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Atlas / Disease / Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation

disease
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Also known as paroxymsal AFibparoxysmal AF

Summary

Paroxysmal atrial fibrillation (MONDO:1030011) is a disease with 4 cohort genes and 227 clinical trials. Top therapeutic interventions include flecainide, antazoline, and rosuvastatin.

At a glance

  • Cohort genes: 4
  • ClinVar variants: 5
  • Clinical trials: 227

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameparoxysmal atrial fibrillation
Mondo IDMONDO:1030011
ICD-10-CMI48.0
ICD-11542703670
NCITC80391
SNOMED CT282825002
UMLSC0235480
MedGen115990
Is cancer (heuristic)no

Also known as: paroxymsal AFib · paroxysmal AF

Data availability: 5 ClinVar variants.

Disease family

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

Related subtypes (2): familial atrial fibrillation, persistent 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

5 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
518526NM_000722.4(CACNA2D1):c.1648G>T (p.Asp550Tyr)CACNA2D1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
52947NM_000218.3(KCNQ1):c.1066_1071del (p.Gln356_Gln357del)KCNQ1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
42626NM_000256.3(MYBPC3):c.2497G>A (p.Ala833Thr)MYBPC3Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
42671NM_000256.3(MYBPC3):c.2938C>T (p.Arg980Cys)MYBPC3Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
222698NM_020774.4(MIB1):c.742A>G (p.Ile248Val)MIB1Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CACNA2D1Orphanet:130Brugada syndrome
CACNA2D1Orphanet:442835Non-specific early-onset epileptic encephalopathy
CACNA2D1Orphanet:51083Congenital short QT syndrome
MIB1Orphanet:54260Left ventricular noncompaction
KCNQ1Orphanet:101016Romano-Ward syndrome
KCNQ1Orphanet:334Hereditary atrial fibrillation
KCNQ1Orphanet:51083Congenital short QT syndrome
KCNQ1Orphanet:90647Jervell and Lange-Nielsen syndrome
MYBPC3Orphanet:154Familial isolated dilated cardiomyopathy
MYBPC3Orphanet:54260Left ventricular noncompaction

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CACNA2D1HGNC:1399ENSG00000153956P54289Voltage-dependent calcium channel subunit alpha-2/delta-1clinvar
MIB1HGNC:21086ENSG00000101752Q86YT6E3 ubiquitin-protein ligase MIB1clinvar
KCNQ1HGNC:6294ENSG00000053918P51787Potassium voltage-gated channel subfamily KQT member 1clinvar
MYBPC3HGNC:7551ENSG00000134571Q14896Myosin-binding protein C, cardiac-typeclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CACNA2D1Voltage-dependent calcium channel subunit alpha-2/delta-1The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
MIB1E3 ubiquitin-protein ligase MIB1E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins.
KCNQ1Potassium voltage-gated channel subfamily KQT member 1Pore-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.
MYBPC3Myosin-binding protein C, cardiac-typeThick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.

Protein-family classification

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

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Ion channel127.9×0.142
Antibody/Immunoglobulin17.3×0.260
Transcription factor12.1×0.538
Other/Unknown10.5×0.962

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CACNA2D1Other/UnknownnoVWF_A, VWA_N, VDCC_a2/dsu
MIB1Transcription factornoZnf_ZZ, Znf_RING, Ankyrin_rpt
KCNQ1Ion channelyesK_chnl_volt-dep_KCNQ, Ion_trans_dom, K_chnl_volt-dep_KCQN1
MYBPC3Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, FN3_dom

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)4
unknown0

Top tissues across cohort

TissueCohort genes
biceps brachii1
skeletal muscle tissue of biceps brachii1
skeletal muscle tissue of rectus abdominis1
corpus epididymis1
kidney epithelium1
tibia1
left adrenal gland1
left adrenal gland cortex1
right adrenal gland cortex1
apex of heart1
cardiac atrium1
right atrium auricular region1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CACNA2D1261ubiquitousmarkerbiceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis
MIB1262ubiquitousmarkercorpus epididymis, kidney epithelium, tibia
KCNQ1132broadmarkerleft adrenal gland cortex, left adrenal gland, right adrenal gland cortex
MYBPC3149tissue_specificmarkerapex of heart, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KCNQ13,235
MIB12,280
CACNA2D12,002
MYBPC31,800

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CACNA2D1P5428930
KCNQ1P5178728
MYBPC3Q1489617
MIB1Q86YT66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

