Brugada syndrome	5
PKP2	Limited	Autosomal dominant	Brugada syndrome	6
RANGRF	Limited	Autosomal dominant	Brugada syndrome	2
RRAD	Limited	Autosomal dominant	Brugada syndrome
SCN10A	Limited	Unknown	Brugada syndrome	6
TRPM4	Limited	Autosomal dominant	Brugada syndrome	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN10A	Orphanet:101016	Romano-Ward syndrome
SCN10A	Orphanet:130	Brugada syndrome
SCN10A	Orphanet:306577	Hereditary sodium channelopathy-related small fibers neuropathy
SCN10A	Orphanet:46348	Paroxysmal extreme pain disorder
SCN10A	Orphanet:88642	Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN10A	Orphanet:90026	Primary erythromelalgia
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
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
CACNA2D1	Orphanet:130	Brugada syndrome
CACNA2D1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CACNA2D1	Orphanet:51083	Congenital short QT syndrome
SLMAP	Orphanet:130	Brugada syndrome
TRPM4	Orphanet:130	Brugada syndrome
TRPM4	Orphanet:316	Progressive symmetric erythrokeratodermia
TRPM4	Orphanet:871	Hereditary progressive cardiac conduction defect
GATA4	Orphanet:251071	8p23.1 microdeletion syndrome
GATA4	Orphanet:251510	46,XY partial gonadal dysgenesis
GATA4	Orphanet:3303	Tetralogy of Fallot
GATA4	Orphanet:334	Hereditary atrial fibrillation
GATA4	Orphanet:576232	Partial atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
GATA4	Orphanet:99103	Atrial septal defect, ostium secundum type
ANK2	Orphanet:101016	Romano-Ward syndrome
ABCC9	Orphanet:130	Brugada syndrome
ABCC9	Orphanet:1517	Cantú syndrome
ABCC9	Orphanet:154	Familial isolated dilated cardiomyopathy
ABCC9	Orphanet:334	Hereditary atrial fibrillation
KCNE5	Orphanet:130	Brugada syndrome
KCNE5	Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
KCNH2	Orphanet:101016	Romano-Ward syndrome
KCNH2	Orphanet:51083	Congenital short QT syndrome
KCNJ8	Orphanet:130	Brugada syndrome
KCNJ8	Orphanet:1517	Cantú syndrome
PKP2	Orphanet:130	Brugada syndrome
PKP2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
PKP2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
PKP2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant

Cohort genes → proteins

66 cohort genes, 63 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	13
gwas_and_clinvar	1
multi_evidence	52

