Familial atrial fibrillation

disease

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Also known as atrial fibrillation autosomal dominantatrial fibrillation, familialautosomal dominant atrial fibrillationhereditary atrial fibrillation (disease)

Summary

Familial atrial fibrillation (MONDO:0018054) is a disease (an umbrella term covering 18 Mondo subtypes) with 18 cohort genes and 2 clinical trials. The dominant Reactome pathway is Muscle contraction (10 cohort genes).

At a glance

Umbrella term: 18 Mondo subtypes
Cohort genes: 18
ClinVar variants: 2
Phenotypes (HPO): 11
Clinical trials: 2

Clinical features

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001279	Syncope	Frequent (30-79%)
HP:0001962	Palpitations	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002321	Vertigo	Frequent (30-79%)
HP:0003546	Exercise intolerance	Frequent (30-79%)
HP:0005110	Atrial fibrillation	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0001727	Thromboembolic stroke	Occasional (5-29%)
HP:0001907	Thromboembolism	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	familial atrial fibrillation
Mondo ID	MONDO:0018054
OMIM	608583
Orphanet	334
DOID	DOID:0050650
ICD-11	45855978
SNOMED CT	715395008
UMLS	C3468561
MedGen	894635
GARD	0009740
Is cancer (heuristic)	no

Also known as: atrial fibrillation autosomal dominant · atrial fibrillation, familial · autosomal dominant atrial fibrillation · hereditary atrial fibrillation (disease)

Data availability: 2 ClinVar variants · 17 GenCC gene-disease records · 33 cell lines.

Disease family

An umbrella term covering 18 Mondo subtypes.

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

Related subtypes (2): persistent atrial fibrillation, paroxysmal atrial fibrillation

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
224067	NM_002476.2(MYL4):c.31G>A (p.Glu11Lys)	MYL4	Pathogenic	criteria provided, single submitter
488160	NM_001105206.3(LAMA4):c.3742A>G (p.Ile1248Val)	LAMA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 158 · Orphanet: 67 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
GATA4	Definitive	Autosomal dominant	atrial septal defect 2	15
GATA6	Definitive	Autosomal dominant	atrial septal defect 9	16
NKX2-5	Definitive	Autosomal dominant	atrial septal defect 7	17
GJA5	Strong	Autosomal dominant	atrial fibrillation, familial, 11	6
KCNJ2	Strong	Autosomal dominant	atrial fibrillation, familial, 9	15
KCNQ1	Strong	Autosomal dominant	atrial fibrillation, familial, 3	12
MYL4	Strong	Autosomal dominant	atrial fibrillation, familial, 18	2
KCNA5	Moderate	Autosomal dominant	atrial fibrillation, familial, 7	4
NPPA	Moderate	Autosomal dominant	atrial fibrillation, familial, 6	6
SCN2B	Moderate	Autosomal dominant	atrial fibrillation, familial, 14	7
GATA5	Supportive	Autosomal dominant	familial atrial fibrillation	7
KCNE2	Supportive	Autosomal dominant	familial atrial fibrillation	2
NUP155	Supportive	Autosomal dominant	familial atrial fibrillation	3
PITX2	Supportive	Autosomal dominant	familial atrial fibrillation	15
SCN3B	Supportive	Autosomal dominant	familial atrial fibrillation	4
SCN4B	Supportive	Autosomal dominant	familial atrial fibrillation	4
SCN5A	Supportive	Autosomal dominant	atrial standstill	23

