Atrial fibrillation

Summary

Atrial fibrillation (MONDO:0004981) is a disease with 75 cohort genes (3,124 GWAS associations across 86 studies) and 3,017 clinical trials. The dominant Reactome pathway is Cardiac conduction (14 cohort genes). Top therapeutic interventions include amiodarone, dabigatran etexilate, and flecainide.

At a glance

• Cohort genes: 75
• GWAS associations: 3,124
• ClinVar variants: 49
• Clinical trials: 3,017

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation
Mondo ID	MONDO:0004981
EFO	EFO:0000275
MeSH	D001281
DOID	DOID:0060224
ICD-11	171698302
NCIT	C50466
SNOMED CT	49436004
UMLS	C0004238
MedGen	445
Anatomy (UBERON)	UBERON:0002081
Is cancer (heuristic)	no

Also known as: AF · AFib · atrial fibrillation · atrial fibrillation (disease)

Data availability: 49 ClinVar variants · 3,124 GWAS associations (86 studies) · 6 GenCC gene-disease records · 1 HPO phenotype · 33 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › atrial fibrillation

Related subtypes (16): ventricular fibrillation, cardiac arrest, ventricular tachycardia, atrial tachycardia, torsade-de-pointes syndrome with short coupling interval, sinoatrial node dysfunction and deafness, sino-auricular heart block, multifocal atrial tachycardia, His bundle tachycardia, incessant infant ventricular tachycardia, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, sudden arrhythmia death syndrome, cardiac conduction defect, sudden cardiac arrest, cardiac conduction disease with or without cardiomyoopathy, cardiogenetic rhythm disorder

Subtypes (3): familial atrial fibrillation, persistent atrial fibrillation, paroxysmal atrial fibrillation

Genetics & variants

GWAS landscape

3,124 GWAS associations across 86 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
rs12644625	6e-306	LINC01438	T	0.5
rs17042098	6e-305	PITX2 - LINC01438	A	0.09
rs6843082	3e-155	LINC01438	G	1.45
rs247617	1e-149	HERPUD1 - CETP	?
rs67329386	1e-146	ZFHX3	T	0.18
rs185158502	3e-141	NEURL1	?	1.43
rs2129977	7e-136	LINC01438	A	1.45
rs2220427	2e-134	LINC01438	T	1.71
rs3853445	6e-113	LINC01438 - MIR297	T	1.22
rs6838973	7e-109	LINC01438 - MIR297	T	0.03
rs964184	2e-108	ZPR1	?
rs4540107	2e-101	LINC01438	A	0.5
rs2359171	3e-100	ZFHX3	A	1.21
rs61303432	7e-92	LINC01438	T	1.71
rs780094	4e-91	GCKR	?
rs2106261	1e-90	ZFHX3	T	0.04
rs11264280	1e-89	KCNN3 - PMVK	T	0.13
rs2595104	5e-88	PITX2	T	1.18
rs2595117	3e-81	PITX2 - LINC01438	C	0.03
rs74154539	9e-77	NEURL1	A	0.14
rs6817105	2e-74	LINC01438	C	1.64
rs1997571	1e-73	CAV1	A	0.11
rs112599895	7e-71	PITX2 - LINC01438	G	1.9
rs8082812	5e-67	THEMIS3P - AKR1B1P6	?
rs11598047	9e-66	NEURL1	G	1.17
rs680084	2e-63	GORAB - PRRX1	A	0.1
rs17042171	4e-63	LINC01438	A	1.65
rs883079	8e-60	TBX5	T	0.1
rs373205748	2e-58	NEURL1	?	1.48
rs11773845	5e-58	CAV1	A	1.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90204201	Miyazawa K	2023	77,690	1,167,040	Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction.
GCST006414	Nielsen JB	2018	60,620	970,216	Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.
GCST006061	Roselli C	2018	55,114	482,295	Multi-ethnic genome-wide association study for atrial fibrillation.
GCST90018796	Sakaue S	2021	29,212	400,539	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90080015	Backman JD	2021	20,107	366,749	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084001	Backman JD	2021	20,107	366,749	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90446419	Chen Y	2024	19,738	423,444	The performance of AlphaMissense to identify genes influencing disease.
GCST004295	Christophersen IE	2017	15,979	102,776	Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.
GCST004296	Christophersen IE	2017	15,979	102,776	Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.
GCST004297	Christophersen IE	2017	15,979	102,776	Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	16
non_coding_transcript_exon_variant	3
3_prime_UTR_variant	3
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2129977	4	110791276	A>G,T	0.26	intron_variant	LINC01438		Tier 4: intronic/intergenic
rs6843082	4	110796911	G>A,T	0.22	non_coding_transcript_exon_variant	LINC01438		Tier 4: intronic/intergenic
rs6847935	4	110775495	A>T	0.22	intergenic_variant	PITX2 - LINC01438		Tier 4: intronic/intergenic
rs75021220	4	110737238	C>A,T	0.12	intergenic_variant	PITX2 - LINC01438		Tier 4: intronic/intergenic
rs67249485	4	110778529	A>C,G,T	0.199	intergenic_variant	PITX2 - LINC01438		Tier 4: intronic/intergenic
rs17042175	4	110789811	T>A	0.209	intron_variant	LINC01438		Tier 4: intronic/intergenic
rs12644625	4	110795357	C>G,T	0.05	intron_variant	LINC01438	6e-306	Tier 4: intronic/intergenic
rs17042098	4	110743002	G>A,T	0.05	intergenic_variant	PITX2 - LINC01438	6e-305	Tier 4: intronic/intergenic
rs247617	16	56956804	C>A	0.05	intergenic_variant	HERPUD1 - CETP	1e-149	Tier 4: intronic/intergenic
rs67329386	16	73014468	C>T	0.221	non_coding_transcript_exon_variant	ZFHX3	1e-146	Tier 4: intronic/intergenic
rs185158502	10	103574950	A>G		intron_variant	NEURL1	3e-141	Tier 4: intronic/intergenic
rs2220427	4	110793733	C>A,G,T	0.45	intron_variant	LINC01438	2e-134	Tier 4: intronic/intergenic
rs3853445	4	110840331	T>C	0.26	regulatory_region_variant	LINC01438 - MIR297	6e-113	Tier 3: regulatory
rs6838973	4	110844339	C>G,T	0.05	intergenic_variant	LINC01438 - MIR297	7e-109	Tier 4: intronic/intergenic
rs964184	11	116778201	G>C	0.05	3_prime_UTR_variant	ZPR1	2e-108	Tier 2: splice/UTR
rs4540107	4	110789946	C>A,G,T	0.446	intron_variant	LINC01438	2e-101	Tier 4: intronic/intergenic
rs2359171	16	73019123	T>A	0.19	intron_variant	ZFHX3	3e-100	Tier 4: intronic/intergenic
rs61303432	4	110789386	C>G,T	0.14	intron_variant	LINC01438	7e-92	Tier 4: intronic/intergenic
rs780094	2	27518370	T>A,C,G	0.05	intron_variant	GCKR	4e-91	Tier 4: intronic/intergenic
rs2106261	16	73017721	C>A,G,T	0.05	intron_variant	ZFHX3	1e-90	Tier 4: intronic/intergenic
rs11264280	1	154890476	C>A,T	0.321	intergenic_variant	KCNN3 - PMVK	1e-89	Tier 4: intronic/intergenic
rs2595104	4	110631977	T>G	0.31	intron_variant	PITX2	5e-88	Tier 4: intronic/intergenic
rs2595117	4	110674360	C>A,G,T	0.05	intergenic_variant	PITX2 - LINC01438	3e-81	Tier 4: intronic/intergenic
rs74154539	10	103556539	G>A	0.178	intron_variant	NEURL1	9e-77	Tier 4: intronic/intergenic
rs6817105	4	110784612	T>A,C,G	0.13	intron_variant	LINC01438	2e-74	Tier 4: intronic/intergenic
rs1997571	7	116558567	G>A,C	0.406	intron_variant	CAV1	1e-73	Tier 4: intronic/intergenic
rs112599895	4	110735436	A>G	0.01	intergenic_variant	PITX2 - LINC01438	7e-71	Tier 4: intronic/intergenic
rs8082812	18	8522684	C>A	0.05	intergenic_variant	THEMIS3P - AKR1B1P6	5e-67	Tier 4: intronic/intergenic
rs11598047	10	103582915	A>G	0.162	non_coding_transcript_exon_variant	NEURL1	9e-66	Tier 4: intronic/intergenic
rs680084	1	170659114	G>A,T	0.477	intron_variant	GORAB - PRRX1	2e-63	Tier 4: intronic/intergenic