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN10A	HGNC:10582	ENSG00000185313	Q9Y5Y9	Sodium channel protein type 10 subunit alpha	gwas,gencc,clinvar
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	gwas,gencc,clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	gencc,clinvar
CACNA2D1	HGNC:1399	ENSG00000153956	P54289	Voltage-dependent calcium channel subunit alpha-2/delta-1	gencc,clinvar
SLMAP	HGNC:16643	ENSG00000163681	Q14BN4	Sarcolemmal membrane-associated protein	gencc,clinvar
TRPM4	HGNC:17993	ENSG00000130529	Q8TD43	Transient receptor potential cation channel subfamily M member 4	gencc,clinvar
GATA4	HGNC:4173	ENSG00000136574	P43694	Transcription factor GATA-4	gwas,clinvar
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	gencc,clinvar
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	gencc,clinvar
KCNE5	HGNC:6241	ENSG00000176076	Q9UJ90	Potassium voltage-gated channel subfamily E regulatory beta subunit 5	gencc,clinvar
KCNH2	HGNC:6251	ENSG00000055118	Q12809	Voltage-gated inwardly rectifying potassium channel KCNH2	gencc,clinvar
KCNJ8	HGNC:6269	ENSG00000121361	Q15842	ATP-sensitive inward rectifier potassium channel 8	gencc,clinvar
PKP2	HGNC:9024	ENSG00000057294	Q99959	Plakophilin-2	gencc,clinvar
RRAD	HGNC:10446	ENSG00000166592	P55042	GTP-binding protein RAD	gencc
SCN2B	HGNC:10589	ENSG00000149575	O60939	Sodium channel regulatory subunit beta-2	gencc
SCNN1A	HGNC:10599	ENSG00000111319	P37088	Epithelial sodium channel subunit alpha	gencc
SEMA3A	HGNC:10723	ENSG00000075213	Q14563	Semaphorin-3A	gencc
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	gencc
DLGAP5	HGNC:16864	ENSG00000126787	Q15398	Disks large-associated protein 5	gencc
RANGRF	HGNC:17679	ENSG00000108961	Q9HD47	Ran guanine nucleotide release factor	gencc
DEPDC5	HGNC:18423	ENSG00000100150	O75140	GATOR1 complex protein DEPDC5	gencc
DLG1	HGNC:2900	ENSG00000075711	Q12959	Disks large homolog 1	gencc
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	clinvar
SCN1B	HGNC:10586	ENSG00000105711	Q07699	Sodium channel regulatory subunit beta-1	clinvar
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	clinvar
TBX20	HGNC:11598	ENSG00000164532	Q9UMR3	T-box transcription factor TBX20	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	clinvar
TGFB3	HGNC:11769	ENSG00000119699	P10600	Transforming growth factor beta-3 proprotein	clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
TTR	HGNC:12405	ENSG00000118271	P02766	Transthyretin	clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gwas
CACNB2	HGNC:1402	ENSG00000165995	Q08289	Voltage-dependent L-type calcium channel subunit beta-2	clinvar
IRX3	HGNC:14360	ENSG00000177508	P78415	Iroquois-class homeodomain protein IRX-3	gwas
IRX5	HGNC:14361	ENSG00000176842	P78411	Iroquois-class homeodomain protein IRX-5	gwas
ANKRD1	HGNC:15819	ENSG00000148677	Q15327	Ankyrin repeat domain-containing protein 1	clinvar
ZFPM2	HGNC:16700	ENSG00000169946	Q8WW38	Zinc finger protein ZFPM2	gwas
HCN4	HGNC:16882	ENSG00000138622	Q9Y3Q4	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	clinvar
CTDSPL	HGNC:16890	ENSG00000144677	O15194	CTD small phosphatase-like protein	clinvar
ACVR2B	HGNC:174	ENSG00000114739	Q13705	Activin receptor type-2B	clinvar
MYO18B	HGNC:18150	ENSG00000133454	Q8IUG5	Unconventional myosin-XVIIIb	gwas
SCN3B	HGNC:20665	ENSG00000166257	Q9NY72	Sodium channel regulatory subunit beta-3	clinvar
HDDC2	HGNC:21078	ENSG00000111906	Q7Z4H3	5’-deoxynucleotidase HDDC2	gwas
NCOA7	HGNC:21081	ENSG00000111912	Q8NI08	Nuclear receptor coactivator 7	gwas
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar
GPD1L	HGNC:28956	ENSG00000152642	Q8N335	Glycerol-3-phosphate dehydrogenase 1-like protein	clinvar
DMD	HGNC:2928	ENSG00000198947	P11532	Dystrophin	clinvar
MYBPHL	HGNC:30434	ENSG00000221986	A2RUH7	Myosin-binding protein H-like	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN10A	Sodium channel protein type 10 subunit alpha	Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes.
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.
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.
CACNA2D1	Voltage-dependent calcium channel subunit alpha-2/delta-1	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
SLMAP	Sarcolemmal membrane-associated protein	Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex.
TRPM4	Transient receptor potential cation channel subfamily M member 4	Calcium-activated selective cation channel that mediates membrane depolarization.
GATA4	Transcription factor GATA-4	Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function.
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).
KCNE5	Potassium voltage-gated channel subfamily E regulatory beta subunit 5	Potassium channel ancillary subunit that is essential for generation of some native K(+) currents by virtue of formation of heteromeric ion channel complex with voltage-gated potassium (Kv) channel pore-forming alpha subunits.
KCNH2	Voltage-gated inwardly rectifying potassium channel KCNH2	Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.
KCNJ8	ATP-sensitive inward rectifier potassium channel 8	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
PKP2	Plakophilin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
RRAD	GTP-binding protein RAD	May regulate basal voltage-dependent L-type Ca(2+) currents and be required for beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force.
SCN2B	Sodium channel regulatory subunit beta-2	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
SCNN1A	Epithelial sodium channel subunit alpha	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SEMA3A	Semaphorin-3A	Involved in the development of the olfactory system and in neuronal control of puberty.
CAV3	Caveolin-3	May act as a scaffolding protein within caveolar membranes.
DLGAP5	Disks large-associated protein 5	Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells.
RANGRF	Ran guanine nucleotide release factor	May regulate the intracellular trafficking of RAN.
DEPDC5	GATOR1 complex protein DEPDC5	As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway.
DLG1	Disks large homolog 1	Essential multidomain scaffolding protein required for normal development.
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.
SCN1B	Sodium channel regulatory subunit beta-1	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
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.
TGFB3	Transforming growth factor beta-3 proprotein	Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
TTR	Transthyretin	Thyroid hormone-binding protein.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
CACNB2	Voltage-dependent L-type calcium channel subunit beta-2	Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.
IRX3	Iroquois-class homeodomain protein IRX-3	Transcription factor involved in SHH-dependent neural patterning.
IRX5	Iroquois-class homeodomain protein IRX-5	Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene.
ANKRD1	Ankyrin repeat domain-containing protein 1	May play an important role in endothelial cell activation.
ZFPM2	Zinc finger protein ZFPM2	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.
HCN4	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation.
CTDSPL	CTD small phosphatase-like protein	Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.
ACVR2B	Activin receptor type-2B	Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c).
MYO18B	Unconventional myosin-XVIIIb	May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes.
SCN3B	Sodium channel regulatory subunit beta-3	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
HDDC2	5’-deoxynucleotidase HDDC2	Catalyzes the dephosphorylation of the nucleoside 5’-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).
NCOA7	Nuclear receptor coactivator 7	Enhances the transcriptional activities of several nuclear receptors.
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
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…
DMD	Dystrophin	Anchors the extracellular matrix to the cytoskeleton via F-actin.
MYBPHL	Myosin-binding protein H-like	Myosin-binding protein which plays a role in cardiac function.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 25 · Difficult: 17 · Unknown: 24 · Druggable fraction: 0.38

