Focal epilepsy: genes and variants

Genes linked to Focal epilepsy

• MECP2: Methyl-CpG-binding protein 2

  It interprets DNA methylation and organizes transcriptional and chromatin states that are especially important in mature neurons. Loss-of-function variants cause Rett syndrome, whereas increased dosage causes MECP2 duplication syndrome.

  2 disease-causing and 0 uncertain variants in MECP2 are linked to Focal epilepsy.

• CACNA1A: Voltage-dependent P/Q-type calcium channel subunit alpha-1A

  Its P/Q-type calcium current is a major trigger for neurotransmitter release at central synapses and is especially important in cerebellar circuits. Pathogenic variants cause a spectrum including familial hemiplegic migraine, episodic ataxia, spinocerebellar ataxia type 6, epilepsy, and developmental disorders.

  1 disease-causing and 0 uncertain variants in CACNA1A are linked to Focal epilepsy.

• SCN2A: Sodium channel protein type 2 subunit alpha

  The protein forms Nav1.2, a voltage-gated sodium channel that carries sodium current during neuronal action potentials. By shaping neuronal excitability and signal propagation, it supports brain circuits involved in development, learning, and seizure susceptibility.

  1 disease-causing and 0 uncertain variants in SCN2A are linked to Focal epilepsy.

• SCN10A: Sodium channel protein type 10 subunit alpha

  The protein forms Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channel found in excitable membranes. It helps generate sensory-neuron electrical signals and is especially important in mechanisms of neuropathic pain and inherited episodic pain.

  0 disease-causing and 0 uncertain variants in SCN10A are linked to Focal epilepsy.

• SCN1A: Sodium channel protein type 1 subunit alpha

  Its sodium current is especially important for reliable firing of inhibitory interneurons and therefore for balancing excitation across neural networks. Loss-of-function variants are the major cause of Dravet syndrome, while other variants cause GEFS+ or familial hemiplegic migraine.

  0 disease-causing and 0 uncertain variants in SCN1A are linked to Focal epilepsy.

• SCN4A: Sodium channel protein type 4 subunit alpha

  Its rapid sodium current initiates and propagates skeletal-muscle action potentials. Gain- and loss-of-function variants cause disorders of muscle excitability including sodium-channel myotonia, paramyotonia congenita, periodic paralysis, and some congenital myopathies.

  0 disease-causing and 0 uncertain variants in SCN4A are linked to Focal epilepsy.

• SCN9A: Sodium channel protein type 9 subunit alpha

  The protein forms Nav1.7, a voltage-gated sodium channel that amplifies electrical signals in peripheral sensory neurons. Changes in Nav1.7 activity can produce either excessive pain or congenital insensitivity to pain, making SCN9A central to pain biology.

  0 disease-causing and 0 uncertain variants in SCN9A are linked to Focal epilepsy.

Weakly linked (only a few uncertain records): DEPDC5, CDKL5 and GRIN2A.

Known disease-causing variants in Focal epilepsy

Same protein, different disease

• Rett syndrome is also caused by MECP2 variants; they fall mostly in different places as the Focal epilepsy variants (88 disease-causing).
• Severe neonatal-onset encephalopathy with microcephaly is also caused by MECP2 variants; they fall mostly in different places as the Focal epilepsy variants (29 disease-causing).
• X-linked intellectual disability-psychosis-macroorchidism syndrome is also caused by MECP2 variants; they fall mostly in different places as the Focal epilepsy variants (4 disease-causing).
• Episodic ataxia type 2 is also caused by CACNA1A variants; they fall mostly in different places as the Focal epilepsy variants (93 disease-causing).
• Spinocerebellar ataxia type 6 is also caused by CACNA1A variants; they fall mostly in different places as the Focal epilepsy variants (28 disease-causing).
• Migraine, familial hemiplegic, 1 is also caused by CACNA1A variants; they fall mostly in different places as the Focal epilepsy variants (26 disease-causing).
• CACNA1A-related complex neurodevelopmental disorder is also caused by CACNA1A variants; they fall mostly in different places as the Focal epilepsy variants (3 disease-causing).
• Seizures, benign familial infantile, 3 is also caused by SCN2A variants; they fall mostly in different places as the Focal epilepsy variants (167 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN2A variants; they fall mostly in different places as the Focal epilepsy variants (22 disease-causing).
• Episodic ataxia type 2 is also caused by SCN2A variants; they fall mostly in different places as the Focal epilepsy variants (15 disease-causing).
• West syndrome is also caused by SCN2A variants; they fall mostly in different places as the Focal epilepsy variants (11 disease-causing).
• Benign familial infantile epilepsy is also caused by SCN2A variants; they fall mostly in different places as the Focal epilepsy variants (6 disease-causing).

Diseases related to Focal epilepsy

• Epilepsy, also linked to CACNA1A, SCN10A, SCN1A, SCN2A and 2 more
• Amyotrophic lateral sclerosis, also linked to SCN10A, SCN1A, SCN2A, SCN4A and 1 more
• Cardiac arrhythmia, also linked to SCN10A, SCN1A, SCN2A, SCN4A and 1 more
• Lennox-Gastaut syndrome, also linked to SCN10A, SCN1A, SCN2A and SCN9A
• Episodic ataxia type 2, also linked to CACNA1A and SCN2A
• Generalized epilepsy with febrile seizures plus, also linked to SCN1A and SCN9A
• Migraine, familial hemiplegic, 1, also linked to CACNA1A and SCN1A
• Genetic developmental and epileptic encephalopathy, also linked to SCN1A and SCN2A
• Early-infantile DEE, also linked to SCN1A
• Severe myoclonic epilepsy in infancy, also linked to SCN1A
• Seizures, benign familial infantile, 3, also linked to SCN2A
• Rett syndrome, also linked to MECP2

Frequently asked questions

Which genes are linked to Focal epilepsy?

In CATVariant, Focal epilepsy is linked to 7 analyzed proteins: MECP2 (Methyl-CpG-binding protein 2), CACNA1A (Voltage-dependent P/Q-type calcium channel subunit alpha-1A), SCN2A (Sodium channel protein type 2 subunit alpha), SCN10A (Sodium channel protein type 10 subunit alpha), SCN1A (Sodium channel protein type 1 subunit alpha), SCN4A (Sodium channel protein type 4 subunit alpha) and 1 more.

How many genetic variants are linked to Focal epilepsy?

10 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 4 are of uncertain significance or have conflicting reports.

Which uncertain variants in Focal epilepsy 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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