ClinVar germline variants

49 retrieved; paginated sample, class counts are floors:

15 conflicting classifications of pathogenicity, 14 uncertain significance, 8 benign/likely benign, 4 pathogenic, 3 likely pathogenic, 3 likely benign, 1 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
2504113	NM_006587.4(CORIN):c.684dup (p.Met229fs)	CORIN	Pathogenic	criteria provided, single submitter
3143	NM_000218.3(KCNQ1):c.418A>G (p.Ser140Gly)	KCNQ1	Pathogenic	no assertion criteria provided
67072	NM_000218.3(KCNQ1):c.421G>A (p.Val141Met)	KCNQ1	Pathogenic	criteria provided, multiple submitters, no conflicts
67094	NM_000218.3(KCNQ1):c.625T>C (p.Ser209Pro)	KCNQ1	Pathogenic	criteria provided, single submitter
3338330	NM_000218.3(KCNQ1):c.508G>A (p.Glu170Lys)	KCNQ1	Likely pathogenic	criteria provided, single submitter
3338339	NM_000335.5(SCN5A):c.1127G>T (p.Arg376Leu)	SCN5A	Likely pathogenic	criteria provided, single submitter
68002	NM_000335.5(SCN5A):c.5621T>C (p.Met1874Thr)	SCN5A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
6055	NM_172201.2(KCNE2):c.79C>T (p.Arg27Cys)	KCNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30121	NM_000891.3(KCNJ2):c.277G>A (p.Val93Ile)	KCNJ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
629754	NM_000218.3(KCNQ1):c.1109C>T (p.Ala370Val)	KCNQ1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
67087	NM_000218.3(KCNQ1):c.583C>T (p.Arg195Trp)	KCNQ1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
47051	NM_001267550.2(TTN):c.4359A>T (p.Arg1453Ser)	LOC101927055	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
46644	NM_001267550.2(TTN):c.18776C>G (p.Thr6259Ser)	LOC126806430	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
379225	NM_000335.5(SCN5A):c.4434+5G>A	SCN5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68014	NM_000335.5(SCN5A):c.5848G>A (p.Val1950Met)	SCN5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9402	NM_000335.5(SCN5A):c.5452G>A (p.Asp1818Asn)	SCN5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8476	NM_003098.3(SNTA1):c.1169C>T (p.Ala390Val)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137827	NM_001267550.2(TTN):c.8902+14T>A	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
47010	NM_001267550.2(TTN):c.47315G>A (p.Arg15772Gln)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
47633	NM_001267550.2(TTN):c.101212C>T (p.Arg33738Cys)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
47636	NM_001267550.2(TTN):c.9359G>A (p.Arg3120Gln)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
691748	NM_001267550.2(TTN):c.44014G>A (p.Asp14672Asn)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16998	NM_181703.4(GJA5):c.286G>T (p.Ala96Ser)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
404123	NM_005477.3(HCN4):c.2716G>A (p.Gly906Arg)	HCN4	Uncertain significance	criteria provided, multiple submitters, no conflicts
67074	NM_000218.3(KCNQ1):c.440A>G (p.Gln147Arg)	KCNQ1	Uncertain significance	criteria provided, single submitter
617741	NM_000257.4(MYH7):c.5190G>T (p.Met1730Ile)	LOC126861897	Uncertain significance	criteria provided, multiple submitters, no conflicts
30045	NM_000335.5(SCN5A):c.5958C>A (p.Asn1986Lys)	SCN5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
30046	NM_000335.5(SCN5A):c.1333C>G (p.His445Asp)	SCN5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
30047	NM_000335.5(SCN5A):c.1410C>G (p.Asn470Lys)	SCN5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
30048	NM_000335.5(SCN5A):c.1282G>A (p.Glu428Lys)	SCN5A	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 73 · Orphanet: 104 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 6

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

Gene	HGNC	Evidence routes
SCN5A	SCN5A	GWAS, Orphanet
TTN	TTN	GWAS, Orphanet
HCN4	HCN4	GWAS, Orphanet
GJA5	GJA5	GWAS, Orphanet
KCNH2	KCNH2	GWAS, Orphanet
KCNJ2	KCNJ2	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
LMNA	Moderate	Autosomal dominant	atrial fibrillation	40
KCNE1	Limited	Autosomal dominant	atrial fibrillation	7
KCNE5	Limited	X-linked	atrial fibrillation	4
MYBPC3	Limited	Autosomal dominant	atrial fibrillation	13
SHOX2	Limited	Autosomal dominant	atrial fibrillation	2
SOX4	Limited	Autosomal dominant	atrial fibrillation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
HCN4	Orphanet:130	Brugada syndrome
HCN4	Orphanet:166282	Hereditary sick sinus syndrome
GJA5	Orphanet:3303	Tetralogy of Fallot
GJA5	Orphanet:334	Hereditary atrial fibrillation
KCNH2	Orphanet:101016	Romano-Ward syndrome
KCNH2	Orphanet:51083	Congenital short QT syndrome
KCNJ2	Orphanet:334	Hereditary atrial fibrillation
KCNJ2	Orphanet:37553	Andersen-Tawil syndrome
KCNJ2	Orphanet:51083	Congenital short QT syndrome
SOX4	Orphanet:1465	Coffin-Siris syndrome
KCNE1	Orphanet:101016	Romano-Ward syndrome
KCNE1	Orphanet:334	Hereditary atrial fibrillation
KCNE1	Orphanet:90647	Jervell and Lange-Nielsen syndrome
KCNE5	Orphanet:130	Brugada syndrome
KCNE5	Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
LMNA	Orphanet:154	Familial isolated dilated cardiomyopathy
LMNA	Orphanet:157973	Congenital muscular dystrophy due to LMNA mutation
LMNA	Orphanet:1662	Restrictive dermopathy
LMNA	Orphanet:168796	Heart-hand syndrome, Slovenian type
LMNA	Orphanet:2229	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
LMNA	Orphanet:2348	Familial partial lipodystrophy, Dunnigan type
LMNA	Orphanet:280365	Autosomal semi-dominant severe lipodystrophic laminopathy
LMNA	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LMNA	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LMNA	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LMNA	Orphanet:300751	Familial dilated cardiomyopathy with conduction defect due to LMNA mutation
LMNA	Orphanet:363618	LMNA-related cardiocutaneous progeria syndrome
LMNA	Orphanet:54260	Left ventricular noncompaction
LMNA	Orphanet:675396	Epithelioid hemangioma

