Summary
Childhood absence epilepsy (MONDO:0010826) is a disease with 9 cohort genes (4 GWAS associations across 2 studies) and 11 clinical trials. Top therapeutic interventions include brivaracetam, cannabidiol, and ethosuximide.
At a glance
- Prevalence: 1-9 / 100 000 (United States) [Orphanet-validated]
- Cohort genes: 9
- GWAS associations: 4
- ClinVar variants: 23
- Phenotypes (HPO): 21
- Clinical trials: 11
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|
| Annual incidence | 1-9 / 100 000 | 5 | United States | Validated |
Signs & symptoms
Clinical features (HPO)
21 HPO clinical features (Orphanet curated; top 21 by frequency):
| HPO ID | Term | Frequency |
|---|
| HP:0010848 | EEG with spike-wave complexes (2.5-3.5 Hz) | Very frequent (80-99%) |
| HP:0011147 | Typical absence seizure | Very frequent (80-99%) |
| HP:0000980 | Pallor | Frequent (30-79%) |
| HP:0007018 | Attention deficit hyperactivity disorder | Frequent (30-79%) |
| HP:0000716 | Depression | Occasional (5-29%) |
| HP:0000739 | Anxiety | Occasional (5-29%) |
| HP:0001249 | Intellectual disability | Occasional (5-29%) |
| HP:0001328 | Specific learning disability | Occasional (5-29%) |
| HP:0002069 | Bilateral tonic-clonic seizure | Occasional (5-29%) |
| HP:0002373 | Febrile seizure (within the age range of 3 months to 6 years) | Occasional (5-29%) |
| HP:0002883 | Hyperventilation | Occasional (5-29%) |
| HP:0007738 | Uncontrolled eye movements | Occasional (5-29%) |
| HP:0010522 | Dyslexia | Occasional (5-29%) |
| HP:0010794 | Impaired visuospatial constructive cognition | Occasional (5-29%) |
| HP:0011150 | Myoclonic absence | Occasional (5-29%) |
| HP:0012433 | Abnormal social behavior | Occasional (5-29%) |
| HP:0030218 | Punding | Occasional (5-29%) |
| HP:0031469 | Low self esteem | Occasional (5-29%) |
| HP:0000020 | Urinary incontinence | Very rare (<1-4%) |
| HP:0006961 | Jerky head movements | Very rare (<1-4%) |
| HP:0045084 | Limb myoclonus | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|
| Canonical name | childhood absence epilepsy |
| Mondo ID | MONDO:0010826 |
| OMIM | 600131 |
| Orphanet | 64280 |
| DOID | DOID:0050708, DOID:1825 |
| ICD-11 | 726403046 |
| SNOMED CT | 50866000 |
| UMLS | C4281785 |
| MedGen | 924120 |
| GARD | 0016667 |
| Is cancer (heuristic) | no |
Also known as: pyknolepsy
Data availability: 23 ClinVar variants · 4 GWAS associations (2 studies) · 3 GenCC gene-disease records · 13 cell lines.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › hereditary generalized epilepsy › idiopathic generalized epilepsy › childhood-onset idiopathic generalized epilepsy syndrome › childhood absence epilepsy
Subtypes (1): febrile seizures, familial, 8
Genetics & variants
GWAS landscape
4 GWAS associations across 2 studies. Top hits map to 1 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|
| rs12185644 | 1e-12 | ACTG1P22 - VRK2 | A | |
| rs13020210 | 2e-08 | LINC01412 | G | 5.58 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|
| GCST90271616 | International League Against Epilepsy Consortium on Complex Epilepsies | 2023 | 1,049 | 42,436 | GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture. |
| GCST007345 | International League Against Epilepsy Consortium on Complex Epilepsies | 2018 | 778 | 24,218 | Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 2 |
MAF distribution
| Bucket | Variants |
|---|
| common (>=0.05) | 2 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|
| intron_variant | 2 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|
| rs12185644 | 2 | 57824634 | C>A,G,T | 0.05 | intron_variant | ACTG1P22 - VRK2 | 1e-12 | Tier 4: intronic/intergenic |
| rs13020210 | 2 | 144623658 | G>A,C | 0.2 | intron_variant | LINC01412 | 2e-08 | Tier 4: intronic/intergenic |
ClinVar germline variants
23 retrieved; paginated sample, class counts are floors:
11 benign, 7 likely benign, 4 uncertain significance, 1 not provided
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|
| 477864 | NM_000811.3(GABRA6):c.371C>G (p.Ser124Cys) | GABRA6 | Uncertain significance | criteria provided, single submitter |