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

PathwayCohort genesFoldFDRSample cohort genes
Signaling by NOTCH1 HD Domain Mutants in Cancer1317.2×0.021MIB1
Phase 3 - rapid repolarisation1285.5×0.021KCNQ1
Constitutive Signaling by NOTCH1 HD Domain Mutants1190.3×0.021MIB1
Phase 2 - plateau phase1190.3×0.021KCNQ1
Signaling by NOTCH21178.4×0.021MIB1
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes1167.9×0.021CACNA2D1
Signaling by NOTCH31129.8×0.021MIB1
NOTCH3 Activation and Transmission of Signal to the Nucleus1119.0×0.021MIB1
NOTCH2 Activation and Transmission of Signal to the Nucleus1109.8×0.021MIB1
Signaling by NOTCH1 PEST Domain Mutants in Cancer1102.0×0.021MIB1
Signaling by NOTCH1 in Cancer1102.0×0.021MIB1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer1102.0×0.021MIB1
Signaling by NOTCH1189.2×0.021MIB1
Activated NOTCH1 Transmits Signal to the Nucleus189.2×0.021MIB1
Muscle contraction238.6×0.021KCNQ1, MYBPC3
Striated Muscle Contraction177.2×0.023MYBPC3
Cellular responses to mechanical stimuli164.9×0.025CACNA2D1
Voltage gated Potassium channels160.7×0.025KCNQ1
Constitutive Signaling by NOTCH1 PEST Domain Mutants149.2×0.028MIB1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants149.2×0.028MIB1
Signaling by NOTCH143.9×0.030MIB1
Potassium Channels133.6×0.037KCNQ1
Cardiac conduction127.2×0.044KCNQ1
Diseases of signal transduction by growth factor receptors and second messengers114.2×0.080MIB1
Neuronal System111.1×0.098KCNQ1
Cellular responses to stimuli17.9×0.131CACNA2D1
Disease13.3×0.283MIB1
Signal Transduction12.5×0.339MIB1

GO biological processes by enrichment

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

GO termCohort genesFoldFDRSample cohort genes
regulation of ventricular cardiac muscle cell membrane repolarization2421.3×6e-04CACNA2D1, KCNQ1
cardiac muscle contraction2200.6×0.001KCNQ1, MYBPC3
regulation of heart rate by cardiac conduction2187.2×0.001CACNA2D1, KCNQ1
gastrin-induced gastric acid secretion14213.0×0.004KCNQ1
negative regulation of voltage-gated potassium channel activity14213.0×0.004KCNQ1
rhythmic behavior12106.5×0.004KCNQ1
regulation of muscle filament sliding12106.5×0.004MYBPC3
corticosterone secretion12106.5×0.004KCNQ1
stomach development12106.5×0.004KCNQ1
regulation of gastric acid secretion11404.3×0.004KCNQ1
calcium ion transmembrane transport via high voltage-gated calcium channel11404.3×0.004CACNA2D1
membrane depolarization during bundle of His cell action potential11404.3×0.004CACNA2D1
regulation of membrane repolarization during action potential11404.3×0.004CACNA2D1
membrane repolarization during atrial cardiac muscle cell action potential1702.2×0.006KCNQ1
negative regulation of delayed rectifier potassium channel activity1702.2×0.006KCNQ1
iodide transport1601.9×0.006KCNQ1
regulation of atrial cardiac muscle cell membrane repolarization1601.9×0.006KCNQ1
neural tube formation1526.6×0.006MIB1
regulation of striated muscle contraction1526.6×0.006MYBPC3
positive regulation of cardiac muscle contraction1526.6×0.006KCNQ1
auditory receptor cell development1468.1×0.006KCNQ1
adrenergic receptor signaling pathway1468.1×0.006KCNQ1
intracellular chloride ion homeostasis1421.3×0.006KCNQ1
renal absorption1421.3×0.006KCNQ1
cardiac muscle cell contraction1421.3×0.006KCNQ1
membrane repolarization during action potential1421.3×0.006KCNQ1
membrane repolarization during cardiac muscle cell action potential1421.3×0.006KCNQ1
atrial cardiac muscle cell action potential1421.3×0.006KCNQ1
membrane repolarization during ventricular cardiac muscle cell action potential1421.3×0.006KCNQ1
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel1421.3×0.006CACNA2D1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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.