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	13	22.0×	2e-13
Antibody/Immunoglobulin	6	2.6×	0.101
Scaffold/PPI	7	1.8×	0.229
Kinase	4	1.7×	0.429
Transcription factor	10	1.2×	0.438
Phosphatase	1	1.3×	0.657
Transporter	1	1.2×	0.657
Other/Unknown	24	0.7×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN10A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNA2D1	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu
SLMAP	Other/Unknown	no		FHA_dom, SMAD_FHA_dom_sf, Cent_Immune-Sig_Mod
TRPM4	Ion channel	yes		Ion_trans_dom, TRPM_SLOG, TRPM
GATA4	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
KCNE5	Ion channel	yes		K_chnl_KCNE
KCNH2	Ion channel	yes		PAS, cNMP-bd_dom, PAS-assoc_C
KCNJ8	Ion channel	yes		K_chnl_inward-rec_Kir6.1, K_chnl_inward-rec_Kir_cyto, Ig_E-set
PKP2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
RRAD	Other/Unknown	no		Small_GTPase, Small_GTP-bd, RGK
SCN2B	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom
SCNN1A	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SEMA3A	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS
DLGAP5	Other/Unknown	no		SAPAP
RANGRF	Other/Unknown	no		Mog1, Mog1/PsbP_a/b/a-sand
DEPDC5	Other/Unknown	no		DEP_dom, IML1, WH-like_DNA-bd_sf
DLG1	Kinase	yes	2.7.4.8	SH3_domain, PDZ, L27_dom
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SCN1B	Antibody/Immunoglobulin	yes		Ig_V-set, Ig-like_fold, Na_channel_b1/b3
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
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
TGFB3	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
TTR	Other/Unknown	no		Transthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
CACNB2	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, VDCC_L_b2su
IRX3	Transcription factor	no		HD, Iroquois_homeo, KN_HD
IRX5	Transcription factor	no		HD, Iroquois_homeo, KN_HD
ANKRD1	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
ZFPM2	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
HCN4	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
CTDSPL	Phosphatase	yes		FCP1_dom, Dullard_phosphatase, HAD_sf
ACVR2B	Kinase	yes		TGFB_receptor, Activin_recp, Prot_kinase_dom
MYO18B	Other/Unknown	no		Myosin_head_motor_dom-like, P-loop_NTPase, MYSc_Myo18
SCN3B	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
HDDC2	Transcription factor	no		HD/PDEase_dom, HD_domain, YfbR/HDDC2
NCOA7	Other/Unknown	no		TLDc_dom, LysM, LysM_dom_sf
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
GPD1L	Other/Unknown	no		G3P_DH_NAD-dep_C, G3P_DH_NAD-dep, 6-PGluconate_DH-like_C_sf
DMD	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
MYBPHL	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin

Expression context

Cohort genes with no expression data: 0.

59 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)	66
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	11
right atrium auricular region	7
cardiac atrium	6
heart right ventricle	6
skeletal muscle tissue of rectus abdominis	5
hindlimb stylopod muscle	5
biceps brachii	4
skeletal muscle tissue of biceps brachii	4
left ventricle myocardium	4
cortical plate	4
heart left ventricle	3
cardiac muscle of right atrium	3
lateral nuclear group of thalamus	3
gastrocnemius	3
primordial germ cell in gonad	3
corpus callosum	3
jejunal mucosa	3
tendon of biceps brachii	3
bronchial epithelial cell	3
male germ line stem cell (sensu Vertebrata) in testis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN10A	21		marker	type B pancreatic cell, olfactory bulb, diaphragm
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CACNA2D1	261	ubiquitous	marker	biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis
SLMAP	260	ubiquitous	marker	saphenous vein, cauda epididymis, cardiac muscle of right atrium
TRPM4	201	ubiquitous	marker	mucosa of transverse colon, rectum, apex of heart
GATA4	85	broad	marker	right atrium auricular region, heart left ventricle, duodenum
ANK2	281	ubiquitous	marker	substantia nigra pars compacta, lateral nuclear group of thalamus, substantia nigra pars reticulata
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
KCNE5	117	broad	marker	primordial germ cell in gonad, substantia nigra, nucleus accumbens
KCNH2	211	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
KCNJ8	233	broad	marker	heart right ventricle, left ventricle myocardium, cardiac ventricle
PKP2	237	ubiquitous	marker	heart right ventricle, apex of heart, left ventricle myocardium
RRAD	234	ubiquitous	marker	olfactory segment of nasal mucosa, skeletal muscle tissue of rectus abdominis, heart right ventricle
SCN2B	182	broad	yes	middle temporal gyrus, lateral nuclear group of thalamus, cerebellar cortex
SCNN1A	283	broad	marker	nasal cavity epithelium, metanephros cortex, right uterine tube
SEMA3A	194	ubiquitous	marker	stromal cell of endometrium, cortical plate, colonic epithelium
CAV3	157	tissue_specific	yes	hindlimb stylopod muscle, vastus lateralis, triceps brachii
DLGAP5	186	ubiquitous	marker	secondary oocyte, ventricular zone, oocyte
RANGRF	274	ubiquitous	marker	left testis, right testis, testis
DEPDC5	236	ubiquitous	marker	paraflocculus, frontal pole, middle frontal gyrus
DLG1	294	ubiquitous	marker	endothelial cell, esophagus squamous epithelium, corpus callosum
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SCN1B	133	ubiquitous	marker	primary visual cortex, right hemisphere of cerebellum, cerebellum
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
SOS1	289	ubiquitous	marker	colonic epithelium, jejunal mucosa, tendon of biceps brachii
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
TGFB3	244	broad	marker	saphenous vein, endocervix, gall bladder