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	62
gwas_and_clinvar	6
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	gwas,clinvar
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	gwas,clinvar
HCN4	HGNC:16882	ENSG00000138622	Q9Y3Q4	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	gwas,clinvar
GJA5	HGNC:4279	ENSG00000265107	P36382	Gap junction alpha-5 protein	gwas,clinvar
KCNH2	HGNC:6251	ENSG00000055118	Q12809	Voltage-gated inwardly rectifying potassium channel KCNH2	gwas,clinvar
KCNJ2	HGNC:6263	ENSG00000123700	P63252	Inward rectifier potassium channel 2	gwas,clinvar
SHOX2	HGNC:10854	ENSG00000168779	O60902	Short stature homeobox protein 2	gencc
SOX4	HGNC:11200	ENSG00000124766	Q06945	Transcription factor SOX-4	gencc
KCNE1	HGNC:6240	ENSG00000180509	P15382	Potassium voltage-gated channel subfamily E member 1	gencc
KCNE5	HGNC:6241	ENSG00000176076	Q9UJ90	Potassium voltage-gated channel subfamily E regulatory beta subunit 5	gencc
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	gencc
MYBPC3	HGNC:7551	ENSG00000134571	Q14896	Myosin-binding protein C, cardiac-type	gencc
RNF11	HGNC:10056	ENSG00000123091	Q9Y3C5	RING finger protein 11	gwas
OPN1SW	HGNC:1012	ENSG00000128617	P03999	Short-wave-sensitive opsin 1	gwas
RPL3L	HGNC:10351	ENSG00000140986	Q92901	Ribosomal protein uL3-like	gwas
RPS2	HGNC:10404	ENSG00000140988	P15880	Small ribosomal subunit protein uS5	gwas
ATXN1	HGNC:10548	ENSG00000124788	P54253	Ataxin-1	gwas
SCN10A	HGNC:10582	ENSG00000185313	Q9Y5Y9	Sodium channel protein type 10 subunit alpha	gwas
BMP2	HGNC:1069	ENSG00000125845	P12643	Bone morphogenetic protein 2	gwas
SGCG	HGNC:10809	ENSG00000102683	Q13326	Gamma-sarcoglycan	gwas
SLC1A4	HGNC:10942	ENSG00000115902	P43007	Neutral amino acid transporter A	gwas
SLC24A2	HGNC:10976	ENSG00000155886	Q9UI40	Sodium/potassium/calcium exchanger 2	gwas
SLC27A6	HGNC:11000	ENSG00000113396	Q9Y2P4	Long-chain fatty acid transport protein 6	gwas
SLIT1	HGNC:11085	ENSG00000187122	O75093	Slit homolog 1 protein	gwas
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	clinvar
SORL1	HGNC:11185	ENSG00000137642	Q92673	Sortilin-related receptor	gwas
SOX15	HGNC:11196	ENSG00000129194	O60248	Transcription factor SOX-15	gwas
SSPN	HGNC:11322	ENSG00000123096	Q14714	Sarcospan	gwas
STC2	HGNC:11374	ENSG00000113739	O76061	Stanniocalcin-2	gwas
SYK	HGNC:11491	ENSG00000165025	P43405	Tyrosine-protein kinase SYK	gwas
TBX3	HGNC:11602	ENSG00000135111	O15119	T-box transcription factor TBX3	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
THRB	HGNC:11799	ENSG00000151090	P10828	Thyroid hormone receptor beta	gwas
TLE3	HGNC:11839	ENSG00000140332	Q04726	Transducin-like enhancer protein 3	gwas
TNFSF12	HGNC:11927	ENSG00000239697	O43508	Tumor necrosis factor ligand superfamily member 12	gwas
MYOT	HGNC:12399	ENSG00000120729	Q9UBF9	Myotilin	gwas
TUBA8	HGNC:12410	ENSG00000183785	Q9NY65	Tubulin alpha-8 chain	gwas
UBE4B	HGNC:12500	ENSG00000130939	O95155	Ubiquitin conjugation factor E4 B	gwas
USP3	HGNC:12626	ENSG00000140455	Q9Y6I4	Ubiquitin carboxyl-terminal hydrolase 3	gwas
WIPF1	HGNC:12736	ENSG00000115935	O43516	WAS/WASL-interacting protein family member 1	gwas
WDR1	HGNC:12754	ENSG00000071127	O75083	WD repeat-containing protein 1	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
WNT8A	HGNC:12788	ENSG00000061492	Q9H1J5	Protein Wnt-8a	gwas
XPO1	HGNC:12825	ENSG00000082898	O14980	Exportin-1	gwas
YWHAE	HGNC:12851	ENSG00000108953	P62258	14-3-3 protein epsilon	gwas
RASSF8	HGNC:13232	ENSG00000123094	Q8NHQ8	Ras association domain-containing protein 8	gwas
FAM13B	HGNC:1335	ENSG00000031003	Q9NYF5	Protein FAM13B	gwas
SMIM29	HGNC:1340	ENSG00000186577	Q86T20	Small integral membrane protein 29	gwas
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	gwas
MYOZ1	HGNC:13752	ENSG00000177791	Q9NP98	Myozenin-1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
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.
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.
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.
SHOX2	Short stature homeobox protein 2	May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.
SOX4	Transcription factor SOX-4	Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5’-AACAAAG-3’ motif.
KCNE1	Potassium voltage-gated channel subfamily E member 1	Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.
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.
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.
RNF11	RING finger protein 11	Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways.
OPN1SW	Short-wave-sensitive opsin 1	Visual pigments are the light-absorbing molecules that mediate vision.
RPL3L	Ribosomal protein uL3-like	Heart- and skeletal muscle-specific component of the ribosome, which regulates muscle function.
RPS2	Small ribosomal subunit protein uS5	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
ATXN1	Ataxin-1	Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor.
SCN10A	Sodium channel protein type 10 subunit alpha	Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes.
BMP2	Bone morphogenetic protein 2	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis.
SGCG	Gamma-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
SLC1A4	Neutral amino acid transporter A	Sodium-coupled antiporter of neutral amino acids.
SLC24A2	Sodium/potassium/calcium exchanger 2	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
SLC27A6	Long-chain fatty acid transport protein 6	Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane.
SLIT1	Slit homolog 1 protein	Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors.
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
SORL1	Sortilin-related receptor	Sorting receptor that directs several proteins to their correct location within the cell.
SOX15	Transcription factor SOX-15	Transcription factor that binds to DNA at the 5’-AACAATG-3’ consensus sequence.
SSPN	Sarcospan	Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix.
STC2	Stanniocalcin-2	Has an anti-hypocalcemic action on calcium and phosphate homeostasis.
SYK	Tyrosine-protein kinase SYK	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR).
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
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.
THRB	Thyroid hormone receptor beta	Nuclear hormone receptor that can act as a repressor or activator of transcription.
TLE3	Transducin-like enhancer protein 3	Transcriptional coregulator that binds to a number of transcription factors.
TNFSF12	Tumor necrosis factor ligand superfamily member 12	Binds to FN14 and possibly also to TNRFSF12/APO3.
MYOT	Myotilin	Component of a complex of multiple actin cross-linking proteins.
TUBA8	Tubulin alpha-8 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
UBE4B	Ubiquitin conjugation factor E4 B	Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases.
USP3	Ubiquitin carboxyl-terminal hydrolase 3	Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity.
WIPF1	WAS/WASL-interacting protein family member 1	Plays a role in the reorganization of the actin cytoskeleton.
WDR1	WD repeat-containing protein 1	Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins.
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.
WNT8A	Protein Wnt-8a	Ligand for members of the frizzled family of seven transmembrane receptors.
XPO1	Exportin-1	Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs.
YWHAE	14-3-3 protein epsilon	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
MYOZ1	Myozenin-1	Myozenins may serve as intracellular binding proteins involved in linking Z-disk proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere.
DMRTA2	Doublesex- and mab-3-related transcription factor A2	May be involved in sexual development.
PRDM8	PR domain zinc finger protein 8	Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3.
XPO7	Exportin-7	Mediates the nuclear export of proteins (cargos) with broad substrate specificity.

