Developmental and epileptic encephalopathy, 43

Summary

Developmental and epileptic encephalopathy, 43 (MONDO:0014921) is a disease caused by GABRB3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: GABRB3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 72

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 43
Mondo ID	MONDO:0014921
OMIM	617113
DOID	DOID:0080447
UMLS	C4310712
MedGen	934679
GARD	0016192
Is cancer (heuristic)	no

Also known as: DEE43 · developmental and epileptic encephalopathy 43 · early infantile epileptic encephalopathy caused by mutation in GABRB3 · EIEE43 · epileptic encephalopathy, early infantile, 43 · epileptic encephalopathy, early infantile, 43; EIEE43 · epileptic encephalopathy, early infantile, type 43 · GABRB3 early infantile epileptic encephalopathy

Data availability: 72 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Lennox-Gastaut syndrome › developmental and epileptic encephalopathy, 43

Related subtypes (2): developmental and epileptic encephalopathy 94, developmental and epileptic encephalopathy, 31A

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

72 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 16 likely pathogenic, 11 pathogenic, 10 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 3 benign/likely benign, 1 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1003531	NM_000814.6(GABRB3):c.911A>G (p.Lys304Arg)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164045	NM_000814.6(GABRB3):c.675C>G (p.Phe225Leu)	GABRB3	Pathogenic	no assertion criteria provided
1324443	NM_000814.6(GABRB3):c.914C>T (p.Ala305Val)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453717	NM_000814.6(GABRB3):c.860C>T (p.Thr287Ile)	GABRB3	Pathogenic	criteria provided, single submitter
1723205	NM_000814.6(GABRB3):c.580C>T (p.Arg194Ter)	GABRB3	Pathogenic	criteria provided, multiple submitters, no conflicts
2098861	NM_000814.6(GABRB3):c.154C>G (p.Leu52Val)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2500725	NM_000814.6(GABRB3):c.929T>G (p.Leu310Arg)	GABRB3	Pathogenic	criteria provided, single submitter
254261	NM_000814.6(GABRB3):c.358G>A (p.Asp120Asn)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254262	NM_000814.6(GABRB3):c.545A>T (p.Tyr182Phe)	GABRB3	Pathogenic	no assertion criteria provided
254263	NM_000814.6(GABRB3):c.745C>A (p.Gln249Lys)	GABRB3	Pathogenic	no assertion criteria provided
254264	NM_000814.6(GABRB3):c.913G>A (p.Ala305Thr)	GABRB3	Pathogenic	no assertion criteria provided
3251936	NM_000814.6(GABRB3):c.76C>T (p.Gln26Ter)	GABRB3	Pathogenic	criteria provided, single submitter
3600364	NM_000814.6(GABRB3):c.238A>G (p.Met80Val)	GABRB3	Pathogenic	criteria provided, single submitter
3894574	NM_000814.6(GABRB3):c.360C>G (p.Asp120Glu)	GABRB3	Pathogenic	criteria provided, single submitter
423595	NM_000814.6(GABRB3):c.758C>T (p.Pro253Leu)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
653036	NM_000814.6(GABRB3):c.331C>T (p.Arg111Ter)	GABRB3	Pathogenic	criteria provided, multiple submitters, no conflicts
839250	NM_000814.6(GABRB3):c.905A>G (p.Tyr302Cys)	GABRB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028379	NM_000814.6(GABRB3):c.496A>G (p.Arg166Gly)	GABRB3	Likely pathogenic	criteria provided, single submitter
1320161	NM_000814.6(GABRB3):c.778C>G (p.Leu260Val)	GABRB3	Likely pathogenic	criteria provided, single submitter
2442349	NM_000814.6(GABRB3):c.493C>T (p.Leu165Phe)	GABRB3	Likely pathogenic	criteria provided, single submitter
3359062	NM_000814.6(GABRB3):c.845C>G (p.Thr282Ser)	GABRB3	Likely pathogenic	criteria provided, single submitter
3376132	NM_000814.6(GABRB3):c.730G>A (p.Gly244Arg)	GABRB3	Likely pathogenic	criteria provided, single submitter
3602133	NM_000814.6(GABRB3):c.154C>A (p.Leu52Ile)	GABRB3	Likely pathogenic	criteria provided, single submitter
3754031	NM_000814.6(GABRB3):c.229G>C (p.Glu77Gln)	GABRB3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3770196	NM_000814.6(GABRB3):c.553A>G (p.Thr185Ala)	GABRB3	Likely pathogenic	criteria provided, single submitter
4292724	NM_000814.6(GABRB3):c.919G>T (p.Asp307Tyr)	GABRB3	Likely pathogenic	criteria provided, single submitter
4292880	NM_000814.6(GABRB3):c.976T>A (p.Phe326Ile)	GABRB3	Likely pathogenic	criteria provided, single submitter
4819143	NM_000814.6(GABRB3):c.982A>T (p.Asn328Tyr)	GABRB3	Likely pathogenic	criteria provided, single submitter
837360	NM_000814.6(GABRB3):c.902C>T (p.Pro301Leu)	GABRB3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
870184	NM_000814.6(GABRB3):c.733T>C (p.Tyr245His)	GABRB3	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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	developmental and epileptic encephalopathy, 43	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GABRB3	Orphanet:2382	Lennox-Gastaut syndrome
GABRB3	Orphanet:64280	Childhood absence epilepsy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GABRB3	HGNC:4083	ENSG00000166206	P28472	Gamma-aminobutyric acid receptor subunit beta-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GABRB3	Other/Unknown	no		GABAAb_rcpt, GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
cortical plate	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GABRB3	219	broad	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GABRB3	1,972

