Atrial fibrillation, familial, 10: genes and variants

Genes linked to Atrial fibrillation, familial, 10

• 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 disease-causing and 18 uncertain variants in KCNQ1 are linked to Atrial fibrillation, familial, 10.

• 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 disease-causing and 28 uncertain variants in SCN5A are linked to Atrial fibrillation, familial, 10.

• 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 disease-causing and 14 uncertain variants in KCNJ2 are linked to Atrial fibrillation, familial, 10.

• 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 disease-causing and 20 uncertain variants in ABCC9 are linked to Atrial fibrillation, familial, 10.

• 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 disease-causing and 152 uncertain variants in GJA5 are linked to Atrial fibrillation, familial, 10.

• 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 disease-causing and 74 uncertain variants in NPPA are linked to Atrial fibrillation, familial, 10.

Known disease-causing variants in Atrial fibrillation, familial, 10

Which prediction tools work for Atrial fibrillation, familial, 10

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• 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 is also caused by KCNQ1 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (175 disease-causing).
• Cardiac arrhythmia is also caused by KCNQ1 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (49 disease-causing).
• Jervell and Lange-Nielsen syndrome is also caused by KCNQ1 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (4 disease-causing).
• Short QT syndrome type 3 is also caused by KCNQ1 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (4 disease-causing).
• Brugada syndrome is also caused by SCN5A variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (24 disease-causing).
• Cardiac arrhythmia is also caused by SCN5A variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (17 disease-causing).
• Long QT syndrome is also caused by SCN5A variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (16 disease-causing).
• Dilated cardiomyopathy is also caused by SCN5A variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (4 disease-causing).
• Progressive familial heart block is also caused by SCN5A variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (4 disease-causing).
• Andersen Tawil syndrome is also caused by KCNJ2 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (34 disease-causing).
• Short QT syndrome type 3 is also caused by KCNJ2 variants; they fall mostly in different places as the Atrial fibrillation, familial, 10 variants (28 disease-causing).

Diseases related to Atrial fibrillation, familial, 10

• 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
• Primary dilated cardiomyopathy, also linked to SCN5A
• Type 2 diabetes mellitus, also linked to KCNQ1
• Brugada syndrome, also linked to SCN5A
• Andersen Tawil syndrome, also linked to KCNJ2
• Monogenic hearing loss, also linked to KCNQ1
• Hypertrichotic osteochondrodysplasia Cantu type, also linked to ABCC9
• Diabetes mellitus, also linked to KCNQ1

Frequently asked questions

Which genes are linked to Atrial fibrillation, familial, 10?

In CATVariant, Atrial fibrillation, familial, 10 is linked to 6 analyzed proteins: KCNQ1 (Potassium voltage-gated channel subfamily KQT member 1), SCN5A (Sodium channel protein type 5 subunit alpha), KCNJ2 (Inward rectifier potassium channel 2), ABCC9 (ATP-binding cassette sub-family C member 9), GJA5 (Gap junction alpha-5 protein) and NPPA (Natriuretic peptides A).

How many genetic variants are linked to Atrial fibrillation, familial, 10?

339 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 306 are of uncertain significance or have conflicting reports.

Which uncertain variants in Atrial fibrillation, familial, 10 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Atrial fibrillation, familial, 10?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 14 disease-causing and 30 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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