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYL4	Orphanet:334	Hereditary atrial fibrillation
SCN2B	Orphanet:130	Brugada syndrome
SCN2B	Orphanet:334	Hereditary atrial fibrillation
SCN4B	Orphanet:101016	Romano-Ward syndrome
SCN4B	Orphanet:334	Hereditary atrial fibrillation
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
GATA5	Orphanet:3303	Tetralogy of Fallot
GATA5	Orphanet:334	Hereditary atrial fibrillation
GATA5	Orphanet:402075	Familial bicuspid aortic valve
SCN3B	Orphanet:130	Brugada syndrome
SCN3B	Orphanet:334	Hereditary atrial fibrillation
NKX2-5	Orphanet:101351	Familial isolated congenital asplenia
NKX2-5	Orphanet:1479	Atrial septal defect-atrioventricular conduction defects syndrome
NKX2-5	Orphanet:1627	Deletion 5q35 syndrome
NKX2-5	Orphanet:2248	Hypoplastic left heart syndrome
NKX2-5	Orphanet:3303	Tetralogy of Fallot
NKX2-5	Orphanet:334	Hereditary atrial fibrillation
NKX2-5	Orphanet:402075	Familial bicuspid aortic valve
NKX2-5	Orphanet:871	Hereditary progressive cardiac conduction defect
NKX2-5	Orphanet:95712	Thyroid ectopia
NKX2-5	Orphanet:95713	Athyreosis
NKX2-5	Orphanet:99103	Atrial septal defect, ostium secundum type
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
GATA6	Orphanet:2140	Congenital diaphragmatic hernia
GATA6	Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
GATA6	Orphanet:3303	Tetralogy of Fallot
GATA6	Orphanet:334	Hereditary atrial fibrillation
GATA6	Orphanet:665044	Common arterial trunk with aortic dominance
GATA6	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
GATA6	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA6	Orphanet:99103	Atrial septal defect, ostium secundum type
GJA5	Orphanet:3303	Tetralogy of Fallot
GJA5	Orphanet:334	Hereditary atrial fibrillation
KCNA5	Orphanet:334	Hereditary atrial fibrillation
KCNE2	Orphanet:101016	Romano-Ward syndrome
KCNE2	Orphanet:334	Hereditary atrial fibrillation

Cohort genes → proteins

18 cohort genes, 18 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	18

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYL4	HGNC:7585	ENSG00000198336	P12829	Myosin light chain 4	gencc,clinvar
SCN2B	HGNC:10589	ENSG00000149575	O60939	Sodium channel regulatory subunit beta-2	gencc
SCN4B	HGNC:10592	ENSG00000177098	Q8IWT1	Sodium channel regulatory subunit beta-4	gencc
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	gencc
GATA5	HGNC:15802	ENSG00000130700	Q9BWX5	Transcription factor GATA-5	gencc
SCN3B	HGNC:20665	ENSG00000166257	Q9NY72	Sodium channel regulatory subunit beta-3	gencc
NKX2-5	HGNC:2488	ENSG00000183072	P52952	Homeobox protein Nkx-2.5	gencc
GATA4	HGNC:4173	ENSG00000136574	P43694	Transcription factor GATA-4	gencc
GATA6	HGNC:4174	ENSG00000141448	Q92908	Transcription factor GATA-6	gencc
GJA5	HGNC:4279	ENSG00000265107	P36382	Gap junction alpha-5 protein	gencc
KCNA5	HGNC:6224	ENSG00000130037	P22460	Potassium voltage-gated channel subfamily A member 5	gencc
KCNE2	HGNC:6242	ENSG00000159197	Q9Y6J6	Potassium voltage-gated channel subfamily E member 2	gencc
KCNJ2	HGNC:6263	ENSG00000123700	P63252	Inward rectifier potassium channel 2	gencc
KCNQ1	HGNC:6294	ENSG00000053918	P51787	Potassium voltage-gated channel subfamily KQT member 1	gencc
NPPA	HGNC:7939	ENSG00000175206	P01160	Natriuretic peptides A	gencc
NUP155	HGNC:8063	ENSG00000113569	O75694	Nuclear pore complex protein Nup155	gencc
PITX2	HGNC:9005	ENSG00000164093	Q99697	Pituitary homeobox 2	gencc
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYL4	Myosin light chain 4	Regulatory light chain of myosin.
SCN2B	Sodium channel regulatory subunit beta-2	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
SCN4B	Sodium channel regulatory subunit beta-4	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization 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.
GATA5	Transcription factor GATA-5	Transcription factor required during cardiovascular development.
SCN3B	Sodium channel regulatory subunit beta-3	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
NKX2-5	Homeobox protein Nkx-2.5	Transcription factor required for the development of the heart and the spleen.
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.
GATA6	Transcription factor GATA-6	Transcriptional activator.
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.
KCNA5	Potassium voltage-gated channel subfamily A member 5	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
KCNE2	Potassium voltage-gated channel subfamily E member 2	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.
KCNJ2	Inward rectifier potassium channel 2	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
KCNQ1	Potassium voltage-gated channel subfamily KQT member 1	Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon.
NPPA	Natriuretic peptides A	Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism.
NUP155	Nuclear pore complex protein Nup155	Essential component of nuclear pore complex.
PITX2	Pituitary homeobox 2	May play a role in myoblast differentiation.
LAMA4	Laminin subunit alpha-4	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Protein-family classification