Protein interactions among cohort

Intra-cohort edges: 140.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK2	6,423
GATA4	4,994
DLG1	4,800
PRKCA	4,530
TTR	4,528
TTN	4,237
WT1	3,938
SOS1	3,625
AKAP9	3,537
KCNQ1	3,235

Intra-cohort edges

A	B	Sources
ABCC9	KCNE5	string_interaction
ABCC9	KCNJ8	string_interaction
ABCC9	MYBPC3	string_interaction
ABCC9	SCN5A	string_interaction
ABCC9	TCAP	string_interaction
AKAP9	KCNE3	string_interaction
AKAP9	KCNH2	string_interaction
AKAP9	KCNQ1	biogrid_interaction, intact, string_interaction
AKAP9	SNTA1	string_interaction
ANK2	CACNA2D1	intact
ANK2	DMD	intact
ANK2	TTN	string_interaction
ANKRD1	TCAP	string_interaction
ANKRD1	TTN	biogrid_interaction, string_interaction
CACNA1C	CACNA2D1	intact, string_interaction
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	CAV3	string_interaction
CACNA1C	GPD1L	string_interaction
CACNA1C	HCN4	string_interaction
CACNA1C	KCND3	string_interaction
CACNA1C	KCNH2	string_interaction
CACNA1C	KCNJ8	string_interaction
CACNA1C	RYR2	biogrid_interaction, string_interaction
CACNA1C	SCN3B	string_interaction
CACNA2D1	CACNB2	string_interaction
CACNA2D1	KCNJ8	string_interaction
CACNA2D1	RANGRF	string_interaction
CACNA2D1	SCN5A	string_interaction
CACNB2	GPD1L	string_interaction
CACNB2	HCN4	string_interaction
CACNB2	IRX5	string_interaction
CACNB2	KCNE3	string_interaction
CACNB2	KCNH2	string_interaction
CACNB2	KCNJ8	string_interaction
CACNB2	SCN1B	string_interaction
CACNB2	SCN3B	string_interaction
CACNB2	SCN5A	string_interaction
CAV3	DLG1	string_interaction
CAV3	DMD	string_interaction
CAV3	GPD1L	string_interaction
CAV3	SCN5A	string_interaction
CAV3	SNTA1	string_interaction
CTDSPL	KCNE3	intact
DLG1	KCNJ2	intact
DLG1	SCN5A	intact, string_interaction
DMD	SNTA1	biogrid_interaction, intact, string_interaction
DSP	PKP2	string_interaction
GATA4	HEY2	string_interaction
GATA4	MYH6	string_interaction
GATA4	TBX20	string_interaction

Structural data

PDB: 44 · AlphaFold-only: 19 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTR	P02766	462
SOS1	Q07889	91
TTN	Q8WZ42	64
SCN1B	Q07699	39
SCN2B	O60939	35
CACNA1C	Q13936	33
CACNA2D1	P54289	30
TRPM4	Q8TD43	29
WT1	P19544	28
KCNQ1	P51787	28
RYR2	Q92736	26
KCNH2	Q12809	24
MYBPC3	Q14896	17
SCN5A	Q14524	16
DLG1	Q12959	13
ANK2	Q01484	11
DEPDC5	O75140	11
TGFB3	P10600	11
ACVR2B	Q13705	9
SCN10A	Q9Y5Y9	8
HCN4	Q9Y3Q4	8
DMD	P11532	6
KCND3	Q9UK17	6
PRKCA	P17252	6
RRAD	P55042	5
DLGAP5	Q15398	4
TBX5	Q99593	4
HDDC2	Q7Z4H3	4
DSP	P15924	4
KCNE3	Q9Y6H6	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CAV3	P56539	88.54
MYBPHL	A2RUH7	86.64
SEMA3A	Q14563	84.50
KCNJ8	Q15842	84.00
ANKRD1	Q15327	82.64
ABCC9	O60706	81.72
SNTA1	Q13424	80.00
MAPRE2	Q15555	75.12
MYH6	P13533	74.91
LAMA4	Q16363	73.75
TBX20	Q9UMR3	67.87
HEY2	Q9UBP5	65.56
KCNE5	Q9UJ90	64.43
MYO18B	Q8IUG5	60.66
IRX5	P78411	55.14
IRX3	P78415	54.98
ZFPM2	Q8WW38	51.93
HRC	P23327	50.20
AKAP9	Q99996