Protein-family classification

Druggable: 18 · Difficult: 18 · Unknown: 39 · Druggable fraction: 0.24

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	7	10.4×	5e-05
Nuclear receptor	1	5.2×	0.590
Scaffold/PPI	7	1.6×	0.590
Transcription factor	11	1.2×	0.741
Antibody/Immunoglobulin	3	1.2×	0.852
Kinase	3	1.1×	0.852
Protease	2	1.0×	0.873
Other/Unknown	39	0.9×	0.980
GPCR	1	0.3×	0.999
Enzyme (other)	1	0.2×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
HCN4	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
GJA5	Other/Unknown	no		Connexin, Connexin40, Connexin_N
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
SHOX2	Transcription factor	no		HTH_motif, HD, OAR_dom
SOX4	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
KCNE1	Ion channel	yes		K_chnl_KCNE, KCNE1
KCNE5	Ion channel	yes		K_chnl_KCNE
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
MYBPC3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
RNF11	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, RNF11_RING-H2
OPN1SW	GPCR	yes		GPCR_Rhodpsn, Opsin_blue, Opsin
RPL3L	Other/Unknown	no		Ribosomal_uL3, Transl_B-barrel_sf, Ribosomal_uL3_CS
RPS2	Other/Unknown	no		Ribosomal_uS5, Ribosomal_uS5_C, Ribosomal_uS5_euk_arc
ATXN1	Other/Unknown	no		Ataxin_AXH_dom, Ataxin-1_N, Ataxin_AXH_dom_sf
SCN10A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
BMP2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SGCG	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
SLC1A4	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SLC24A2	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
SLC27A6	Other/Unknown	no		AMP-dep_synth/lig_dom, AMP-binding_CS, AMP-bd_C
SLIT1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, LRRNT, Cys-rich_flank_reg_C
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
SORL1	Antibody/Immunoglobulin	yes		LDLR_classB_rpt, LDrepeatLR_classA_rpt, FN3_dom
SOX15	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SRY-related_HMG-box_TF-like
SSPN	Other/Unknown	no		CD20-like_TM, Sarcospan
STC2	Other/Unknown	no		Stanniocalcin
SYK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TBX3	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
THRB	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
TLE3	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
TNFSF12	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
MYOT	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
TUBA8	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
UBE4B	Transcription factor	no	2.3.2.27	Ubox_domain, Znf_RING/FYVE/PHD, Ub_conjug_fac_E4_core
USP3	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD
WIPF1	Other/Unknown	no		WH2_dom, PH-like_dom_sf, WAS/WASL-interacting_domain
WDR1	Scaffold/PPI	no		WD40_rpt, N2O_reductase_N, WD40/YVTN_repeat-like_dom_sf
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
WNT8A	Other/Unknown	no		Wnt, Wnt8, Wnt_CS
XPO1	Other/Unknown	no		Importin-beta_N, ARM-like, Exportin-1/Importin-b-like
YWHAE	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
RASSF8	Other/Unknown	no		RA_dom, Ubiquitin-like_domsf, N-RASSF
FAM13B	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
SMIM29	Other/Unknown	no		SMIM29
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
MYOZ1	Other/Unknown	no		MYOZ

Expression context

Cohort genes with no expression data: 0.

68 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)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skeletal muscle tissue of rectus abdominis	7
apex of heart	6
cortical plate	6
hindlimb stylopod muscle	6
cardiac muscle of right atrium	6
ventricular zone	6
buccal mucosa cell	5
ganglionic eminence	5
blood	5
monocyte	5
gastrocnemius	5
calcaneal tendon	5
lateral nuclear group of thalamus	4
leukocyte	4
endothelial cell	4
stromal cell of endometrium	4
gluteal muscle	3
cardiac atrium	3
right atrium auricular region	3
tibialis anterior	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
HCN4	86	tissue_specific	yes	tibialis anterior, right atrium auricular region, cardiac atrium
GJA5	190	broad	marker	placenta, right coronary artery, left coronary artery
KCNH2	211	broad	marker	apex of heart, right atrium auricular region, cardiac atrium
KCNJ2	256	ubiquitous	marker	inferior vagus X ganglion, skeletal muscle tissue of rectus abdominis, dorsal motor nucleus of vagus nerve
SHOX2	167	broad	marker	buccal mucosa cell, lateral nuclear group of thalamus, saphenous vein
SOX4	295	ubiquitous	marker	cortical plate, ganglionic eminence, embryo
KCNE1	121	broad	marker	blood, monocyte, leukocyte
KCNE5	117	broad	marker	primordial germ cell in gonad, substantia nigra, nucleus accumbens
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen
MYBPC3	149	tissue_specific	marker	apex of heart, right atrium auricular region, cardiac atrium
RNF11	303	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, prefrontal cortex
OPN1SW	95	tissue_specific	yes	vena cava, sural nerve, Brodmann (1909) area 46
RPL3L	156	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, hindlimb stylopod muscle, vastus lateralis
RPS2	134	ubiquitous	marker	stromal cell of endometrium, right uterine tube, ovary
ATXN1	295	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, skeletal muscle tissue of rectus abdominis
SCN10A	21		marker	type B pancreatic cell, olfactory bulb, diaphragm
BMP2	238	broad	marker	cartilage tissue, pancreatic ductal cell, pigmented layer of retina
SGCG	184	broad	marker	skeletal muscle tissue of rectus abdominis, gluteal muscle, triceps brachii
SLC1A4	294	ubiquitous	marker	buccal mucosa cell, sperm, gluteal muscle
SLC24A2	110	broad	marker	endothelial cell, lateral nuclear group of thalamus, postcentral gyrus
SLC27A6	175	broad	marker	secondary oocyte, oocyte, right uterine tube
SLIT1	186	broad	marker	cortical plate, middle temporal gyrus, orbitofrontal cortex
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
SORL1	293	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
SOX15	229	broad	marker	lower esophagus mucosa, oocyte, esophagus mucosa
SSPN	285	ubiquitous	marker	synovial joint, skeletal muscle tissue of rectus abdominis, body of tongue
STC2	192	ubiquitous	marker	stromal cell of endometrium, tibia, epithelium of mammary gland
SYK	239	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 44.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SIRT1	8,285
XPO1	7,582
LMNA	7,173
RPS2	7,106
CAV1	6,673
SYK	5,172
RPL3L	4,559
ATXN1	4,465
TUBA8	4,465
TTN	4,237