Druggable: 8 · Difficult: 5 · Unknown: 5 · Druggable fraction: 0.44

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	5	31.0×	2e-06
Antibody/Immunoglobulin	3	4.9×	0.045
Transcription factor	5	2.3×	0.077
Other/Unknown	5	0.5×	0.996

Per-gene assignment

Symbol	Family	Druggable?	InterPro (top 3)
MYL4	Other/Unknown	no	EF_hand_dom, EF-hand-dom_pair, CALM/Myosin/TropC-like
SCN2B	Antibody/Immunoglobulin	yes	Myelin_P0-rel, Ig_sub, Ig-like_dom
SCN4B	Antibody/Immunoglobulin	yes	Myelin_P0-rel, Ig_sub, Ig-like_dom
SCN5A	Ion channel	yes	Na_channel_asu, Ion_trans_dom, Na_channel_a5su
GATA5	Transcription factor	no	Znf_GATA, GATA_N, Znf_NHR/GATA
SCN3B	Antibody/Immunoglobulin	yes	Ig_sub, Ig-like_dom, Ig_V-set
NKX2-5	Transcription factor	no	HD, Homeodomain-like_sf, Homeobox_CS
GATA4	Transcription factor	no	Znf_GATA, GATA_N, Znf_NHR/GATA
GATA6	Transcription factor	no	Znf_GATA, GATA_N, Znf_NHR/GATA
GJA5	Other/Unknown	no	Connexin, Connexin40, Connexin_N
KCNA5	Ion channel	yes	BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
KCNE2	Ion channel	yes	K_chnl_KCNE, K_chnl_volt-dep_bsu_KCNE2
KCNJ2	Ion channel	yes	K_chnl_inward-rec_Kir2.1, K_chnl_inward-rec_Kir_cyto, K_chnl_inward-rec_Kir_N
KCNQ1	Ion channel	yes	K_chnl_volt-dep_KCNQ, Ion_trans_dom, K_chnl_volt-dep_KCQN1
NPPA	Other/Unknown	no	Natr_peptide, Natriuretic_peptide_atrial, Natr_peptide_CS
NUP155	Other/Unknown	no	Nucleoporin_Nup155, Nucleoporin_Nup133/Nup155_C, Nucleoporin_Nup133/Nup155_N
PITX2	Transcription factor	no	HD, OAR_dom, Homeodomain-like_sf
LAMA4	Other/Unknown	no	EGF, Laminin_G, LE_dom

Expression context

Cohort genes with no expression data: 0.

13 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)	18
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac atrium	4
right atrium auricular region	4
cardiac muscle of right atrium	3
middle temporal gyrus	2
apex of heart	2
heart left ventricle	2
jejunal mucosa	2
cerebellar cortex	1
lateral nuclear group of thalamus	1
dorsal root ganglion	1
lateral globus pallidus	1
putamen	1
cardiac ventricle	1
ileal mucosa	1
left uterine tube	1
cortical plate	1
orbitofrontal cortex	1
duodenum	1
germinal epithelium of ovary	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYL4	186	broad	marker	right atrium auricular region, cardiac atrium, cardiac muscle of right atrium
SCN2B	182	broad	yes	middle temporal gyrus, lateral nuclear group of thalamus, cerebellar cortex
SCN4B	223	broad	marker	lateral globus pallidus, dorsal root ganglion, putamen
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
GATA5	106	broad	yes	ileal mucosa, left uterine tube, jejunal mucosa
SCN3B	193	broad	marker	middle temporal gyrus, orbitofrontal cortex, cortical plate
NKX2-5	98	broad	yes	apex of heart, right atrium auricular region, cardiac atrium
GATA4	85	broad	marker	right atrium auricular region, heart left ventricle, duodenum
GATA6	204	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, jejunal mucosa
GJA5	190	broad	marker	placenta, right coronary artery, left coronary artery
KCNA5	179	broad	marker	cardiac muscle of right atrium, blood vessel layer, cardiac atrium
KCNE2	161	tissue_specific	yes	body of stomach, pylorus, cardia of stomach
KCNJ2	256	ubiquitous	marker	inferior vagus X ganglion, skeletal muscle tissue of rectus abdominis, dorsal motor nucleus of vagus nerve
KCNQ1	132	broad	marker	left adrenal gland cortex, left adrenal gland, right adrenal gland cortex
NPPA	218	tissue_specific	marker	cardiac muscle of right atrium, cardiac atrium, right atrium auricular region
NUP155	238	ubiquitous	marker	sperm, male germ cell, left testis
PITX2	166	broad	marker	gingiva, biceps brachii, gingival epithelium
LAMA4	268	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, nerve