| 477870 | NM_000811.3(GABRA6):c.847A>G (p.Met283Val) | GABRA6 | Uncertain significance | criteria provided, single submitter |
| 644592 | NM_000811.3(GABRA6):c.255G>C (p.Gln85His) | GABRA6 | Uncertain significance | criteria provided, single submitter |
| 637055 | NM_001037.5(SCN1B):c.85G>A (p.Glu29Lys) | SCN1B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1154309 | NM_000811.3(GABRA6):c.1142T>C (p.Ile381Thr) | GABRA6 | Likely benign | criteria provided, single submitter |
| 1168450 | NM_000811.3(GABRA6):c.1210C>T (p.Pro404Ser) | GABRA6 | Benign | criteria provided, single submitter |
| 1169909 | NM_000811.3(GABRA6):c.9G>A (p.Ser3=) | GABRA6 | Benign | criteria provided, single submitter |
| 1169910 | NM_000811.3(GABRA6):c.951G>T (p.Ala317=) | GABRA6 | Benign | criteria provided, single submitter |
| 1169911 | NM_000811.3(GABRA6):c.1005C>G (p.Ala335=) | GABRA6 | Benign | criteria provided, single submitter |
| 1169912 | NM_000811.3(GABRA6):c.1344C>G (p.Val448=) | GABRA6 | Benign | criteria provided, single submitter |
| 1169913 | NM_000811.3(GABRA6):c.*135C>T | GABRA6 | Benign | criteria provided, single submitter |
| 477861 | NM_000811.3(GABRA6):c.1053A>C (p.Lys351Asn) | GABRA6 | Likely benign | criteria provided, single submitter |
| 477862 | NM_000811.3(GABRA6):c.1156G>A (p.Glu386Lys) | GABRA6 | Likely benign | criteria provided, single submitter |
| 477863 | NM_000811.3(GABRA6):c.339G>A (p.Thr113=) | GABRA6 | Likely benign | criteria provided, single submitter |
| 477865 | NM_000811.3(GABRA6):c.507T>C (p.Ala169=) | GABRA6 | Likely benign | criteria provided, single submitter |
| 477866 | NM_000811.3(GABRA6):c.560C>T (p.Thr187Met) | GABRA6 | Benign | criteria provided, single submitter |
| 477867 | NM_000811.3(GABRA6):c.639A>G (p.Gln213=) | GABRA6 | Benign | criteria provided, single submitter |
| 477868 | NM_000811.3(GABRA6):c.663A>G (p.Lys221=) | GABRA6 | Likely benign | criteria provided, single submitter |
| 477869 | NM_000811.3(GABRA6):c.710A>G (p.Gln237Arg) | GABRA6 | Likely benign | criteria provided, multiple submitters, no conflicts |
| 707554 | NM_000811.3(GABRA6):c.805G>A (p.Val269Ile) | GABRA6 | Benign | criteria provided, single submitter |
| 715115 | NM_000811.3(GABRA6):c.60A>G (p.Lys20=) | GABRA6 | Benign | criteria provided, single submitter |
| 767175 | NM_000811.3(GABRA6):c.594C>A (p.Val198=) | GABRA6 | Benign | criteria provided, single submitter |
| 4279940 | GRCh37/hg19 15q11.2-12(chr15:25582396-27018223)x1 | ATP10A | not provided | no classification provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 26 · Orphanet: 24 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|
| GABRB3 | Definitive | Autosomal dominant | epilepsy, childhood absence, susceptibility to, 5 | 8 |
| SLC2A1 | Strong | Autosomal dominant | childhood onset GLUT1 deficiency syndrome 2 | 14 |
| CACNA1H | Supportive | Autosomal dominant | childhood absence epilepsy | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|
| SLC2A1 | Orphanet:168577 | Hereditary cryohydrocytosis with reduced stomatin |
| SLC2A1 | Orphanet:1942 | Epilepsy with myoclonic-atonic seizures |
| SLC2A1 | Orphanet:2131 | Alternating hemiplegia of childhood |
| SLC2A1 | Orphanet:53583 | Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity |
| SLC2A1 | Orphanet:71277 | Classic glucose transporter type 1 deficiency syndrome |
| SLC2A1 | Orphanet:86911 | Epilepsy with myoclonic absences |
| SLC2A1 | Orphanet:98811 | Paroxysmal exertion-induced dyskinesia |
| CACNA1H | Orphanet:642671 | Familial hyperaldosteronism type IV |
| CACNA1H | Orphanet:64280 | Childhood absence epilepsy |
| GABRB3 | Orphanet:2382 | Lennox-Gastaut syndrome |
| GABRB3 | Orphanet:64280 | Childhood absence epilepsy |
| SCN1B | Orphanet:130 | Brugada syndrome |
| SCN1B | Orphanet:1934 | Early infantile developmental and epileptic encephalopathy |
| SCN1B | Orphanet:33069 | Dravet syndrome |
| SCN1B | Orphanet:334 | Hereditary atrial fibrillation |
| SCN1B | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| SCN1B | Orphanet:871 | Hereditary progressive cardiac conduction defect |