SymbolExample approved molecule
CACNA2D1PREGABALIN
KCNQ1AMBRISENTAN

Top cohort targets by molecule count

SymbolMoleculesMax phase
KCNQ1154
CACNA2D154
MIB100
MYBPC300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PREGABALIN4CACNA2D1
GABAPENTIN4CACNA2D1
NIMODIPINE4CACNA2D1
TACRINE4CACNA2D1
AMBRISENTAN4KCNQ1
DULOXETINE4KCNQ1
PALONOSETRON4KCNQ1
DARUNAVIR4KCNQ1
DARIFENACIN4KCNQ1
TOLTERODINE4KCNQ1
SOLIFENACIN4KCNQ1
EVEROLIMUS4KCNQ1
RALTEGRAVIR4KCNQ1
MARAVIROC4KCNQ1
ALVIMOPAN4KCNQ1
NEBIVOLOL4KCNQ1
SUNITINIB4KCNQ1
NELFINAVIR4KCNQ1
VOLINANSERIN3KCNQ1
Z1602CACNA2D1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
KCNQ1179Binding:96, Functional:64, ADMET:14, Toxicity:5
CACNA2D147Binding:45, ADMET:1, Toxicity:1

Cohort genes with high screening signal

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

SymbolChEMBL assays
KCNQ1179

Pharmacogenomics

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

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

Chemical tractability of cohort targets

20 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.

CompoundMax phaseCohort target (bioactivity)
PREGABALIN4CACNA2D1
GABAPENTIN4CACNA2D1
NIMODIPINE4CACNA2D1
TACRINE4CACNA2D1
AMBRISENTAN4KCNQ1
DULOXETINE4KCNQ1
PALONOSETRON4KCNQ1
DARUNAVIR4KCNQ1
DARIFENACIN4KCNQ1
TOLTERODINE4KCNQ1
SOLIFENACIN4KCNQ1
EVEROLIMUS4KCNQ1
RALTEGRAVIR4KCNQ1
MARAVIROC4KCNQ1
ALVIMOPAN4KCNQ1
NEBIVOLOL4KCNQ1
SUNITINIB4KCNQ1
NELFINAVIR4KCNQ1
VOLINANSERIN3KCNQ1
Z1602CACNA2D1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2CACNA2D1, KCNQ1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1MYBPC3
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1MIB1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
MIB10—
MYBPC30—