Protein interactions among cohort

Intra-cohort edges: 19.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA4	4,994
NUP155	3,663
KCNQ1	3,235
NPPA	2,701
LAMA4	2,688
GATA5	2,434
PITX2	2,389
NKX2-5	2,355
KCNA5	2,288
SCN3B	2,219

Intra-cohort edges

A	B	Sources
GATA4	NKX2-5	biogrid_interaction, intact, string_interaction
GATA4	NPPA	string_interaction
GATA5	NKX2-5	string_interaction
GJA5	NKX2-5	string_interaction
GJA5	NPPA	string_interaction
GJA5	SCN5A	string_interaction
KCNA5	KCNE2	string_interaction
KCNA5	SCN5A	string_interaction
KCNE2	KCNQ1	biogrid_interaction, string_interaction
KCNE2	SCN3B	string_interaction
KCNE2	SCN4B	string_interaction
KCNE2	SCN5A	string_interaction
KCNQ1	SCN5A	string_interaction
NKX2-5	NPPA	string_interaction
SCN2B	SCN3B	string_interaction
SCN2B	SCN5A	string_interaction
SCN3B	SCN4B	string_interaction
SCN3B	SCN5A	string_interaction
SCN4B	SCN5A	string_interaction

Structural data

PDB: 12 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN2B	O60939	35
KCNQ1	P51787	28
SCN5A	Q14524	16
NPPA	P01160	13
NUP155	O75694	10
SCN4B	Q8IWT1	5
NKX2-5	P52952	4
SCN3B	Q9NY72	3
GATA4	P43694	3
KCNJ2	P63252	3
PITX2	Q99697	3
KCNE2	Q9Y6J6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYL4	P12829	90.85
LAMA4	Q16363	73.75
KCNA5	P22460	72.64
GJA5	P36382	70.35
GATA5	Q9BWX5	59.91
GATA6	Q92908	53.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 91. Enrichment computed across 18 evidence-associated genes (18 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 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Muscle contraction	10	42.9×	4e-13	MYL4, SCN2B, SCN4B, SCN5A, SCN3B, KCNA5, KCNE2, KCNJ2 (+2 more)
Cardiac conduction	9	54.4×	7e-13	SCN2B, SCN4B, SCN5A, SCN3B, KCNA5, KCNE2, KCNJ2, KCNQ1 (+1 more)
Interaction between L1 and Ankyrins	4	81.9×	4e-06	SCN2B, SCN4B, SCN5A, SCN3B
Phase 0 - rapid depolarisation	4	76.9×	4e-06	SCN2B, SCN4B, SCN5A, SCN3B
Phase 3 - rapid repolarisation	3	190.3×	7e-06	KCNA5, KCNE2, KCNQ1
YAP1- and WWTR1 (TAZ)-stimulated gene expression	3	126.9×	2e-05	NKX2-5, GATA4, NPPA
Physiological factors	3	112.0×	3e-05	NKX2-5, GATA4, NPPA
Cardiogenesis	3	70.5×	1e-04	NKX2-5, GATA4, GATA6
L1CAM interactions	4	26.7×	1e-04	SCN2B, SCN4B, SCN5A, SCN3B
Sensory perception of taste	3	56.0×	2e-04	SCN2B, SCN4B, KCNJ2
Phase 2 - plateau phase	2	84.6×	0.002	KCNE2, KCNQ1
Formation of definitive endoderm	2	79.3×	0.002	GATA4, GATA6
Potassium Channels	3	22.4×	0.002	KCNA5, KCNJ2, KCNQ1
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	2	66.8×	0.003	GATA4, GATA6
Axon guidance	4	10.0×	0.003	SCN2B, SCN4B, SCN5A, SCN3B
Nervous system development	4	9.5×	0.004	SCN2B, SCN4B, SCN5A, SCN3B
Sensory Perception	3	15.9×	0.004	SCN2B, SCN4B, KCNJ2
Sensory perception of sweet, bitter, and umami (glutamate) taste	2	30.9×	0.009	SCN2B, SCN4B
Voltage gated Potassium channels	2	27.0×	0.011	KCNA5, KCNQ1
Factors involved in megakaryocyte development and platelet production	3	11.1×	0.011	GATA5, GATA4, GATA6
Developmental Lineage of Pancreatic Ductal Cells	2	25.4×	0.012	GATA4, LAMA4
Sensory perception of sour taste	1	317.2×	0.013	KCNJ2
