Familial atrial fibrillation: genes and variants
Explore variant evidence for Familial atrial fibrillation across 6 analyzed proteins (KCNQ1, GJA5, SCN5A, KCNJ2, NPPA and 1 more). Linked ClinVar records include 17 pathogenic or likely pathogenic variants, 279 variants of uncertain significance and 27 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Familial atrial fibrillation
KCNQ1: Potassium voltage-gated channel subfamily KQT member 1
The protein forms the pore of a voltage-gated potassium channel that helps set electrical activity in heart muscle. Its partnerships with KCNE subunits also support normal function in the inner ear and other tissues, while KCNQ1 variants are linked to long-QT and short-QT syndromes.
8 ClinVar pathogenic / likely pathogenic and 18 uncertain variants in KCNQ1 have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
GJA5: Gap junction alpha-5 protein
It forms connexin 40 gap junctions that support rapid electrical coupling in atrial myocardium and the cardiac conduction system. Pathogenic variants can predispose to atrial fibrillation and conduction disease, and altered expression can disrupt coordinated cardiac impulse propagation.
3 ClinVar pathogenic / likely pathogenic and 152 uncertain variants in GJA5 have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
SCN5A: Sodium channel protein type 5 subunit alpha
Its rapid inward sodium current drives the upstroke of the cardiac action potential and enables fast electrical conduction through atrial, ventricular, and conduction-system tissue. Pathogenic variants can cause long-QT syndrome type 3, Brugada syndrome, conduction disease, and overlapping arrhythmia phenotypes.
3 ClinVar pathogenic / likely pathogenic and 28 uncertain variants in SCN5A have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
KCNJ2: Inward rectifier potassium channel 2
Its inward-rectifier current stabilizes the resting membrane potential in cardiac and skeletal muscle and contributes to terminal cardiac repolarization. Loss-of-function variants cause Andersen-Tawil syndrome, while gain-of-function variants can cause short-QT syndrome.
3 ClinVar pathogenic / likely pathogenic and 14 uncertain variants in KCNJ2 have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
NPPA: Natriuretic peptides A
It is processed to atrial natriuretic peptide, which promotes natriuresis, vasodilation, and suppression of the renin-angiotensin-aldosterone system in response to cardiac stretch. Pathogenic variants can cause familial atrial fibrillation or rare atrial cardiomyopathy phenotypes.
0 ClinVar pathogenic / likely pathogenic and 74 uncertain variants in NPPA have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
ABCC9: ATP-binding cassette sub-family C member 9
A regulatory subunit of ATP-sensitive potassium (KATP) channels, partnering with KCNJ11 or KCNJ8 to control channel activation. It is a multi-pass membrane protein with important roles in cardiac and smooth-muscle excitability, and altered ABCC9 function is associated with cardiomyopathy, atrial fibrillation, and neurodevelopmental syndromes.
0 ClinVar pathogenic / likely pathogenic and 20 uncertain variants in ABCC9 have source records linked to Familial atrial fibrillation. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Familial atrial fibrillation
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| KCNJ2 R218W | 218 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNJ2 R218L | 218 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ1 G179S | 179 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ1 R190W | 190 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| KCNQ1 R231H | 231 | Segment S4 | Pathogenic / likely pathogenic (★★) |
| KCNQ1 G269S | 269 | Segment S5 | Pathogenic / likely pathogenic (★★) |
| KCNQ1 R562S | 562 | Interaction with KCNE1 C-terminus | Pathogenic / likely pathogenic (★★) |
| KCNQ1 G272D | 272 | Segment S5 | Pathogenic / likely pathogenic (★★) |
| KCNQ1 R594Q | 594 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SCN5A G1408R | 1408 | III | Pathogenic / likely pathogenic (★★) |
| SCN5A D1595N | 1595 | IV | Pathogenic / likely pathogenic (★★) |
| SCN5A G1743R | 1743 | IV | Pathogenic / likely pathogenic (★★) |
| KCNJ2 E299G | 299 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| GJA5 V85I | 85 | Transmembrane | Pathogenic / likely pathogenic |
| GJA5 L221I | 221 | Transmembrane | Pathogenic / likely pathogenic |
| GJA5 L229M | 229 | Cytoplasmic | Pathogenic / likely pathogenic |
| KCNQ1 S140G | 140 | Segment S1 | Pathogenic / likely pathogenic |
Which prediction tools work for Familial atrial fibrillation
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 100 out of 100
- PolyPhen-2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- ESM1b (LLR): 98 out of 100
- SIFT: 96 out of 100
Same protein, different disease
- Long QT syndrome also has ClinVar records linked to KCNQ1 variants; they fall mostly in different places as the Familial atrial fibrillation variants (175 pathogenic / likely pathogenic).