Clinical trials & evidence

Clinical trials

Clinical trials: 227.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified185
PHASE418
PHASE212
PHASE310
PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04704986PHASE4ACTIVE_NOT_RECRUITINGComparison of PolarX and the Arctic Front Cryoballoons for PVI in Patients With Symptomatic Paroxysmal AF
NCT05534581PHASE4ACTIVE_NOT_RECRUITINGSINGLE SHOT CHAMPION
NCT06168994PHASE4NOT_YET_RECRUITINGRole of Eplerenone in Reducing Recurrence of Atrial Fibrillation in Patient With Structural Heart Disease
NCT06765356PHASE4ACTIVE_NOT_RECRUITINGPragmatic Evaluation of a Pentaspline Pulsed Field Ablation System to Treat Atrial Fibrillation and Related Arrhythmias
NCT07487714PHASE4ENROLLING_BY_INVITATIONComparative Efficacy of 100-, 200-, & 400-mg Amiodarone in Patients With Paroxysmal AF Depending on Plasma Concentration
NCT00540787PHASE4COMPLETEDA Comparison of Antiarrhythmic Drug Therapy and Radio Frequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation
NCT00744874PHASE4COMPLETEDAblation of the Pulmonary Veins for Paroxysmal Afib
NCT00964392PHASE4COMPLETEDNAVISTAR® THERMOCOOL® Catheter Post Approval Registry
NCT01057394PHASE4TERMINATEDPost-Market Randomized Trial: Endoscopically- Guided Ablation vs. Radiofrequency Ablation
NCT01058980PHASE4COMPLETEDADenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination: the ADVICE Trial
NCT01070667PHASE4UNKNOWNDronedarone in Pacemakers Patients With Paroxysmal Atrial Fibrillation
NCT01504451PHASE4UNKNOWNLeft Atrial Ablation of Paroxysmal Atrial Fibrillation With Implantable Loop Recorder Follow Up Study: The LAAPITUP 2 Study
NCT01527279PHASE4COMPLETEDAntazoline in Rapid Cardioversion of Paroxysmal Atrial Fibrillation
NCT01645917PHASE4COMPLETEDDurability of Pulmonary Vein Isolation Following Cryoablation for Treatment of Paroxysmal Atrial Fibrillation
NCT01959425PHASE4TERMINATEDOral Anticoagulation Therapy Pilot Study
NCT02502110PHASE4UNKNOWNStudy of Statin for Reduction of Postoperative Paroxysmal Atrial Fibrillation
NCT03005366PHASE4COMPLETEDPredictive Factors to Effectively Terminate Paroxysmal Atrial Fibrillation by Blocking Atrial Selective Ionic Currents
NCT03624881PHASE4COMPLETEDEvaluation of VISITAG SURPOINT™ Module With External Processing Unit (EPU)
NCT00523978PHASE3COMPLETEDA Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation
NCT00741611PHASE3TERMINATEDStudy of HD Mesh Ablation System for Treatment of Paroxysmal Atrial Fibrillation
NCT00958165PHASE3COMPLETEDClinical Study of the CardioFocus Endoscopic Ablation System for the Treatment of Symptomatic AF
NCT01456000PHASE3COMPLETEDHeartLight Ablation in Patients With Paroxysmal Atrial Fibrillation (PAF)
NCT01611701PHASE3COMPLETEDCryoballoon Ablation of Pulmonary Veins After Failed RF Ablation in Patients With Paroxysmal AF
NCT01672346PHASE3UNKNOWNPV Reconnection After PVAI at Different Power Settings and Adenosine Provocation
NCT01867060PHASE3COMPLETEDUsing a Personal Heart Rhythm Monitor to Diagnose Paroxsymal Atrial Fibrillation in the Community
NCT01917981PHASE3WITHDRAWNTesting the Accuracy of a Personal Heart Rhythm Monitor to Detect Prolonged Paroxysmal Atrial Fibrillation
NCT02317068PHASE3COMPLETEDIncreasing Atrial Base Rate Pacing to Reduce Atrial Fibrillation
NCT05039359PHASE3TERMINATEDFlecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation
NCT00971204PHASE2COMPLETEDClinical Study of the CardioFocus Endoscopic Ablation System - Adaptive Contact (EAS-AC) for the Treatment of Symptomatic Atrial Fibrillation
NCT01185613PHASE2COMPLETEDClinical Evaluation of Therapy™ Cool Flex Ablation Catheter for the Treatment of Paroxysmal Atrial Fibrillation
NCT01353586PHASE2COMPLETEDREVOLUTION (WFCC-133) - Treatment of Paroxysmal Atrial Fibrillation
NCT01430949PHASE2COMPLETEDGENESIS Feasibility Study of the BARD Over-the-Wire Mesh Ablation System for the Treatment of Paroxysmal Atrial Fibrillation
NCT01709682PHASE2COMPLETEDA Comparison of the Drug Therapy Versus Re-Ablation
NCT01710852PHASE2COMPLETEDAntiarrhythmic and Symptomatic Effect of ISIS CRP Rx Targeting CRP in Paroxysmal Atrial Fibrillation
NCT01794416PHASE2COMPLETEDThoracoscopic Versus Endocardial Ablation in Patient With Paroxysmal AF After Failed Initial Endocardial Ablation
NCT01842529PHASE2COMPLETEDBotulinum Toxin Injection in Epicardial Fat Pads To Treat Atrial Fibrillation After Cardiac Surgery
NCT02002923PHASE2UNKNOWNPulmonary Vein Isolation Versus Botulinum Toxin Injection Plus Pulmonary Vein Isolation in Patients With Atrial Fibrillation
NCT02156076PHASE2TERMINATEDA Blinded Study to Evaluate Effect on Atrial Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation
NCT03539302PHASE2COMPLETEDINhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT)
NCT04609059PHASE2UNKNOWNFirst-in-Patient Study for Sing le Dose of M201-A Hydrochloride Injection in Japanese Patients With Paroxysmal Atrial Fibrillation

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
FLECAINIDE44
ANTAZOLINE43
ROSUVASTATIN42
ADENOSINE41
COLCHICINE41
DRONEDARONE41
EPLERENONE41
ONABOTULINUMTOXINA41
SODIUM CHLORIDE41
VERNAKALANT41
BMS-91937321
PILSICAINIDE21
CHEMBL135735601
CHEMBL60629801

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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This page pulls from 71 datasets indexed by BioBTree:

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