Classical Kir channels	1	158.6×	0.024	KCNJ2
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	158.6×	0.024	PITX2
Neuronal System	3	7.4×	0.026	KCNA5, KCNJ2, KCNQ1
Formation of lateral plate mesoderm	1	126.9×	0.028	GATA4
G protein gated Potassium channels	1	63.4×	0.051	KCNJ2
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	1	63.4×	0.051	GATA6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	48.8×	0.064	GATA4
Inwardly rectifying K+ channels	1	39.6×	0.073	KCNJ2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart rate by cardiac conduction	9	187.2×	5e-17	SCN2B, SCN4B, SCN5A, SCN3B, GJA5, KCNA5, KCNE2, KCNJ2 (+1 more)
cardiac muscle contraction	7	156.0×	2e-12	MYL4, SCN2B, SCN4B, SCN5A, SCN3B, NKX2-5, KCNQ1
cardiac muscle cell action potential involved in contraction	6	234.1×	9e-12	SCN2B, SCN4B, SCN5A, SCN3B, KCNE2, KCNJ2
atrial cardiac muscle cell action potential	5	468.1×	2e-11	SCN5A, SCN3B, KCNA5, KCNQ1, NUP155
membrane depolarization during cardiac muscle cell action potential	5	390.1×	4e-11	SCN2B, SCN4B, SCN5A, SCN3B, KCNJ2
ventricular cardiac muscle cell action potential	5	275.4×	3e-10	SCN5A, SCN3B, GJA5, KCNE2, KCNQ1
positive regulation of sodium ion transport	5	234.1×	5e-10	SCN2B, SCN4B, SCN5A, SCN3B, NKX2-5
regulation of ventricular cardiac muscle cell membrane repolarization	5	234.1×	5e-10	SCN4B, SCN5A, GJA5, KCNE2, KCNQ1
regulation of atrial cardiac muscle cell membrane repolarization	4	535.0×	1e-09	SCN5A, KCNA5, KCNQ1, NPPA
regulation of atrial cardiac muscle cell membrane depolarization	4	416.1×	4e-09	SCN2B, SCN5A, SCN3B, GJA5
cardiac conduction system development	4	234.1×	5e-08	SCN5A, NKX2-5, GJA5, NPPA
atrioventricular node development	3	468.1×	5e-07	NKX2-5, GATA4, GATA6
regulation of ventricular cardiac muscle cell membrane depolarization	3	468.1×	5e-07	SCN5A, SCN3B, GJA5
SA node cell action potential	3	468.1×	5e-07	SCN5A, SCN3B, GJA5
aortic valve morphogenesis	4	96.0×	2e-06	GATA5, NKX2-5, GATA4, NPPA
membrane depolarization during action potential	3	280.9×	2e-06	SCN2B, SCN5A, SCN3B
membrane repolarization during action potential	3	280.9×	2e-06	KCNE2, KCNJ2, KCNQ1
intestinal epithelial cell differentiation	3	255.3×	3e-06	GATA5, GATA4, GATA6
regulation of membrane repolarization	3	216.1×	5e-06	KCNE2, KCNJ2, KCNQ1
atrial septum morphogenesis	3	216.1×	5e-06	NKX2-5, GATA4, GJA5
regulation of cardiac muscle cell contraction	3	187.2×	8e-06	SCN5A, GATA4, KCNJ2
potassium ion export across plasma membrane	3	175.5×	9e-06	KCNA5, KCNE2, KCNQ1
positive regulation of heart rate	3	117.0×	3e-05	SCN3B, KCNQ1, NPPA
pulmonary myocardium development	2	624.1×	5e-05	NKX2-5, PITX2
AV node cell action potential	2	468.1×	9e-05	SCN4B, SCN5A
potassium ion transmembrane transport	4	30.2×	1e-04	KCNA5, KCNE2, KCNJ2, KCNQ1
ventricular septum morphogenesis	3	72.0×	1e-04	NKX2-5, GJA5, PITX2
embryonic heart tube left/right pattern formation	2	312.1×	2e-04	NKX2-5, PITX2
membrane repolarization during atrial cardiac muscle cell action potential	2	312.1×	2e-04	KCNA5, KCNQ1
negative regulation of delayed rectifier potassium channel activity	2	312.1×	2e-04	KCNE2, KCNQ1