| BCL11A | Orphanet:251380 | Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome |
| BCL11A | Orphanet:619233 | Hereditary persistence of fetal hemoglobin-intellectual disability syndrome |
| ATP10A | Orphanet:411515 | Angelman syndrome due to imprinting defect in 15q11-q13 |
| ZEB2 | Orphanet:261537 | Mowat-Wilson syndrome due to monosomy 2q22 |
| ZEB2 | Orphanet:261552 | Mowat-Wilson syndrome due to a ZEB2 point mutation |
| ZEB2 | Orphanet:626 | Large/giant congenital melanocytic nevus |
| FANCL | Orphanet:84 | Fanconi anemia |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|
| gwas_only | 3 |
| multi_evidence | 6 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|
| SLC2A1 | HGNC:11005 | ENSG00000117394 | P11166 | Solute carrier family 2, facilitated glucose transporter member 1 | gencc |
| CACNA1H | HGNC:1395 | ENSG00000196557 | O95180 | Voltage-dependent T-type calcium channel subunit alpha-1H | gencc |
| GABRB3 | HGNC:4083 | ENSG00000166206 | P28472 | Gamma-aminobutyric acid receptor subunit beta-3 | gencc |
| SCN1B | HGNC:10586 | ENSG00000105711 | Q07699 | Sodium channel regulatory subunit beta-1 | clinvar |
| BCL11A | HGNC:13221 | ENSG00000119866 | Q9H165 | BCL11 transcription factor A | gwas |
| ATP10A | HGNC:13542 | ENSG00000206190 | O60312 | Phospholipid-transporting ATPase VA | clinvar |
| ZEB2 | HGNC:14881 | ENSG00000169554 | O60315 | Zinc finger E-box-binding homeobox 2 | gwas |
| FANCL | HGNC:20748 | ENSG00000115392 | Q9NW38 | E3 ubiquitin-protein ligase FANCL | gwas |
| GABRA6 | HGNC:4080 | ENSG00000145863 | Q16445 | Gamma-aminobutyric acid receptor subunit alpha-6 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|
| SLC2A1 | Solute carrier family 2, facilitated glucose transporter member 1 | Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake. |
| CACNA1H | Voltage-dependent T-type calcium channel subunit alpha-1H | Voltage-sensitive calcium channel that gives rise to T-type calcium currents. |
| GABRB3 | Gamma-aminobutyric acid receptor subunit beta-3 | Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. |
| SCN1B | Sodium channel regulatory subunit beta-1 | Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes. |
| BCL11A | BCL11 transcription factor A | Transcription factor. |
| ATP10A | Phospholipid-transporting ATPase VA | Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane. |
| ZEB2 | Zinc finger E-box-binding homeobox 2 | Transcriptional inhibitor that binds to DNA sequence 5’-CACCT-3’ in different promoters. |
| FANCL | E3 ubiquitin-protein ligase FANCL | Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway. |
| GABRA6 | Gamma-aminobutyric acid receptor subunit alpha-6 | Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. |
Protein-family classification
Druggable: 3 · Difficult: 4 · Unknown: 2 · Druggable fraction: 0.33
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|
| Transcription factor | 4 | 3.7× | 0.082 |
| Ion channel | 1 | 12.4× | 0.183 |
| Transporter | 1 | 8.6× | 0.183 |
| Antibody/Immunoglobulin | 1 | 3.2× | 0.337 |
| Other/Unknown | 2 | 0.4× | 0.992 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|
| SLC2A1 | Transporter | yes | | Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like |
| CACNA1H | Ion channel | yes | | VDCC_T_a1, Ion_trans_dom, Volt_channel_dom_sf |
| GABRB3 | Other/Unknown | no | | GABAAb_rcpt, GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM |
| SCN1B | Antibody/Immunoglobulin | yes | | Ig_V-set, Ig-like_fold, Na_channel_b1/b3 |
| BCL11A | Transcription factor | no | | Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF |
| ATP10A | Transcription factor | no | 7.6.2.1 | P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf |
| ZEB2 | Transcription factor | no | | HD, Di19_Zn-bd, Homeodomain-like_sf |
| FANCL | Transcription factor | no | 2.3.2.27 | Znf_RING/FYVE/PHD, UBQ-conjugating_enzyme/RWD, FancL_WD-rpt_cont_dom |
| GABRA6 | Other/Unknown | no | | GABAAa_rcpt, GABBAa6_rcpt, GABAA/Glycine_rcpt |
Expression context
Cohort genes with no expression data: 0.