Intra-cohort edges

A	B	Sources
AOPEP	SYNE2	string_interaction
ARNT2	THRB	string_interaction
CAMK2D	SCN5A	intact
CASQ2	KCNH2	string_interaction
CASQ2	SCN5A	string_interaction
CAV1	CAV2	biogrid_interaction, intact, string_interaction
CAV1	KCNH2	intact
CAV2	SCN10A	string_interaction
FAM13B	WNT8A	string_interaction
FAM13B	YWHAE	intact
GJA5	HCN4	string_interaction
GJA5	SCN5A	string_interaction
GJA5	SHOX2	string_interaction
GJA5	TBX3	string_interaction
GJA5	TBX5	string_interaction
HCN4	SCN5A	string_interaction
HCN4	SHOX2	string_interaction
HCN4	TBX3	string_interaction
KCNE1	KCNE5	string_interaction
KCNE1	KCNH2	biogrid_interaction, string_interaction
KCNE1	SCN5A	string_interaction
KCNE1	SNTA1	string_interaction
KCNH2	SCN5A	string_interaction
KCNH2	YWHAE	biogrid_interaction
LMNA	SYNE2	string_interaction
LMNA	TBX3	biogrid_interaction
MYBPC3	TTN	string_interaction
MYOCD	TBX5	string_interaction
MYOT	MYOZ1	string_interaction
MYOZ1	TTN	string_interaction
NEBL	TTN	string_interaction
OPN1SW	SLC24A2	string_interaction
RASSF8	YWHAE	intact
SCN10A	TBX5	string_interaction
SCN5A	SNTA1	biogrid_interaction, string_interaction
SGCG	SNTA1	string_interaction
SGCG	SSPN	string_interaction
SGCG	TTN	biogrid_interaction, intact
SHOX2	TBX3	string_interaction
SHOX2	TBX5	string_interaction
SLC1A4	SNTA1	intact
SNTA1	SSPN	string_interaction
TBX3	TBX5	string_interaction
XPO1	XPO7	string_interaction