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 331. Enrichment computed across 66 evidence-associated genes (54 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 54 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Muscle contraction	22	31.4×	1e-25	SCN10A, SCN5A, CACNA1C, ABCC9, KCNE5, KCNH2, RYR2, SCN1B (+14 more)
Cardiac conduction	18	36.2×	6e-22	SCN10A, SCN5A, CACNA1C, ABCC9, KCNE5, KCNH2, RYR2, SCN1B (+10 more)
Phase 0 - rapid depolarisation	8	51.3×	2e-10	SCN10A, SCN5A, CACNA1C, SCN1B, SCN2B, CACNB2, RANGRF, SCN3B
Phase 2 - plateau phase	6	84.6×	3e-09	CACNA1C, KCNE5, CACNB2, AKAP9, KCNE3, KCNQ1
Phase 3 - rapid repolarisation	5	105.7×	3e-08	KCNE5, KCNH2, AKAP9, KCNE3, KCNQ1
Interaction between L1 and Ankyrins	6	40.9×	3e-07	SCN10A, SCN5A, ANK2, SCN1B, SCN2B, SCN3B
Axon guidance	11	9.2×	1e-06	SCN10A, SCN5A, CACNA1C, ANK2, SCN1B, SCN2B, SEMA3A, SOS1 (+3 more)
Nervous system development	11	8.8×	1e-06	SCN10A, SCN5A, CACNA1C, ANK2, SCN1B, SCN2B, SEMA3A, SOS1 (+3 more)
Striated Muscle Contraction	5	28.6×	3e-05	TCAP, TTN, DMD, MYBPC3, MYH6
Non-integrin membrane-ECM interactions	6	17.1×	4e-05	SNTA1, TTR, COL5A1, DMD, LAMA4, PRKCA
Potassium Channels	6	14.9×	8e-05	ABCC9, KCNH2, KCNJ8, KCND3, KCNJ2, KCNQ1
L1CAM interactions	6	13.4×	1e-04	SCN10A, SCN5A, ANK2, SCN1B, SCN2B, SCN3B
Cardiogenesis	4	31.3×	2e-04	GATA4, TBX20, TBX5, HEY2
Developmental Biology	14	3.8×	3e-04	SCN10A, SCN5A, CACNA1C, ANK2, SCN1B, SCN2B, SEMA3A, SOS1 (+6 more)
Sensory perception of taste	4	24.9×	4e-04	SCN1B, SCN2B, SCNN1A, KCNJ2
Sensory Perception	6	10.6×	4e-04	SCN1B, SCN2B, SCNN1A, CACNB2, KCNJ2, PRKCA
Neuronal System	8	6.6×	5e-04	ABCC9, KCNH2, KCNJ8, CACNB2, KCND3, KCNJ2, KCNQ1, PRKCA
Inwardly rectifying K+ channels	3	39.6×	9e-04	ABCC9, KCNJ8, KCNJ2
Transcriptional regulation of testis differentiation	3	39.6×	9e-04	GATA4, WT1, ZFPM2
ATP sensitive Potassium channels	2	105.7×	0.002	ABCC9, KCNJ8
Formation of the dystrophin-glycoprotein complex (DGC)	3	17.1×	0.011	SNTA1, DMD, LAMA4
EGFR Transactivation by Gastrin	2	42.3×	0.014	SOS1, PRKCA
Sensory perception of sweet, bitter, and umami (glutamate) taste	3	15.5×	0.014	TRPM4, SCN1B, SCN2B
NCAM signaling for neurite out-growth	3	15.1×	0.014	CACNA1C, SOS1, CACNB2
NCAM1 interactions	3	13.8×	0.017	CACNA1C, CACNB2, COL5A1
Voltage gated Potassium channels	3	13.5×	0.018	KCNH2, KCND3, KCNQ1
Gastrin-CREB signalling pathway via PKC and MAPK	2	32.5×	0.020	SOS1, PRKCA
Developmental Lineage of Pancreatic Ductal Cells	3	12.7×	0.020	GATA4, COL5A1, LAMA4
Regulation of insulin secretion	3	12.2×	0.021	CACNA1C, CACNB2, PRKCA
YAP1- and WWTR1 (TAZ)-stimulated gene expression	2	28.2×	0.024	GATA4, TBX5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 63 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart rate by cardiac conduction	19	112.9×	7e-33	SCN5A, CACNA1C, CACNA2D1, TRPM4, ANK2, KCNE5, KCNH2, PKP2 (+11 more)
ventricular cardiac muscle cell action potential	12	188.8×	6e-24	SCN5A, ANK2, KCNE5, KCNH2, PKP2, RYR2, SNTA1, CAV3 (+4 more)
