Seizures, benign familial neonatal, 1: genes and variants

Genes linked to Seizures, benign familial neonatal, 1

• KCNQ2: Potassium voltage-gated channel subfamily KQT member 2

  Together with KCNQ3, its slowly activating potassium current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants cause a spectrum from self-limited familial neonatal epilepsy to severe developmental and epileptic encephalopathy.

  57 disease-causing and 28 uncertain variants in KCNQ2 are linked to Seizures, benign familial neonatal, 1.

• KCNQ3: Potassium voltage-gated channel subfamily KQT member 3

  Together with KCNQ2, its slowly activating current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants can cause self-limited neonatal epilepsy or more severe developmental and epileptic encephalopathy.

  7 disease-causing and 43 uncertain variants in KCNQ3 are linked to Seizures, benign familial neonatal, 1.

Where Seizures, benign familial neonatal, 1 variants cluster

• KCNQ2 Mediates interaction with SLC5A3/SMIT1 (positions 222–323): 20 of 57 disease-causing changes, 3.0× more than its size predicts.
• KCNQ2 Segment S4 (positions 197–215): 8 of 57 disease-causing changes, 6.4× more than its size predicts.
• KCNQ2 Extracellular (positions 184–196): 5 of 57 disease-causing changes, 5.9× more than its size predicts.
• KCNQ2 Cytoplasmic (positions 216–227): 3 of 57 disease-causing changes, 3.8× more than its size predicts.
• KCNQ3 Mediates interaction with calmodulin (positions 356–537): 3 of 7 disease-causing changes, 2.0× more than its size predicts.

Known disease-causing variants in Seizures, benign familial neonatal, 1

Showing 60 of 64.

Which prediction tools work for Seizures, benign familial neonatal, 1

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

• REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 94 out of 100
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 88 out of 100
• phyloP: 76 out of 100

Same protein, different disease

• Early-infantile DEE is also caused by KCNQ2 variants; they fall partly in the same places as the Seizures, benign familial neonatal, 1 variants (199 disease-causing).
• Benign neonatal seizures is also caused by KCNQ3 variants; they fall partly in the same places as the Seizures, benign familial neonatal, 1 variants (13 disease-causing).

Diseases related to Seizures, benign familial neonatal, 1

• Epilepsy, also linked to KCNQ2 and KCNQ3
• Early-infantile DEE, also linked to KCNQ2
• Seizures, benign familial infantile, 3, also linked to KCNQ3
• West syndrome, also linked to KCNQ2
• Benign neonatal seizures, also linked to KCNQ3
• Self-limited epilepsy with centrotemporal spikes, also linked to KCNQ3
• Paediatric disorders, also linked to KCNQ2
• Autosomal dominant epilepsy, also linked to KCNQ2
• Genetic developmental and epileptic encephalopathy, also linked to KCNQ2

Frequently asked questions

Which genes are linked to Seizures, benign familial neonatal, 1?

In CATVariant, Seizures, benign familial neonatal, 1 is linked to 2 analyzed proteins: KCNQ2 (Potassium voltage-gated channel subfamily KQT member 2) and KCNQ3 (Potassium voltage-gated channel subfamily KQT member 3).

How many genetic variants are linked to Seizures, benign familial neonatal, 1?

157 variants: 64 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 71 are of uncertain significance or have conflicting reports.

Which uncertain variants in Seizures, benign familial neonatal, 1 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 Seizures, benign familial neonatal, 1?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 24 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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