- Cardiac arrhythmia also has ClinVar records linked to KCNQ1 variants; they fall mostly in different places as the Familial atrial fibrillation variants (49 pathogenic / likely pathogenic).
- Jervell and Lange-Nielsen syndrome also has ClinVar records linked to KCNQ1 variants; they fall mostly in different places as the Familial atrial fibrillation variants (4 pathogenic / likely pathogenic).
- Short QT syndrome type 3 also has ClinVar records linked to KCNQ1 variants; they fall mostly in different places as the Familial atrial fibrillation variants (4 pathogenic / likely pathogenic).
- Brugada syndrome also has ClinVar records linked to SCN5A variants; they fall mostly in different places as the Familial atrial fibrillation variants (24 pathogenic / likely pathogenic).
- Cardiac arrhythmia also has ClinVar records linked to SCN5A variants; they fall mostly in different places as the Familial atrial fibrillation variants (17 pathogenic / likely pathogenic).
- Long QT syndrome also has ClinVar records linked to SCN5A variants; they fall mostly in different places as the Familial atrial fibrillation variants (16 pathogenic / likely pathogenic).
- Dilated cardiomyopathy also has ClinVar records linked to SCN5A variants; they fall mostly in different places as the Familial atrial fibrillation variants (4 pathogenic / likely pathogenic).
- Progressive familial heart block also has ClinVar records linked to SCN5A variants; they fall mostly in different places as the Familial atrial fibrillation variants (4 pathogenic / likely pathogenic).
- Andersen Tawil syndrome also has ClinVar records linked to KCNJ2 variants; they fall mostly in different places as the Familial atrial fibrillation variants (34 pathogenic / likely pathogenic).
- Short QT syndrome type 3 also has ClinVar records linked to KCNJ2 variants; they fall mostly in different places as the Familial atrial fibrillation variants (28 pathogenic / likely pathogenic).
Diseases related to Familial atrial fibrillation
- Long QT syndrome, also linked to KCNJ2, KCNQ1 and SCN5A
- Cardiac arrhythmia, also linked to KCNJ2, KCNQ1 and SCN5A
- Dilated cardiomyopathy, also linked to ABCC9 and SCN5A
- Short QT syndrome type 3, also linked to KCNJ2 and KCNQ1
- Epilepsy, also linked to KCNQ1 and SCN5A
- Cardiomyopathy, also linked to ABCC9
- Primary dilated cardiomyopathy, also linked to SCN5A
- Type 2 diabetes mellitus, also linked to KCNQ1
- Brugada syndrome, also linked to SCN5A
- Diabetes, also linked to KCNQ1
- Andersen Tawil syndrome, also linked to KCNJ2
- Monogenic hearing loss, also linked to KCNQ1
Frequently asked questions
Which genes have records linked to Familial atrial fibrillation?
This view contains 6 analyzed proteins: KCNQ1, GJA5, SCN5A, KCNJ2, NPPA and 1 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 17 pathogenic or likely pathogenic variants, 279 variants of uncertain significance and 27 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 353 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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