Episodic kinesigenic dyskinesia: genes and variants

Genes linked to Episodic kinesigenic dyskinesia

• PRRT2: Proline-rich transmembrane protein 2

  It modulates presynaptic neurotransmitter release and neuronal excitability through interactions with SNARE machinery and ion channels. Haploinsufficiency commonly causes paroxysmal kinesigenic dyskinesia, self-limited infantile seizures, or the combined infantile-convulsions-and-choreoathetosis phenotype.

  8 disease-causing and 243 uncertain variants in PRRT2 are linked to Episodic kinesigenic dyskinesia.

• 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 Episodic kinesigenic dyskinesia.

Weakly linked (only a few uncertain records): KCNJ10.

Where Episodic kinesigenic dyskinesia variants cluster

• PRRT2 Cytoplasmic (positions 290–317): 4 of 8 disease-causing changes, 6.1× more than its size predicts.
• PRRT2 Transmembrane (positions 318–338): 3 of 8 disease-causing changes, 6.1× more than its size predicts.

Known disease-causing variants in Episodic kinesigenic dyskinesia

Uncertain variants in Episodic kinesigenic dyskinesia that look disease-causing

Which prediction tools work for Episodic kinesigenic dyskinesia

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

• PolyPhen-2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Seizures, benign familial infantile, 3 is also caused by PRRT2 variants; they fall partly in the same places as the Episodic kinesigenic dyskinesia variants (3 disease-causing).
• Episodic ataxia type 2 is also caused by KCNA1 variants; they fall mostly in different places as the Episodic kinesigenic dyskinesia variants (27 disease-causing).

Diseases related to Episodic kinesigenic dyskinesia

• Seizures, benign familial infantile, 3, also linked to PRRT2
• Episodic ataxia type 2, also linked to KCNA1
• Generalized epilepsy-paroxysmal dyskinesia syndrome, also linked to KCNA1
• Benign familial infantile epilepsy, also linked to PRRT2

Frequently asked questions

Which genes are linked to Episodic kinesigenic dyskinesia?

In CATVariant, Episodic kinesigenic dyskinesia is linked to 2 analyzed proteins: PRRT2 (Proline-rich transmembrane protein 2) and KCNA1 (Potassium voltage-gated channel subfamily A member 1).

How many genetic variants are linked to Episodic kinesigenic dyskinesia?

301 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 244 are of uncertain significance or have conflicting reports.

Which uncertain variants in Episodic kinesigenic dyskinesia look disease-causing?

1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PRRT2 A306S. These are leads for expert review, not diagnoses.

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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