Generalized epilepsy-paroxysmal dyskinesia syndrome: genes and variants

Genes linked to Generalized epilepsy-paroxysmal dyskinesia syndrome

• KCNMA1: Calcium-activated potassium channel subunit alpha-1

  Its large-conductance potassium current couples membrane voltage and intracellular calcium to rapid repolarization in neurons, smooth muscle, and other excitable cells. Gain- and loss-of-function variants can cause paroxysmal dyskinesia, epilepsy, developmental impairment, and movement disorders.

  9 disease-causing and 352 uncertain variants in KCNMA1 are linked to Generalized epilepsy-paroxysmal dyskinesia syndrome.

• KCNA1: Potassium voltage-gated channel subfamily A member 1

  Its potassium current limits neuronal excitability and shapes action-potential repolarization, especially in axons and presynaptic terminals. Pathogenic variants classically cause episodic ataxia type 1 and can also produce epilepsy, myokymia, and related neurologic phenotypes.

  1 disease-causing and 0 uncertain variants in KCNA1 are linked to Generalized epilepsy-paroxysmal dyskinesia syndrome.

Where Generalized epilepsy-paroxysmal dyskinesia syndrome variants cluster

• KCNMA1 RCK N-terminal 2 (positions 839–983): 4 of 9 disease-causing changes, 3.8× more than its size predicts.

Known disease-causing variants in Generalized epilepsy-paroxysmal dyskinesia syndrome

Which prediction tools work for Generalized epilepsy-paroxysmal dyskinesia syndrome

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

• PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 69 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Liang-Wang syndrome is also caused by KCNMA1 variants; they fall mostly in different places as the Generalized epilepsy-paroxysmal dyskinesia syndrome variants (3 disease-causing).
• Episodic ataxia type 2 is also caused by KCNA1 variants; they fall mostly in different places as the Generalized epilepsy-paroxysmal dyskinesia syndrome variants (27 disease-causing).

Diseases related to Generalized epilepsy-paroxysmal dyskinesia syndrome

• Episodic ataxia type 2, also linked to KCNA1
• Epilepsy, idiopathic generalized, susceptibility to, 13, also linked to KCNMA1
• Idiopathic generalized epilepsy, also linked to KCNMA1
• Episodic kinesigenic dyskinesia, also linked to KCNA1
• Liang-Wang syndrome, also linked to KCNMA1
• Cerebellar atrophy, developmental delay, and seizures, also linked to KCNMA1

Frequently asked questions

Which genes are linked to Generalized epilepsy-paroxysmal dyskinesia syndrome?

In CATVariant, Generalized epilepsy-paroxysmal dyskinesia syndrome is linked to 2 analyzed proteins: KCNMA1 (Calcium-activated potassium channel subunit alpha-1) and KCNA1 (Potassium voltage-gated channel subfamily A member 1).

How many genetic variants are linked to Generalized epilepsy-paroxysmal dyskinesia syndrome?

374 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 352 are of uncertain significance or have conflicting reports.

Which uncertain variants in Generalized epilepsy-paroxysmal dyskinesia syndrome look disease-causing?

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

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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