regulation of heart rate	14	104.0×	2e-23	SCN10A, SCN5A, ANK2, KCNJ8, RYR2, SNTA1, IRX5, CAV3 (+6 more)
regulation of ventricular cardiac muscle cell membrane repolarization	11	147.1×	3e-20	SCN5A, CACNA2D1, ANK2, KCNE5, KCNH2, SCN1B, SNTA1, CAV3 (+3 more)
cardiac muscle contraction	13	82.8×	3e-20	SCN5A, KCNE5, KCNH2, RYR2, SCN1B, SCN2B, TCAP, TTN (+5 more)
cardiac muscle cell action potential involved in contraction	9	100.3×	1e-14	SCN10A, SCN5A, CACNA1C, CACNA2D1, PKP2, SCN1B, SCN2B, SCN3B (+1 more)
regulation of sodium ion transmembrane transport	8	133.8×	3e-14	SCN5A, SLMAP, SCN1B, SNTA1, CAV3, RANGRF, DLG1, DMD
membrane repolarization during ventricular cardiac muscle cell action potential	7	187.2×	9e-14	KCNE5, KCNH2, KCNJ8, DLG1, KCND3, KCNE3, KCNQ1
membrane depolarization during cardiac muscle cell action potential	7	156.0×	5e-13	SCN5A, CACNA1C, SCN1B, SCN2B, HCN4, SCN3B, KCNJ2
regulation of atrial cardiac muscle cell membrane depolarization	6	178.3×	1e-11	SCN10A, SCN5A, SCN1B, SCN2B, TBX5, SCN3B
membrane depolarization during action potential	6	160.5×	3e-11	SCN10A, SCN5A, KCNH2, SCN1B, SCN2B, SCN3B
regulation of ventricular cardiac muscle cell action potential	6	133.8×	1e-10	CACNA1C, TRPM4, PKP2, RYR2, DLG1, DSP
positive regulation of sodium ion transport	6	80.2×	5e-09	SCN5A, PKP2, SCN1B, SCN2B, SCN3B, GPD1L
membrane repolarization during action potential	5	133.8×	8e-09	KCNE5, KCNH2, KCNE3, KCNJ2, KCNQ1
atrial cardiac muscle cell action potential	5	133.8×	8e-09	SCN5A, ANK2, KCNE5, SCN3B, KCNQ1
positive regulation of heart rate	6	66.9×	1e-08	TRPM4, RYR2, SCN3B, HEY2, HRC, KCNQ1
muscle contraction	8	26.4×	3e-08	SLMAP, SNTA1, TBX20, TTN, HCN4, HRC, KCND3, MYH6
regulation of membrane repolarization	5	102.9×	3e-08	KCNE5, KCNH2, AKAP9, KCNJ2, KCNQ1
membrane depolarization during AV node cell action potential	4	214.0×	4e-08	SCN5A, CACNA1C, TRPM4, CACNB2
regulation of cardiac muscle cell contraction	5	89.2×	7e-08	SCN5A, GATA4, ANK2, KCNJ2, MYBPC3
regulation of ventricular cardiac muscle cell membrane depolarization	4	178.3×	9e-08	SCN5A, CAV3, SCN3B, GPD1L
SA node cell action potential	4	178.3×	9e-08	SCN5A, ANK2, HCN4, SCN3B
potassium ion export across plasma membrane	5	83.6×	9e-08	KCNE5, KCNH2, KCND3, KCNE3, KCNQ1
regulation of cardiac muscle contraction	5	70.4×	2e-07	SCN10A, ANK2, RYR2, CAV3, HCN4
potassium ion import across plasma membrane	6	34.9×	6e-07	ABCC9, KCNH2, KCNJ8, HCN4, KCNJ2, KCNQ1
regulation of cardiac muscle cell action potential involved in regulation of contraction	4	118.9×	7e-07	CAV3, HCN4, RANGRF, AKAP9
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	5	53.5×	9e-07	CACNA1C, ANK2, RYR2, DMD, HRC
cardiac muscle hypertrophy	4	107.0×	1e-06	RYR2, TCAP, TTN, CAV3
cardiac conduction	4	107.0×	1e-06	CACNA1C, ABCC9, SCN1B, SCN2B
membrane repolarization during cardiac muscle cell action potential	4	107.0×	1e-06	KCNH2, KCND3, KCNJ2, KCNQ1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Hydroquinidine	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 15 · Phased (≥1): 19 · Undrugged: 47