9 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|
| cortical plate | 3 |
| sural nerve | 2 |
| primary visual cortex | 2 |
| skin of abdomen | 1 |
| tibial nerve | 1 |
| lower esophagus | 1 |
| lower esophagus muscularis layer | 1 |
| muscle layer of sigmoid colon | 1 |
| Brodmann (1909) area 23 | 1 |
| middle temporal gyrus | 1 |
| cerebellum | 1 |
| right hemisphere of cerebellum | 1 |
| ganglionic eminence | 1 |
| descending thoracic aorta | 1 |
| endothelial cell | 1 |
| thoracic aorta | 1 |
| monocyte | 1 |
| adenohypophysis | 1 |
| calcaneal tendon | 1 |
| pituitary gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|
| SLC2A1 | 250 | ubiquitous | marker | tibial nerve, sural nerve, skin of abdomen |
| CACNA1H | 166 | broad | marker | lower esophagus muscularis layer, muscle layer of sigmoid colon, lower esophagus |
| GABRB3 | 219 | broad | marker | middle temporal gyrus, cortical plate, Brodmann (1909) area 23 |
| SCN1B | 133 | ubiquitous | marker | primary visual cortex, right hemisphere of cerebellum, cerebellum |
| BCL11A | 247 | ubiquitous | marker | cortical plate, ganglionic eminence, primary visual cortex |
| ATP10A | 229 | broad | marker | endothelial cell, descending thoracic aorta, thoracic aorta |
| ZEB2 | 290 | ubiquitous | marker | cortical plate, sural nerve, monocyte |
| FANCL | 293 | ubiquitous | marker | pituitary gland, adenohypophysis, calcaneal tendon |
| GABRA6 | 105 | tissue_specific | marker | cerebellar vermis, cerebellar cortex, cerebellar hemisphere |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|
| SLC2A1 | 5,711 |
| ZEB2 | 3,193 |
| BCL11A | 2,389 |
| GABRB3 | 1,972 |
| GABRA6 | 1,799 |
| FANCL | 1,621 |
| CACNA1H | 1,564 |
| SCN1B | 1,328 |
| ATP10A | 1,016 |
Intra-cohort edges
| A | B | Sources |
|---|
| ATP10A | GABRB3 | string_interaction |
| CACNA1H | GABRB3 | string_interaction |
| GABRA6 | GABRB3 | biogrid_interaction, intact |
| GABRA6 | SCN1B | string_interaction |
Structural data
PDB: 7 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|
| GABRB3 | P28472 | 95 |
| SCN1B | Q07699 | 39 |
| BCL11A | Q9H165 | 17 |
| FANCL | Q9NW38 | 8 |
| SLC2A1 | P11166 | 5 |
| CACNA1H | O95180 | 5 |
| ZEB2 | O60315 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|
| GABRA6 | Q16445 | 82.69 |
| ATP10A | O60312 | 71.30 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 41. Enrichment computed across 9 evidence-associated genes (9 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| GABA receptor activation | 2 | 70.5× | 0.014 | GABRA6, GABRB3 |
| Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1) | 1 | 1268.9× | 0.016 | SLC2A1 |
| Lactose synthesis | 1 | 423.0× | 0.032 | SLC2A1 |
| Vitamin C (ascorbate) metabolism | 1 | 158.6× | 0.039 | SLC2A1 |
| Formation of the posterior neural plate | 1 | 126.9× | 0.039 | ZEB2 |
| Regulation of CDH11 gene transcription | 1 | 115.3× | 0.039 | ZEB2 |
| Formation of the anterior neural plate | 1 | 115.3× | 0.039 | ZEB2 |
| ALK mutants bind TKIs | 1 | 105.7× | 0.039 | BCL11A |