Structural data

PDB: 41 · AlphaFold-only: 34 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS2	P15880	209
SYK	P43405	93
TTN	Q8WZ42	64
THRB	P10828	34
LMNA	P02545	28
KCNH2	Q12809	24
BMP2	P12643	21
XPO1	O14980	18
MYBPC3	Q14896	17
SCN5A	Q14524	16
ORMDL3	Q8N138	13
YWHAE	P62258	11
CAMK2D	Q13557	9
SIRT1	Q96EB6	9
HCN4	Q9Y3Q4	8
SCN10A	Q9Y5Y9	8
ATXN1	P54253	7
SORL1	Q92673	7
KCNE1	P15382	5
STC2	O76061	4
TBX5	Q99593	4
UBE4B	O95155	4
WIPF1	O43516	4
CASQ2	O14958	4
KCNJ2	P63252	3
MYOZ1	Q9NP98	3
SYNE2	Q8WXH0	3
MYOT	Q9UBF9	2
WDR1	O75083	2
OPN1SW	P03999	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPL3L	Q92901	94.79
TUBA8	Q9NY65	91.24
SLC27A6	Q9Y2P4	90.97
SNX6	Q9UNH7	89.14
XPO7	Q9UIA9	87.45
COG5	Q9UP83	84.37
KIFAP3	Q92845	83.66
AOPEP	Q8N6M6	83.36
SLIT1	O75093	80.28
SGCG	Q13326	80.24
FBXO32	Q969P5	80.15
SNTA1	Q13424	80.00
CALU	O43852	79.82
USP3	Q9Y6I4	79.40
RNF11	Q9Y3C5	78.98
CAV2	P51636	78.26
SSPN	Q14714	74.41
UACA	Q9BZF9	74.08
SMIM29	Q86T20	71.70
GJA5	P36382	70.35
SOX15	O60248	69.14
TLE3	Q04726	68.65
SLC24A2	Q9UI40	67.75
KCNE5	Q9UJ90	64.43
FAM13B	Q9NYF5	62.70
SHOX2	O60902	61.50
ARNT2	Q9HBZ2	59.49
CREB5	Q02930	57.95
DMRTA2	Q96SC8	57.64
MYOCD	Q8IZQ8	56.16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 807. Enrichment computed across 250 evidence-associated genes (147 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 147 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cardiac conduction	14	10.4×	3e-08	SCN5A, KCNH2, KCNJ2, SCN10A, TBX5, CAMK2D, CASQ2, AKAP9 (+6 more)
Muscle contraction	16	8.4×	3e-08	SCN5A, KCNH2, KCNJ2, SCN10A, TBX5, CAMK2D, CASQ2, AKAP9 (+8 more)
Phase 3 - rapid repolarisation	6	46.6×	2e-07	KCNH2, AKAP9, KCNE1, KCNE5, KCNE2, KCNQ1
Phase 2 - plateau phase	5	25.9×	2e-04	AKAP9, KCNE1, KCNE5, KCNE2, KCNQ1
Physiological factors	5	22.9×	3e-04	TBX5, CORIN, NKX2-5, GATA4, NPPA
Cardiogenesis	5	14.4×	0.003	TBX5, MYOCD, NKX2-5, GATA4, HAND2
YAP1- and WWTR1 (TAZ)-stimulated gene expression	4	20.7×	0.004	TBX5, NKX2-5, GATA4, NPPA
Potassium Channels	7	6.4×	0.011	KCNH2, KCNJ2, KCND3, KCNJ5, KCNN2, KCNN3, KCNQ1
RHOQ GTPase cycle	6	7.4×	0.014	CAV1, ARHGAP26, GOPC, ARHGAP21, GJA1, PAK2
Extra-nuclear estrogen signaling	6	7.0×	0.017	CAV1, CAV2, GNB4, HBEGF, ESR2, IGF1R
Cellular response to heat stress	4	10.7×	0.033	YWHAE, CAMK2D, SIRT1, BAG3
Neuronal System	11	3.3×	0.033	KCNH2, KCNJ2, TUBA8, CAMK2D, CHRNA1, KCND3, KCNJ5, KCNN2 (+3 more)
RHOJ GTPase cycle	5	6.8×	0.050	CAV1, ARHGAP26, ARHGAP21, GJA1, PAK2
Formation of the dystrophin-glycoprotein complex (DGC)	4	8.4×	0.072	SGCG, SNTA1, SSPN, HSPG2
Respiratory syncytial virus (RSV) attachment and entry	3	10.1×	0.165	LY96, HSPG2, IGF1R
Mineralocorticoid biosynthesis	2	19.4×	0.208	CGA, CYP21A2
CDC42 GTPase cycle	7	3.4×	0.208	WIPF1, FAM13B, CAV1, ARHGAP26, SH3PXD2A, ARHGAP21, PAK2
Ca2+ activated K+ channels	2	15.5×	0.243	KCNN2, KCNN3
G protein gated Potassium channels	2	15.5×	0.243	KCNJ2, KCNJ5
Activation of G protein gated Potassium channels	3	8.0×	0.243	KCNJ2, GNB4, KCNJ5
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	3	8.0×	0.243	KCNJ2, GNB4, KCNJ5
Interaction between L1 and Ankyrins	3	7.5×	0.243	SCN5A, SCN10A, ANK2
Nuclear Receptor transcription pathway	4	5.5×	0.243	THRB, NRBF2, ESR2, NR3C1
Cellular responses to stress	10	2.5×	0.243	RPS2, TUBA8, YWHAE, CAMK2D, SIRT1, LY96, CDK6, CDKN2C (+2 more)
PI3K events in ERBB4 signaling	2	14.1×	0.257	HBEGF, ERBB4
Phase 0 - rapid depolarisation	3	7.1×	0.257	SCN5A, SCN10A, CAMK2D
TCF dependent signaling in response to WNT	5	4.0×	0.257	SOX4, WNT3, WNT8A, CAV1, USP34
Transcriptional and post-translational regulation of MITF-M expression and activity	4	4.9×	0.266	TBX3, XPO1, YWHAE, SIRT1
Defective visual phototransduction due to OPN1SW loss of function	1	77.7×	0.297	OPN1SW
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	2	11.9×	0.297	YWHAE, CAV1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 211 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	17	30.2×	3e-18	SCN5A, HCN4, GJA5, KCNH2, KCNJ2, YWHAE, CAMK2D, CAV1 (+9 more)
regulation of ventricular cardiac muscle cell membrane repolarization	11	43.9×	1e-13	SCN5A, GJA5, KCNH2, SNTA1, WDR1, AKAP9, ANK2, KCNE1 (+3 more)
ventricular cardiac muscle cell action potential	10	47.0×	8e-13	SCN5A, GJA5, KCNH2, SNTA1, ANK2, KCNE1, KCNE5, KCNE2 (+2 more)
regulation of membrane repolarization	9	55.3×	2e-12	KCNH2, KCNJ2, YWHAE, CASQ2, AKAP6, AKAP9, KCNE5, KCNE2 (+1 more)
cardiac muscle contraction	10	19.0×	3e-08	SCN5A, TTN, KCNH2, CASQ2, NKX2-5, KCNE5, KCNQ1, MYBPC3 (+2 more)
regulation of heart rate	9	20.0×	1e-07	SCN5A, HCN4, SCN10A, SHOX2, SNTA1, CASQ2, ANK2, MYH6 (+1 more)
membrane repolarization during action potential	6	47.9×	1e-07	KCNH2, KCNJ2, KCNE1, KCNE5, KCNE2, KCNQ1
membrane repolarization during cardiac muscle cell action potential	6	47.9×	1e-07	KCNH2, KCNJ2, YWHAE, KCND3, KCNE1, KCNQ1
membrane repolarization during ventricular cardiac muscle cell action potential	6	47.9×	1e-07	KCNH2, KCND3, KCNE1, KCNE5, KCNE2, KCNQ1
regulation of heart contraction	8	18.8×	1e-06	THRB, CAMK2D, HBEGF, KCND3, KCNE5, KCNQ1, MYH6, PLN
regulation of cardiac muscle cell contraction	6	31.9×	3e-06	SCN5A, KCNJ2, GATA4, ANK2, MYBPC3, PLN
potassium ion export across plasma membrane	6	29.9×	4e-06	KCNH2, KCND3, KCNE1, KCNE5, KCNE2, KCNQ1
positive regulation of potassium ion transmembrane transport	6	28.2×	5e-06	KCNH2, KCNJ2, AKAP6, KCNE1, KCNE5, KCNQ1
sarcomere organization	8	14.5×	8e-06	TTN, WDR1, MYOZ1, CFL2, MYPN, SYNPO2L, MYBPC3, MYH6
atrial cardiac muscle cell action potential	5	39.9×	8e-06	SCN5A, GJA1, ANK2, KCNE5, KCNQ1
regulation of cardiac muscle contraction	6	25.2×	9e-06	HCN4, GJA5, SCN10A, NKX2-5, ANK2, SMAD7
SA node cell action potential	4	53.2×	4e-05	SCN5A, HCN4, GJA5, ANK2
cardiac muscle cell action potential involved in contraction	6	20.0×	4e-05	SCN5A, KCNJ2, SCN10A, KCNE1, KCNE2, PKP2
potassium ion transmembrane transport	11	7.1×	4e-05	HCN4, KCNH2, KCNJ2, SLC24A2, KCND3, KCNE1, KCNE2, KCNJ5 (+3 more)
regulation of atrial cardiac muscle cell membrane repolarization	4	45.6×	7e-05	SCN5A, KCNE5, KCNQ1, NPPA
regulation of potassium ion transmembrane transport	6	17.8×	7e-05	KCNH2, YWHAE, KCNE1, KCNE5, KCNE2, KCNN2
cardiac conduction system development	5	25.0×	9e-05	SCN5A, GJA5, NKX2-5, GJA1, NPPA
regulation of atrial cardiac muscle cell membrane depolarization	4	35.5×	2e-04	SCN5A, GJA5, SCN10A, TBX5
regulation of cardiac muscle cell action potential involved in regulation of contraction	4	35.5×	2e-04	HCN4, CAMK2D, CAV1, AKAP9
muscle contraction	8	7.9×	5e-04	TTN, HCN4, SNTA1, SSPN, MYOT, KCND3, MYH6, MYH7
ventricular septum morphogenesis	6	12.3×	5e-04	GJA5, SOX4, TBX3, NKX2-5, SMAD7, PITX2
ventricular cardiac muscle tissue morphogenesis	5	16.6×	6e-04	SMAD7, MYBPC3, MYH6, MYH7, PKP2
atrial septum morphogenesis	4	24.6×	9e-04	GJA5, TBX5, NKX2-5, GATA4
membrane repolarization	4	24.6×	9e-04	KCNH2, KCND3, KCNE1, KCNE2
muscle cell cellular homeostasis	5	15.4×	9e-04	CAV1, CFL2, CHRNA1, PLN, BAG3

Therapeutics

Drugs indicated for this disease

5 approved, 62 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Apixaban	Approved (phase 4)
Digoxin	Approved (phase 4)
Dofetilide	Approved (phase 4)
Heparin Sodium	Approved (phase 4)
Rivaroxaban	Approved (phase 4)
Abelacimab	Phase 3 (in late-stage trials)
Acenocoumarol	Phase 3 (in late-stage trials)
Acetylcysteine	Phase 3 (in late-stage trials)
Adenosine	Phase 3 (in late-stage trials)
Aliskiren	Phase 3 (in late-stage trials)
Amiodarone	Phase 3 (in late-stage trials)
Ascorbic Acid	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atenolol	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Avidin	Phase 3 (in late-stage trials)
Bisoprolol	Phase 3 (in late-stage trials)
Caffeine	Phase 3 (in late-stage trials)
Calcium Chloride	Phase 3 (in late-stage trials)
Candesartan	Phase 3 (in late-stage trials)
Carvedilol	Phase 3 (in late-stage trials)
Certoparin	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Colchicine	Phase 3 (in late-stage trials)
Dabigatran	Phase 3 (in late-stage trials)
Dabigatran Etexilate	Phase 3 (in late-stage trials)
Dapagliflozin	Phase 3 (in late-stage trials)
Diltiazem	Phase 3 (in late-stage trials)
Disopyramide	Phase 3 (in late-stage trials)
Dronedarone	Phase 3 (in late-stage trials)
Edoxaban	Phase 3 (in late-stage trials)
Enoxaparin Sodium	Phase 3 (in late-stage trials)
Flecainide	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Henagliflozin	Phase 3 (in late-stage trials)
Idrabiotaparinux Sodium	Phase 3 (in late-stage trials)
Indobufen	Phase 3 (in late-stage trials)
Irbesartan	Phase 3 (in late-stage trials)
Ivabradine	Phase 3 (in late-stage trials)
Landiolol	Phase 3 (in late-stage trials)
Levocarnitine	Phase 3 (in late-stage trials)
Metoprolol	Phase 3 (in late-stage trials)
Milvexian	Phase 3 (in late-stage trials)
Moricizine	Phase 3 (in late-stage trials)
Nifekalant	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Olmesartan	Phase 3 (in late-stage trials)
Prasugrel	Phase 3 (in late-stage trials)
Procainamide	Phase 3 (in late-stage trials)
Propafenone	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Quinidine	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Ranolazine	Phase 3 (in late-stage trials)
Remimazolam	Phase 3 (in late-stage trials)
Silybin A	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sotalol	Phase 3 (in late-stage trials)
Soybean Oil	Phase 3 (in late-stage trials)
Spironolactone	Phase 3 (in late-stage trials)
Ticagrelor	Phase 3 (in late-stage trials)
Valsartan	Phase 3 (in late-stage trials)
Vanoxerine	Phase 3 (in late-stage trials)
Verapamil	Phase 3 (in late-stage trials)
Vernakalant	Phase 3 (in late-stage trials)
Vitamin K	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alcohol, Betrixaban, Bupivacaine, Canakinumab, Celivarone, Darexaban, Eplerenone, Esmolol, Etripamil, Fondaparinux, Heparin, Hydrocortisone, Isoproterenol, Magnesium Sulfate Anhydrous, Melatonin, Metformin, Minocycline, Onabotulinumtoxina, Riluzole, Rimabotulinumtoxinb, Simvastatin, Ximelagatran.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 12 · Undrugged: 63

