Rolandic epilepsy: genes and variants

Genes linked to Rolandic epilepsy

• RELN: Reelin

  It is secreted during brain development to guide neuronal migration and cortical layering and later modulates synaptic plasticity. Biallelic loss-of-function variants cause lissencephaly with cerebellar hypoplasia, while heterozygous variants can be associated with epilepsy.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in RELN have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• GRIN2A: Glutamate receptor ionotropic, NMDA 2A

  It helps determine the kinetics and signaling properties of NMDA receptors, particularly in cortical circuits involved in language and epilepsy. Pathogenic variants cause a spectrum of developmental epileptic encephalopathies and epilepsy-aphasia disorders.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN2A have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• GABRG2: Gamma-aminobutyric acid receptor subunit gamma-2

  The gene product supplies the gamma-2 subunit of synaptic GABA-A receptors, which are pentameric chloride channels activated by the inhibitory neurotransmitter GABA. The subunit helps receptor assembly and localization at neuronal membranes, and GABRG2 variants are associated with several epilepsy syndromes.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GABRG2 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• CHD2: ATP-dependent chromatin remodeler CHD2

  It remodels chromatin to regulate transcription and is particularly important for neuronal development and activity-dependent gene expression. Haploinsufficiency commonly causes developmental and epileptic encephalopathy, often with photosensitive seizures and intellectual disability.

  2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CHD2 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• 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.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KCNQ3 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• GRIN1: Glutamate receptor ionotropic, NMDA 1

  It provides an obligatory subunit of NMDA receptors and is essential for glutamate-dependent synaptic transmission, calcium signaling, and plasticity. Pathogenic variants can cause GRIN1-related neurodevelopmental disorder with intellectual disability, movement abnormalities, epilepsy, and cortical visual impairment.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN1 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN2A have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• SLC2A1: Solute carrier family 2, facilitated glucose transporter member 1

  It provides basal glucose uptake in many tissues and is the principal route for glucose entry across the blood-brain barrier. Haploinsufficiency causes GLUT1 deficiency syndrome with epilepsy, developmental impairment, and movement disorders from inadequate brain glucose delivery.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SLC2A1 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

• CNTNAP2: Contactin-associated protein-like 2

  It organizes specialized neuronal membrane domains and contributes to axonal development, synaptic connectivity, and clustering of potassium channels at juxtaparanodes. Biallelic loss-of-function variants can cause severe neurodevelopmental disease with epilepsy and language impairment, while heterozygous associations are more complex.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CNTNAP2 have source records linked to Rolandic epilepsy. Association strength is not clinical gene validity.

Weakly linked (only a few uncertain records): DEPDC5, WWOX, KCNQ2, KCNT1, PCDH19 and SLC6A1.

ClinVar pathogenic and likely pathogenic variants linked to Rolandic epilepsy

Which prediction tools work for Rolandic epilepsy

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• PolyPhen-2: 60 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Familial temporal lobe epilepsy 7 also has ClinVar records linked to RELN variants; they fall mostly in different places as the Rolandic epilepsy variants (4 pathogenic / likely pathogenic).
• Landau-Kleffner syndrome also has ClinVar records linked to GRIN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (85 pathogenic / likely pathogenic).
• Benign neonatal seizures also has ClinVar records linked to KCNQ3 variants; they fall mostly in different places as the Rolandic epilepsy variants (13 pathogenic / likely pathogenic).
• Seizures, benign familial infantile, 3 also has ClinVar records linked to KCNQ3 variants; they fall mostly in different places as the Rolandic epilepsy variants (8 pathogenic / likely pathogenic).
• Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant also has ClinVar records linked to GRIN1 variants; they fall mostly in different places as the Rolandic epilepsy variants (55 pathogenic / likely pathogenic).
• Seizures, benign familial infantile, 3 also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (167 pathogenic / likely pathogenic).
• Complex neurodevelopmental disorder also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (22 pathogenic / likely pathogenic).
• Episodic ataxia type 2 also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (15 pathogenic / likely pathogenic).
• Infantile spasms also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (14 pathogenic / likely pathogenic).
• Benign familial infantile epilepsy also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Rolandic epilepsy variants (6 pathogenic / likely pathogenic).

Diseases related to Rolandic epilepsy

• Epilepsy, also linked to GABRG2, GRIN2A, KCNQ3 and SCN2A
• Seizures, benign familial infantile, 3, also linked to KCNQ3 and SCN2A
• Complex neurodevelopmental disorder, also linked to CHD2 and SCN2A
• Migraine, also linked to GABRG2 and SCN2A
• Genetic developmental and epileptic encephalopathy, also linked to GABRG2 and SCN2A
• Lennox-Gastaut syndrome, also linked to GABRG2 and SCN2A
• Amyotrophic lateral sclerosis, also linked to SCN2A
• Episodic ataxia type 2, also linked to SCN2A
• Alzheimer disease, also linked to GRIN2A
• Generalized epilepsy with febrile seizures plus, also linked to GABRG2
• Landau-Kleffner syndrome, also linked to GRIN2A
• Cardiac arrhythmia, also linked to SCN2A

Frequently asked questions

Which genes have records linked to Rolandic epilepsy?

This view contains 9 analyzed proteins: RELN, GRIN2A, GABRG2, CHD2, KCNQ3 and 4 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 8 pathogenic or likely pathogenic variants, 0 variants of uncertain significance and 0 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 34 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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