| Positive Regulation of CDH1 Gene Transcription | 1 | 105.7× | 0.039 | ZEB2 |
| Muscle contraction | 2 | 17.1× | 0.039 | SCN1B, CACNA1H |
| Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1 | 74.6× | 0.048 | CACNA1H |
| Formation of the embryonic stem cell BAF (esBAF) complex | 1 | 66.8× | 0.048 | BCL11A |
| Cellular hexose transport | 1 | 60.4× | 0.048 | SLC2A1 |
| Axon guidance | 2 | 10.0× | 0.048 | SCN1B, CACNA1H |
| Nervous system development | 2 | 9.5× | 0.048 | SCN1B, CACNA1H |
| Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 1 | 50.8× | 0.050 | BCL11A |
| Interaction between L1 and Ankyrins | 1 | 40.9× | 0.054 | SCN1B |
| Phase 0 - rapid depolarisation | 1 | 38.5× | 0.054 | SCN1B |
| Sensory perception of taste | 1 | 37.3× | 0.054 | SCN1B |
| Fanconi Anemia Pathway | 1 | 30.9× | 0.054 | FANCL |
| Sensory perception of sweet, bitter, and umami (glutamate) taste | 1 | 30.9× | 0.054 | SCN1B |
| Signaling by ERBB4 | 1 | 30.2× | 0.054 | GABRB3 |
| NCAM signaling for neurite out-growth | 1 | 30.2× | 0.054 | CACNA1H |
| Signaling by ALK in cancer | 1 | 30.2× | 0.054 | BCL11A |
| Smooth Muscle Contraction | 1 | 29.5× | 0.054 | CACNA1H |
| Cellular responses to mechanical stimuli | 1 | 28.8× | 0.054 | CACNA1H |
| NCAM1 interactions | 1 | 27.6× | 0.054 | CACNA1H |
| Regulation of insulin secretion | 1 | 24.4× | 0.059 | SLC2A1 |
| Ion transport by P-type ATPases | 1 | 23.1× | 0.060 | ATP10A |
| Signaling by ALK fusions and activated point mutants | 1 | 16.7× | 0.080 | BCL11A |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| inhibitory synapse assembly | 2 | 138.7× | 0.006 | GABRA6, GABRB3 |
| gamma-aminobutyric acid signaling pathway | 2 | 120.8× | 0.006 | GABRA6, GABRB3 |
| synaptic transmission, GABAergic | 2 | 110.1× | 0.006 | GABRA6, GABRB3 |
| reproductive behavior | 1 | 1872.4× | 0.006 | GABRB3 |
| corticospinal neuron axon guidance | 1 | 1872.4× | 0.006 | SCN1B |
| circadian sleep/wake cycle, REM sleep | 1 | 1872.4× | 0.006 | GABRB3 |
| mammillary axonal complex development | 1 | 1872.4× | 0.006 | ZEB2 |
| positive regulation of myofibroblast contraction | 1 | 1872.4× | 0.006 | ZEB2 |
| negative regulation of neuron remodeling | 1 | 1872.4× | 0.006 | BCL11A |
| regulation of blood-brain barrier permeability | 1 | 1872.4× | 0.006 | ZEB2 |
| negative regulation of branching morphogenesis of a nerve | 1 | 1872.4× | 0.006 | BCL11A |
| chloride transmembrane transport | 2 | 52.7× | 0.007 | GABRA6, GABRB3 |
| positive regulation of lens fiber cell differentiation | 1 | 936.2× | 0.009 | ZEB2 |
| regulation of melanosome organization | 1 | 936.2× | 0.009 | ZEB2 |
| regulation of myofibroblast cell apoptotic process | 1 | 936.2× | 0.009 | ZEB2 |
| negative regulation of protein homooligomerization | 1 | 624.1× | 0.010 | BCL11A |
| membrane depolarization during Purkinje myocyte cell action potential | 1 | 624.1× | 0.010 | SCN1B |
| melanocyte migration | 1 | 624.1× | 0.010 | ZEB2 |
| positive regulation of membrane tubulation | 1 | 624.1× | 0.010 | ATP10A |