Druggability breadth: 84 of 250 evidence-associated genes (34%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN5A	BEPRIDIL
HCN4	IVABRADINE
KCNH2	CETIRIZINE
KCNE1	AMBRISENTAN
LMNA	BEPRIDIL
RPS2	GENTAMICIN SULFATE
SCN10A	IMIPRAMINE
SYK	FEDRATINIB
THRB	AMINOCAPROIC ACID
XPO1	SELINEXOR
CAMK2D	MOMELOTINIB
SIRT1	NIACINAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNA	823	4
KCNH2	706	4
THRB	117	4
SCN5A	108	4
SYK	54	4
CAMK2D	40	4
SCN10A	21	4
KCNE1	14	4
SIRT1	6	4
XPO1	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	KCNH2, LMNA, SCN5A
IMIPRAMINE	4	KCNH2, LMNA, SCN10A, SCN5A
DROPERIDOL	4	KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	KCNE1, KCNH2, SCN5A
PALONOSETRON	4	KCNE1, KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNH2, SCN10A, SCN5A
FEDRATINIB	4	CAMK2D, KCNH2, SCN5A, SYK
QUINIDINE	4	KCNH2, SCN5A
DARUNAVIR	4	KCNE1, KCNH2, SCN5A
DARIFENACIN	4	KCNE1, KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNE1, KCNH2, LMNA, SCN5A
RANOLAZINE	4	KCNH2, SCN5A
PIMOZIDE	4	KCNH2, LMNA, SCN10A, SCN5A
NIMODIPINE	4	LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	KCNH2, LMNA, SCN5A
AMLODIPINE	4	KCNH2, SCN5A
PHENYTOIN	4	KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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
SYK	873	Binding:863, Functional:10
SIRT1	645	Binding:642, ADMET:3
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
CAMK2D	338	Binding:337, Functional:1
THRB	169	Binding:129, Functional:40
XPO1	146	Binding:146
SCN10A	144	Binding:124, Functional:16, ADMET:4
KCNE1	117	Functional:63, Binding:47, ADMET:6, Toxicity:1
RPS2	90	Binding:90
TUBA8	73	Binding:72, Functional:1
KCNJ2	31	Binding:23, ADMET:8
HCN4	30	Binding:20, ADMET:5, Functional:4, Toxicity:1
BMP2	22	Binding:18, Functional:4
LMNA	12	Binding:9, Functional:3
WNT3	5	Functional:3, Binding:2
CAV1	5	Binding:5
YWHAE	4	Binding:4
USP3	3	Binding:3
SLC1A4	2	Binding:2
TTN	1	Binding:1
SLC24A2	1	Functional:1
TBX5	1	Binding:1
WDR1	1	Binding:1
AOPEP	1	ADMET:1
PRDM8	1	Binding:1
XPO7	1	Binding:1
CALU	1	Binding:1
COG5	1	Binding:1
UACA	1	Binding:1
ORMDL3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase
SYK	2.7.10.2, 2.7.12.1	non-specific protein-tyrosine kinase, dual-specificity kinase
UBE4B	2.3.2.27, 2.3.2.B12	RING-type E3 ubiquitin transferase,
CAMK2D	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
SIRT1	2.3.1.286	protein acetyllysine N-acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN5A	594
KCNH2	4,851
KCNE1	117
SCN10A	144
SYK	873
THRB	169
XPO1	146
CAMK2D	338
SIRT1	645