Druggability breadth: 32 of 66 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
SCN10A	IMIPRAMINE
SCN5A	BEPRIDIL
CACNA1C	REMIFENTANIL
CACNA2D1	PREGABALIN
ABCC9	PINACIDIL ANHYDROUS
KCNH2	CETIRIZINE
SCNN1A	AMILORIDE
SOS1	IDARUBICIN
TTR	TRICLABENDAZOLE
CACNB2	NIMODIPINE
HCN4	IVABRADINE
ACVR2B	AXITINIB
KCND3	DULOXETINE
KCNQ1	AMBRISENTAN
PRKCA	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNH2	706	4
SCN5A	108	4
CACNA1C	85	4
PRKCA	39	4
TTR	29	4
SCN10A	21	4
KCNQ1	15	4
ACVR2B	12	4
KCND3	10	4
CACNA2D1	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN10A, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, SCN10A, SCN5A
NIFEDIPINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
DILTIAZEM	4	CACNA1C, KCNH2, SCN10A, SCN5A
MIBEFRADIL	4	CACNA1C, KCNH2, SCN10A, SCN5A
HALOPERIDOL	4	CACNA1C, KCNH2, SCN10A, SCN5A
MEXILETINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
AMITRIPTYLINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
AMIODARONE	4	CACNA1C, KCNH2, SCN10A, SCN5A
CHLORPROMAZINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
LAMOTRIGINE	4	SCN10A, SCN5A
BEPRIDIL	4	CACNA1C, KCNH2, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	CACNA1C, KCND3, KCNH2, KCNQ1, SCN5A
PALONOSETRON	4	KCNH2, KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
FEDRATINIB	4	KCNH2, SCN5A
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCND3, KCNH2, KCNQ1, SCN5A
DARIFENACIN	4	KCND3, KCNH2, KCNQ1, 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
PRKCA	1,148	Binding:1131, Functional:15, ADMET:2
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
TTR	423	Binding:391, Functional:32
SOS1	421	Binding:409, Functional:12
KCNQ1	179	Binding:96, Functional:64, ADMET:14, Toxicity:5
SCN10A	144	Binding:124, Functional:16, ADMET:4
KCND3	118	Binding:55, Functional:44, ADMET:12, Toxicity:7
ACVR2B	104	Binding:104
ABCC9	61	Functional:46, Binding:15
CACNA2D1	47	Binding:45, ADMET:1, Toxicity:1
KCNJ8	43	Functional:38, Binding:5
KCNJ2	31	Binding:23, ADMET:8
HCN4	30	Binding:20, ADMET:5, Functional:4, Toxicity:1
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
RYR2	15	Binding:15
SCN1B	15	Binding:7, ADMET:6, Toxicity:2
TRPM4	14	Binding:13, Functional:1
SCN2B	9	ADMET:4, Binding:3, Toxicity:2
SCNN1A	6	Binding:4, ADMET:1, Functional:1
GATA4	5	Binding:5
DSP	2	Binding:2
TBX5	1	Binding:1
TGFB3	1	Binding:1
TTN	1	Binding:1
MAPRE2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DLG1	2.7.4.8	guanylate kinase
TTN	2.7.11.1	non-specific serine/threonine protein kinase
PRKCA	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN10A	144
SCN5A	594
CACNA1C	575
KCNH2	4,851
SOS1	421
TTR	423
ACVR2B	104
KCND3	118
KCNQ1	179
PRKCA	1,148

