EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2: genes and variants

Genes linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2

• GABRB3: Gamma-aminobutyric acid receptor subunit beta-3

  It contributes to inhibitory GABA-A receptor currents in the brain and is particularly important during neurodevelopment. Pathogenic variants can cause developmental and epileptic encephalopathy, while altered dosage within chromosome 15q11-q13 contributes to neurodevelopmental disorders.

  33 disease-causing and 180 uncertain variants in GABRB3 are linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2.

• 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.

  28 disease-causing and 201 uncertain variants in GABRG2 are linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2.

• GABRA1: Gamma-aminobutyric acid receptor subunit alpha-1

  The gene product supplies the alpha-1 subunit of a pentameric GABA-A receptor, a ligand-gated chloride channel in the brain. GABA binding allows chloride influx that dampens neuronal activity, making this receptor important for inhibition and seizure biology.

  19 disease-causing and 151 uncertain variants in GABRA1 are linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2.

Where EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 variants cluster

• GABRG2 Extracellular (positions 323–334): 5 of 28 disease-causing changes, 7.1× more than its size predicts.
• GABRG2 Transmembrane (positions 303–322): 6 of 28 disease-causing changes, 5.1× more than its size predicts.
• GABRA1 Transmembrane (positions 280–301): 5 of 19 disease-causing changes, 5.5× more than its size predicts.
• GABRB3 Extracellular (positions 293–304): 4 of 33 disease-causing changes, 4.8× more than its size predicts.
• GABRB3 Transmembrane (positions 247–267): 5 of 33 disease-causing changes, 3.4× more than its size predicts.

Known disease-causing variants in EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2

Showing 60 of 80.

Uncertain variants in EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 that look disease-causing

Which prediction tools work for EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2

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

• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 85 out of 100
• CADD: 81 out of 100
• phyloP: 65 out of 100

Same protein, different disease

• Epilepsy, idiopathic generalized, susceptibility to, 13 is also caused by GABRA1 variants; they fall partly in the same places as the EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 variants (24 disease-causing).

Diseases related to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2

• Epilepsy, also linked to GABRA1, GABRB3 and GABRG2
• Lennox-Gastaut syndrome, also linked to GABRA1, GABRB3 and GABRG2
• Generalized epilepsy with febrile seizures plus, also linked to GABRG2
• Epilepsy, idiopathic generalized, susceptibility to, 13, also linked to GABRA1
• Febrile seizures, familial, 3a, also linked to GABRG2
• Idiopathic generalized epilepsy, also linked to GABRA1
• Self-limited epilepsy with centrotemporal spikes, also linked to GABRG2
• Familial sleep-related hypermotor epilepsy, also linked to GABRG2
• Genetic developmental and epileptic encephalopathy, also linked to GABRG2

Frequently asked questions

Which genes are linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2?

In CATVariant, EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 is linked to 3 analyzed proteins: GABRB3 (Gamma-aminobutyric acid receptor subunit beta-3), GABRG2 (Gamma-aminobutyric acid receptor subunit gamma-2) and GABRA1 (Gamma-aminobutyric acid receptor subunit alpha-1).

How many genetic variants are linked to EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2?

649 variants: 80 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 532 are of uncertain significance or have conflicting reports.

Which uncertain variants in EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 look disease-causing?

10 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example GABRG2 P83T, GABRB3 T288A, GABRB3 K127R, GABRA1 R214S and GABRB3 K304E. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.85, based on 72 disease-causing and 44 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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