Pharmacogenomics

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

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

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	KCNH2, LMNA, SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	LMNA, SCN5A
DIBUCAINE	4	KCNH2, LMNA, SCN5A
IMIPRAMINE	4	KCNH2, LMNA, SCN10A, SCN5A
DROPERIDOL	4	KCNH2, LMNA, SCN5A
PONATINIB	4	KCNH2, SCN5A
DULOXETINE	4	KCNE1, KCNH2, SCN5A
PALONOSETRON	4	KCNE1, KCNH2, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	LMNA, SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	KCNH2, SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNH2, SCN10A, SCN5A
FEDRATINIB	4	CAMK2D, KCNH2, SCN5A, SYK
QUINIDINE	4	KCNH2, SCN5A
DARUNAVIR	4	KCNE1, KCNH2, SCN5A
DARIFENACIN	4	KCNE1, KCNH2, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNE1, KCNH2, LMNA, SCN5A
PIMOZIDE	4	KCNH2, LMNA, SCN10A, SCN5A
NIMODIPINE	4	LMNA, SCN5A
FELODIPINE	4	LMNA, SCN5A
NICARDIPINE	4	KCNH2, LMNA, SCN5A
AMLODIPINE	4	KCNH2, SCN5A
PHENYTOIN	4	KCNH2, SCN5A
PALIPERIDONE	4	KCNH2, SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	SCN5A, HCN4, KCNH2, KCNE1, LMNA, RPS2, SCN10A, SYK, THRB, XPO1 (+2 more)
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	6	TTN, KCNJ2, MYBPC3, OPN1SW, SORL1, MYOT
D	Druggable family + AlphaFold only, no drug	3	KCNE5, USP3, AOPEP
E	Difficult family or no structure, no drug	54	GJA5, SHOX2, SOX4, RNF11, RPL3L, ATXN1, BMP2, SGCG, SLC1A4, SLC24A2 (+44 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GJA5	0	SCN5A
SHOX2	0	HCN4
KCNE5	0	KCNE1
SNTA1	0	SCN5A
XPO7	1	XPO1
SYNE2	0	LMNA
TTN	1	—
KCNJ2	31	—
SOX4	0	—
MYBPC3	0	—
RNF11	0	—
OPN1SW	0	—
RPL3L	0	—
ATXN1	0	—
BMP2	22	—
SGCG	0	—
SLC1A4	2	—
SLC24A2	1	—
SLC27A6	0	—
SLIT1	0	—
SORL1	0	—
SOX15	0	—
SSPN	0	—
STC2	0	—
TBX3	0	—
TBX5	1	—
TLE3	0	—
TNFSF12	0	—
MYOT	0	—
TUBA8	73	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3,017.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	453
PHASE4	284
PHASE3	195
PHASE2	101
PHASE1	31
PHASE2/PHASE3	16
PHASE1/PHASE2	11
EARLY_PHASE1	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02347111	PHASE4	RECRUITING	Pharmacogenetic Study of Antiarrhythmic Drugs for Atrial Fibrillation
NCT03129490	PHASE4	ACTIVE_NOT_RECRUITING	The Danish Non-vitamin K Antagonist Oral Anticoagulation Study in Patients With Atrial Fibrillation
NCT03445949	PHASE4	RECRUITING	Optimal Antiplatelet Therapy Following Left Atrial Appendage Closure
NCT03603912	PHASE4	ACTIVE_NOT_RECRUITING	Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)
NCT03833089	PHASE4	ACTIVE_NOT_RECRUITING	Targeted Potassium Levels for Prevention of ICD Therapy
NCT03856632	PHASE4	ACTIVE_NOT_RECRUITING	Liraglutide Effect in Atrial Fibrillation
NCT03868150	PHASE4	RECRUITING	Prevention of Postop Atrial Fibrillation Through Intraoperative Inducibility of Atrial Fibrillation and Amiodarone Treatment
NCT03950076	PHASE4	ACTIVE_NOT_RECRUITING	EdoxabaN foR IntraCranial Hemorrhage Survivors With Atrial Fibrillation (ENRICH-AF)
NCT03968393	PHASE4	RECRUITING	Anticoagulation for Stroke Prevention In Patients With Recent Episodes of Atrial Fibrillation Occurring Transiently With Stress
NCT04045093	PHASE4	ACTIVE_NOT_RECRUITING	Dabigatran for Mitral Stenosis Atrial Fibrillation
NCT04111419	PHASE4	ACTIVE_NOT_RECRUITING	Intensive Management of Blood Pressure and Cholesterol in Elderly Chinese With Hypertension and Atrial Fibrillation
NCT04160000	PHASE4	RECRUITING	Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure
NCT04250116	PHASE4	ACTIVE_NOT_RECRUITING	Appropriate Duration of Anti-Platelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug Eluting Stents
NCT04436978	PHASE4	RECRUITING	What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?
NCT04642430	PHASE4	RECRUITING	COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
NCT04700826	PHASE4	RECRUITING	Preventing Stroke, Premature Death and Cognitive Decline in a Broader Community of Patients With Atrial Fibrillation
NCT05305612	PHASE4	ENROLLING_BY_INVITATION	Optimal PeriproCeduraL AnticOagulation in Structural Transseptal Interventions
NCT05508256	PHASE4	RECRUITING	CAtheter-Based Ablation of Atrial Fibrillation Compared to Conventional Treatment in Patients With Heart Failure With Preserved Ejection Fraction
NCT05660811	PHASE4	RECRUITING	Optimal Antiplatelet Therapy Following Left Atrial Appendage Closure in Dialyzed Patients
NCT05844501	PHASE4	RECRUITING	Ondansetron for the Management of Atrial Fibrillation
NCT05955365	PHASE4	RECRUITING	Monotherapy With P2Y12 Inhibitors in Patients With Atrial fIbrillation Undergoing Supraflex Stent Implantation
NCT06108414	PHASE4	RECRUITING	Low-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation
NCT06184633	PHASE4	RECRUITING	DUTCH Weight Control in Atrial Fibrillation Study
NCT06187311	PHASE4	RECRUITING	Clinical Trial to Evaluate Efficacy and Safety of Rivaroxaban 15mg and 20mg in Patients With Non-valvular Atrial Fibrillation
NCT06212674	PHASE4	RECRUITING	Single-stage Pulmonary Vein Isolation Combined With Percutaneous Left Atrial Appendage Occluder Implantation in Patients With Recent Onset Ischemic Stroke and Atrial Fibrillation
NCT06401616	PHASE4	RECRUITING	Can Patients With Atrial Fibrillation Safely Discontinue Anticoagulant Therapy After Cardiac Surgery? (ATLAAC)
NCT06486792	PHASE4	NOT_YET_RECRUITING	Stroke Prevention In Ischemic Stroke With Covert Atrial Fibrillation
NCT06528262	PHASE4	RECRUITING	Effect of Enavogliflozin on Recurrence of Atrial Fibrillation After Catheter Ablation
NCT06645249	PHASE4	NOT_YET_RECRUITING	Evaluation of Cardioverter Capacity of Amiodarone Pre-electrical Cardioversion in Persistent Atrial Fibrillation
NCT06798714	PHASE4	RECRUITING	The Effect of Colchicine on the Occurrence of Atrial Fibrillation After Cardiac Surgery
NCT06953726	PHASE4	NOT_YET_RECRUITING	Comparing the Safety and Efficacy of Apixaban and Rivaroxaban
NCT07027969	PHASE4	NOT_YET_RECRUITING	Metabolic Surgery for Atrial Fibrillation Elimination
NCT07135258	PHASE4	NOT_YET_RECRUITING	Atrial Fibrillation: In Search for the Optimal Target for Rate Control
NCT07237308	PHASE4	NOT_YET_RECRUITING	BEACON-AA: Apixaban With or Without Clopidogrel in Stroke Patients With Atrial Fibrillation and Cerebral Atherosclerosis
NCT07238452	PHASE4	NOT_YET_RECRUITING	Optimising Pacing Therapy, Integrated Medical Therapy, and Catheter AbLation for Atrial Fibrillation in Heart Failure Trial
NCT07250763	PHASE4	ACTIVE_NOT_RECRUITING	Therapeutic Initial Heparin Dosing for Patients With Clots or Certain Heart Conditions Admitted to the Hospital
NCT07270848	PHASE4	NOT_YET_RECRUITING	Dronedarone Rhythm Intervention for Early Atrial Fibrillation
NCT07275697	PHASE4	NOT_YET_RECRUITING	Waiting on Atrial Fibrillation Intervention Therapy (WAIT) Study
NCT07389941	PHASE4	NOT_YET_RECRUITING	Semaglutide PrIor to CathEeter Ablation in Patients With Atrial Fibrillation
NCT07405671	PHASE4	NOT_YET_RECRUITING	Flecainide Safety in Patients With Coronary Artery Disease and Atrial Fibrillation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMIODARONE	4	128
DABIGATRAN ETEXILATE	4	46
FLECAINIDE	4	30
WARFARIN	4	29
APIXABAN	4	26
DRONEDARONE	4	21
RIVAROXABAN	4	21
EDOXABAN	4	20
VERNAKALANT	4	19
DILTIAZEM	4	18
METOPROLOL	4	17
COLCHICINE	4	13
BISOPROLOL	4	12
PHENPROCOUMON	4	9
TICAGRELOR	4	8
DIGOXIN	4	7
PROPAFENONE	4	7
SOTALOL	4	6
ASPIRIN	4	5
LANDIOLOL	4	5
SPIRONOLACTONE	4	5
DAPAGLIFLOZIN	4	4
FISH OIL	4	4
IVABRADINE	4	4
PROCAINAMIDE	4	4
RANOLAZINE	4	4
SEMAGLUTIDE	4	4
ASCORBIC ACID	4	3
CARVEDILOL	4	3
IRBESARTAN	4	3