| response to Thyroglobulin triiodothyronine | 1 | 624.1× | 0.010 | SLC2A1 |
| positive regulation of voltage-gated sodium channel activity | 1 | 624.1× | 0.010 | SCN1B |
| positive regulation of neuron projection development | 2 | 30.4× | 0.011 | SCN1B, BCL11A |
| long-chain fatty acid import across plasma membrane | 1 | 468.1× | 0.011 | SLC2A1 |
| GDP-L-fucose salvage | 1 | 468.1× | 0.011 | SLC2A1 |
| negative regulation of dendrite extension | 1 | 468.1× | 0.011 | BCL11A |
| aldosterone biosynthetic process | 1 | 374.5× | 0.012 | CACNA1H |
| myofibroblast differentiation | 1 | 374.5× | 0.012 | ZEB2 |
| positive regulation of melanocyte differentiation | 1 | 374.5× | 0.012 | ZEB2 |
| central nervous system development | 2 | 25.6× | 0.012 | SLC2A1, ZEB2 |
| cellular response to histamine | 1 | 312.1× | 0.013 | GABRB3 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 4
Druggability breadth: 6 of 9 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|
| GABRB3 | 32 | 4 |
| GABRA6 | 19 | 4 |
| CACNA1H | 10 | 4 |
| SLC2A1 | 7 | 4 |
| SCN1B | 2 | 2 |
| BCL11A | 0 | 0 |
| ATP10A | 0 | 0 |
| ZEB2 | 0 | 0 |
| FANCL | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|
| EMETINE | 4 | SLC2A1 |
| PIMOZIDE | 4 | CACNA1H |
| MIBEFRADIL | 4 | CACNA1H |
| NIMODIPINE | 4 | CACNA1H |
| TACRINE | 4 | CACNA1H |
| LINDANE | 4 | GABRA6, GABRB3 |
| PENTOBARBITAL | 4 | GABRB3 |
| ENZALUTAMIDE | 4 | GABRA6, GABRB3 |
| DIAZEPAM | 4 | GABRA6, GABRB3 |
| LIOTHYRONINE | 4 | GABRA6, GABRB3 |
| GANAXOLONE | 4 | GABRA6, GABRB3 |
| BREXANOLONE | 4 | GABRA6, GABRB3 |
| APALUTAMIDE | 4 | GABRA6, GABRB3 |
| FLUMAZENIL | 4 | GABRA6, GABRB3 |
| CLONAZEPAM | 4 | GABRA6, GABRB3 |
| FLUNITRAZEPAM | 4 | GABRB3 |
| CHLORDIAZEPOXIDE | 4 | GABRB3 |
| TRIAZOLAM | 4 | GABRB3 |
| ZOLPIDEM | 4 | GABRB3 |
| PROPOFOL | 4 | GABRA6, GABRB3 |
| ZALEPLON | 4 | GABRB3 |
| ZURANOLONE | 4 | GABRB3 |
| GOSSYPOL | 3 | SLC2A1 |
| CILNIDIPINE | 3 | CACNA1H |
| CYCLOHEXIMIDE | 2 | SLC2A1 |
| GENISTEIN | 2 | SLC2A1 |
| COLFORSIN | 2 | SLC2A1 |
| SUVECALTAMIDE | 2 | CACNA1H |
| FLUNARIZINE | 2 | CACNA1H |
| APINOCALTAMIDE | 2 | CACNA1H |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|
| GABRB3 | 887 | Binding:722, Functional:156, ADMET:6, Toxicity:3 |
| GABRA6 | 264 | Binding:227, Functional:33, Toxicity:3, ADMET:1 |
| SLC2A1 | 158 | Binding:130, ADMET:24, Functional:4 |
| CACNA1H | 124 | Binding:102, Functional:17, ADMET:4, Toxicity:1 |
| SCN1B | 15 | Binding:7, ADMET:6, Toxicity:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|
| ATP10A | 7.6.2.1 | P-type phospholipid transporter |
| FANCL | 2.3.2.27 | RING-type E3 ubiquitin transferase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|
| SLC2A1 | 158 |
| CACNA1H | 124 |
| GABRB3 | 887 |
| GABRA6 | 264 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|
| EMETINE | 4 | SLC2A1 |
| PIMOZIDE | 4 | CACNA1H |
| MIBEFRADIL | 4 | CACNA1H |
| NIMODIPINE | 4 | CACNA1H |
| TACRINE | 4 | CACNA1H |
| LINDANE | 4 | GABRA6, GABRB3 |
| PENTOBARBITAL | 4 | GABRB3 |
| ENZALUTAMIDE | 4 | GABRA6, GABRB3 |
| DIAZEPAM | 4 | GABRA6, GABRB3 |