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GABRB3	P28472	95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	317.2×	0.004	GABRB3
Signaling by ERBB4	1	271.9×	0.004	GABRB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reproductive behavior	1	16852.0×	7e-04	GABRB3
circadian sleep/wake cycle, REM sleep	1	16852.0×	7e-04	GABRB3
cellular response to histamine	1	2808.7×	0.002	GABRB3
response to anesthetic	1	2808.7×	0.002	GABRB3
inner ear receptor cell development	1	2407.4×	0.002	GABRB3
hard palate development	1	1685.2×	0.002	GABRB3
inhibitory postsynaptic potential	1	1685.2×	0.002	GABRB3
innervation	1	887.0×	0.003	GABRB3
cellular response to zinc ion	1	674.1×	0.003	GABRB3
exploration behavior	1	648.1×	0.003	GABRB3
inhibitory synapse assembly	1	624.1×	0.003	GABRB3
motor behavior	1	561.7×	0.003	GABRB3
gamma-aminobutyric acid signaling pathway	1	543.6×	0.003	GABRB3
synaptic transmission, GABAergic	1	495.6×	0.003	GABRB3
cochlea development	1	468.1×	0.003	GABRB3
cerebellum development	1	358.6×	0.004	GABRB3
learning	1	280.9×	0.005	GABRB3
social behavior	1	271.8×	0.005	GABRB3
roof of mouth development	1	247.8×	0.005	GABRB3
chloride transmembrane transport	1	237.3×	0.005	GABRB3
memory	1	183.2×	0.006	GABRB3
response to xenobiotic stimulus	1	69.1×	0.015	GABRB3
signal transduction	1	16.1×	0.062	GABRB3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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.

Symbol	Example approved molecule
GABRB3	LINDANE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GABRB3	32	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LINDANE	4	GABRB3
PENTOBARBITAL	4	GABRB3
ENZALUTAMIDE	4	GABRB3
DIAZEPAM	4	GABRB3
LIOTHYRONINE	4	GABRB3
GANAXOLONE	4	GABRB3
BREXANOLONE	4	GABRB3
APALUTAMIDE	4	GABRB3
FLUMAZENIL	4	GABRB3
CLONAZEPAM	4	GABRB3
FLUNITRAZEPAM	4	GABRB3
CHLORDIAZEPOXIDE	4	GABRB3
TRIAZOLAM	4	GABRB3
ZOLPIDEM	4	GABRB3
PROPOFOL	4	GABRB3
ZALEPLON	4	GABRB3
ZURANOLONE	4	GABRB3
DELORAZEPAM	2	GABRB3
FLAVONE	2	GABRB3
PROGABIDE	2	GABRB3
ABECARNIL	2	GABRB3
BAICALEIN	2	GABRB3
MK-0777	2	GABRB3
DARIGABAT	2	GABRB3
BRETAZENIL	2	GABRB3
LORECLEZOLE	2	GABRB3
ALFAXALONE	2	GABRB3
BASMISANIL	2	GABRB3
AZD7325	2	GABRB3
MUSCIMOL	1	GABRB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GABRB3	887	Binding:722, Functional:156, ADMET:6, Toxicity:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GABRB3	887

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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)
LINDANE	4	GABRB3
PENTOBARBITAL	4	GABRB3
ENZALUTAMIDE	4	GABRB3
DIAZEPAM	4	GABRB3
LIOTHYRONINE	4	GABRB3
GANAXOLONE	4	GABRB3
BREXANOLONE	4	GABRB3
APALUTAMIDE	4	GABRB3
FLUMAZENIL	4	GABRB3
CLONAZEPAM	4	GABRB3
FLUNITRAZEPAM	4	GABRB3
CHLORDIAZEPOXIDE	4	GABRB3
TRIAZOLAM	4	GABRB3
ZOLPIDEM	4	GABRB3
PROPOFOL	4	GABRB3
ZALEPLON	4	GABRB3
ZURANOLONE	4	GABRB3
DELORAZEPAM	2	GABRB3
FLAVONE	2	GABRB3
PROGABIDE	2	GABRB3
ABECARNIL	2	GABRB3
BAICALEIN	2	GABRB3
MK-0777	2	GABRB3
DARIGABAT	2	GABRB3
BRETAZENIL	2	GABRB3
LORECLEZOLE	2	GABRB3
ALFAXALONE	2	GABRB3
BASMISANIL	2	GABRB3
AZD7325	2	GABRB3
MUSCIMOL	1	GABRB3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GABRB3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.