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 6 · Undrugged: 12

Druggability breadth: 10 of 18 evidence-associated genes (56%) 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
KCNA5	DRONEDARONE HYDROCHLORIDE
KCNQ1	AMBRISENTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN5A	108	4
KCNQ1	15	4
KCNA5	8	4
SCN2B	2	2
NPPA	1	2
NUP155	1	2
MYL4	0	0
SCN4B	0	0
GATA5	0	0
SCN3B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	SCN5A
DULOXETINE	4	KCNQ1, SCN5A
PALONOSETRON	4	KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNA5, SCN5A
FEDRATINIB	4	SCN5A
QUINIDINE	4	KCNA5, SCN5A
DARUNAVIR	4	KCNQ1, SCN5A
DARIFENACIN	4	KCNQ1, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNQ1, SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
KCNQ1	179	Binding:96, Functional:64, ADMET:14, Toxicity:5
KCNA5	152	Binding:130, Functional:14, ADMET:5, Toxicity:3
KCNJ2	31	Binding:23, ADMET:8
SCN2B	9	ADMET:4, Binding:3, Toxicity:2
NUP155	9	Binding:9
GATA4	5	Binding:5
NPPA	5	Binding:5
MYL4	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN5A	594
KCNA5	152
KCNQ1	179

Pharmacogenomics

Cohort genes with a PharmGKB record: 18; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	SCN5A
DULOXETINE	4	KCNQ1, SCN5A
PALONOSETRON	4	KCNQ1, SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	KCNA5, SCN5A
FEDRATINIB	4	SCN5A
QUINIDINE	4	KCNA5, SCN5A
DARUNAVIR	4	KCNQ1, SCN5A
DARIFENACIN	4	KCNQ1, SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	KCNQ1, SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SCN5A, KCNA5, KCNQ1
B	Phased (≥1) drug, not yet approved	3	SCN2B, NPPA, NUP155
C	Druggable family + PDB, no drug	4	SCN4B, SCN3B, KCNE2, KCNJ2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	MYL4, GATA5, NKX2-5, GATA4, GATA6, GJA5, PITX2, LAMA4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SCN4B	0	SCN5A
SCN3B	0	SCN2B, SCN5A
GJA5	0	SCN5A
KCNE2	0	KCNQ1, SCN5A
MYL4	1	—
GATA5	0	—
NKX2-5	0	—
GATA4	5	—
GATA6	0	—
KCNJ2	31	—
PITX2	0	—
LAMA4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04075994	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial
NCT04076020	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial in Rural Pennsylvania Counties

Cohort genes: MYL4, SCN2B, SCN4B, SCN5A, GATA5, SCN3B, NKX2-5, GATA4, GATA6, GJA5, KCNA5, KCNE2, KCNJ2, KCNQ1, NPPA, NUP155, PITX2, LAMA4