Pharmacogenomics

Cohort genes with a PharmGKB record: 64; 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)
IMIPRAMINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
SERTINDOLE	4	CACNA1C, KCNH2, SCN10A, SCN5A
PIMOZIDE	4	CACNA1C, KCNH2, SCN10A, SCN5A
NIFEDIPINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
DILTIAZEM	4	CACNA1C, KCNH2, SCN10A, SCN5A
MIBEFRADIL	4	CACNA1C, KCNH2, SCN10A, SCN5A
HALOPERIDOL	4	CACNA1C, KCNH2, SCN10A, SCN5A
MEXILETINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
AMITRIPTYLINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
AMIODARONE	4	CACNA1C, KCNH2, SCN10A, SCN5A
CHLORPROMAZINE	4	CACNA1C, KCNH2, SCN10A, SCN5A
LAMOTRIGINE	4	SCN10A, SCN5A
BEPRIDIL	4	CACNA1C, KCNH2, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	CACNA1C, KCNH2, SCN5A
DROPERIDOL	4	CACNA1C, KCNH2, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	CACNA1C, KCND3, KCNH2, KCNQ1, SCN5A
PALONOSETRON	4	KCNH2, KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
FEDRATINIB	4	KCNH2, SCN5A
QUINIDINE	4	CACNA1C, KCNH2, SCN5A
DARUNAVIR	4	KCND3, KCNH2, KCNQ1, SCN5A
DARIFENACIN	4	KCND3, KCNH2, KCNQ1, SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	SCN10A, SCN5A, CACNA1C, CACNA2D1, ABCC9, KCNH2, SCNN1A, SOS1, TTR, CACNB2 (+5 more)
B	Phased (≥1) drug, not yet approved	4	KCNJ8, SCN2B, RYR2, SCN1B
C	Druggable family + PDB, no drug	8	TRPM4, DLG1, TTN, CTDSPL, SCN3B, KCNE3, KCNJ2, MYBPC3
D	Druggable family + AlphaFold only, no drug	3	KCNE5, SEMA3A, MYBPHL
E	Difficult family or no structure, no drug	36	SLMAP, GATA4, ANK2, PKP2, RRAD, CAV3, DLGAP5, RANGRF, DEPDC5, SNTA1 (+26 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKP2	0	SCN5A
RANGRF	0	SCN5A
SNTA1	0	SCN5A
SCN3B	0	SCN2B, SCN5A
GPD1L	0	SCN5A, SCN1B, CACNB2
AKAP9	0	KCNQ1
KCNE3	0	KCNQ1, KCND3
SLMAP	0	—
TRPM4	14	—
GATA4	5	—
ANK2	0	—
KCNE5	0	—
RRAD	0	—
SEMA3A	0	—
CAV3	0	—
DLGAP5	0	—
DEPDC5	0	—
DLG1	0	—
TBX20	0	—
TBX5	1	—
TCAP	0	—
TGFB3	1	—
TTN	1	—
WT1	0	—
IRX3	0	—
IRX5	0	—
ANKRD1	0	—
ZFPM2	0	—
CTDSPL	0	—
MYO18B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 43.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	38
PHASE3	2
PHASE2	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT04257994	Not specified	RECRUITING	Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
NCT05283759	Not specified	RECRUITING	UZ Brussel HRMC Registry of Brugada Syndrome
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05643209	Not specified	RECRUITING	Brugada Syndrome Substrate Characterization and Ablation
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06647927	Not specified	RECRUITING	GenLab: Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis
NCT06888271	Not specified	NOT_YET_RECRUITING	DNA Methylation in Brugada Syndrome and Risk of Sudden Cardiac Death
NCT06988189	Not specified	RECRUITING	Unmasking Concealed Arrhythmia Syndromes
NCT07364656	Not specified	NOT_YET_RECRUITING	Analysis of the Presence and Cardiac Functional Effects of Anti-NaV1.5 Autoantibodies in Patients With Metastatic Tumors
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT02014961	Not specified	UNKNOWN	Worm Study: Modifier Genes in Sudden Cardiac Death
NCT02052765	Not specified	COMPLETED	AnalyST & Brugada Syndrome - Feasibility Study
NCT02302274	Not specified	COMPLETED	Diagnostic Value and Safety of Flecainide Infusion Test in Brugada Syndrome
NCT02344277	Not specified	COMPLETED	Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
NCT02641431	Not specified	COMPLETED	Epicardial Ablation in Brugada Syndrome
NCT02704416	Not specified	COMPLETED	Ablation in Brugada Syndrome for the Prevention of VF
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03435393	Not specified	UNKNOWN	Ripple Mapping for Epicardial Mapping of Brugada Syndrome
NCT03485508	Not specified	UNKNOWN	The Brugada Syndrome: a Follow-up Study
NCT03491475	Not specified	UNKNOWN	Echocardiography During Ajmaline Test
NCT03524079	Not specified	COMPLETED	Right Ventricle Morphology and Hemodynamics in BrS
NCT03764592	Not specified	COMPLETED	VF Mapping in Brugada and Early Repolarization Syndromes
NCT03992677	Not specified	COMPLETED	Feasibility of Improving Risk Stratification in Brugada Syndrome
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04232787	Not specified	UNKNOWN	Southeast Asian Brugada Syndrome Cohort
NCT04420078	Not specified	COMPLETED	Brugada Ablation of VF Substrate Ongoing MultiCenter Registry
NCT04580992	Not specified	UNKNOWN	Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04808193	Not specified	UNKNOWN	European Perioperative Brugada Survey
NCT05048602	Not specified	UNKNOWN	Drug-induced Brugada Syndrome Research Database
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05685134	Not specified	COMPLETED	Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLECAINIDE	4	3
EMPAGLIFLOZIN	4	1
PROCAINAMIDE	4	1
AJMALINE	3	6
HYDROQUINIDINE	3	1
CHEMBL2105617	0	6
CHEMBL4780668	0	6
CHEMBL1740727	0	1
CHEMBL454299	0	1
HYDROQUININE	-1	1

Cohort genes: SCN10A, SCN5A, CACNA1C, CACNA2D1, SLMAP, TRPM4, ANK2, ABCC9, KCNE5, KCNH2, KCNJ8, PKP2, GATA4, RRAD, SCN2B, SCNN1A, SEMA3A, CAV3, DLGAP5, RANGRF, DEPDC5, DLG1, RYR2, SCN1B, SNTA1, SOS1, TBX20, TBX5, TCAP, TGFB3, TTN, TTR, WT1, CACNB2, IRX3, IRX5, ANKRD1, ZFPM2, HCN4, CTDSPL, ACVR2B, MYO18B, SCN3B, HDDC2, NCOA7, COL5A1, GPD1L, DMD, MYBPHL, DSP, CRNDE, AKAP9, CACNA2D1-AS1, HEY2, HRC, KCNJ8-AS1, KCND3, KCNE3, KCNJ2, KCNQ1, LAMA4, MAPRE2, MYBPC3, MYH6, ACAA1, PRKCA
Drugs: Flecainide, Empagliflozin, Procainamide, Ajmaline, Hydroquinidine
Associated genes: FGF12, TMEM168