| LIOTHYRONINE | 4 | GABRA6, GABRB3 |
| GANAXOLONE | 4 | GABRA6, GABRB3 |
| BREXANOLONE | 4 | GABRA6, GABRB3 |
| APALUTAMIDE | 4 | GABRA6, GABRB3 |
| FLUMAZENIL | 4 | GABRA6, GABRB3 |
| CLONAZEPAM | 4 | GABRA6, GABRB3 |
| FLUNITRAZEPAM | 4 | GABRB3 |
| CHLORDIAZEPOXIDE | 4 | GABRB3 |
| TRIAZOLAM | 4 | GABRB3 |
| ZOLPIDEM | 4 | GABRB3 |
| PROPOFOL | 4 | GABRA6, GABRB3 |
| ZALEPLON | 4 | GABRB3 |
| ZURANOLONE | 4 | GABRB3 |
| GOSSYPOL | 3 | SLC2A1 |
| CILNIDIPINE | 3 | CACNA1H |
| CYCLOHEXIMIDE | 2 | SLC2A1 |
| GENISTEIN | 2 | SLC2A1 |
| COLFORSIN | 2 | SLC2A1 |
| SUVECALTAMIDE | 2 | CACNA1H |
| FLUNARIZINE | 2 | CACNA1H |
| APINOCALTAMIDE | 2 | CACNA1H |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|
| A | Approved (phase 4 drug) | 4 | SLC2A1, CACNA1H, GABRB3, GABRA6 |
| B | Phased (≥1) drug, not yet approved | 1 | SCN1B |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 4 | BCL11A, ATP10A, ZEB2, FANCL |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|
| BCL11A | 0 | — |
| ATP10A | 0 | — |
| ZEB2 | 0 | — |
| FANCL | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 11.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|
| PHASE3 | 4 |
| Not specified | 4 |
| PHASE2 | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|
| NCT04666610 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study to Evaluate the Efficacy, Safety, and Tolerability of Brivaracetam as Monotherapy in Patients 2 to 25 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy |
| NCT06315322 | PHASE3 | RECRUITING | A Study to Test the Long-term Safety and Tolerability of Brivaracetam in Study Participants With Childhood Absence Epilepsy or Juvenile Absence Epilepsy |
| NCT00088452 | PHASE3 | COMPLETED | Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study |
| NCT05109234 | PHASE3 | COMPLETED | A Study to Test the Long-term Safety, Tolerability and Efficacy of Brivaracetam in Study Participants 2 to 26 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy |
| NCT03336242 | PHASE2 | TERMINATED | Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures |
| NCT03355300 | PHASE2 | TERMINATED | Long-Term Safety of Pharmaceutical Grade Synthetic Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures |
| NCT06153186 | PHASE2 | TERMINATED | Flunarizine for Treatment Resistant Absence Epilepsy |
| NCT00041951 | Not specified | COMPLETED | Search for Genes Influencing Childhood Absence Epilepsy (CAE) Study |
| NCT00361010 | Not specified | COMPLETED | A Pilot Study of Efficacy and Tolerability of Levetiracetam Monotherapy in Subjects With Childhood Absence Epilepsy |
| NCT00393666 | Not specified | COMPLETED | Why Are Patients With Absence Seizures Absent? A Brain Imaging Study |
| NCT06310772 | Not specified | COMPLETED | Assessing Comorbidities in Epilepsy Using Eye Movement Recordings |
Drugs tested across these trials (top 30)
- Cohort genes: SLC2A1, CACNA1H, GABRB3, SCN1B, BCL11A, ATP10A, ZEB2, FANCL, GABRA6
- Drugs: Brivaracetam, Cannabidiol, Ethosuximide, Lamotrigine, Valproic Acid