Developmental and epileptic encephalopathy 92

disease

On this page

Also known as DEE92epileptic encephalopathy, infantile or early childhood, 2IECEE2

Summary

Developmental and epileptic encephalopathy 92 (MONDO:0020631) is a disease caused by GABRB2 (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: GABRB2 (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 60

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 92
Mondo ID	MONDO:0020631
OMIM	617829
DOID	DOID:0080471
UMLS	C4693362
MedGen	1638319
GARD	0016258
Is cancer (heuristic)	no

Also known as: DEE92 · developmental and epileptic encephalopathy 92 · epileptic encephalopathy, infantile or early childhood, 2 · IECEE2

Data availability: 60 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy 92

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

60 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 11 likely pathogenic, 7 pathogenic, 6 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076207	NM_001371727.1(GABRB2):c.902A>T (p.Tyr301Phe)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161444	NM_001371727.1(GABRB2):c.236T>C (p.Met79Thr)	GABRB2	Pathogenic	no assertion criteria provided
265166	NM_001371727.1(GABRB2):c.909G>T (p.Lys303Asn)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3893240	NM_001371727.1(GABRB2):c.542A>T (p.Tyr181Phe)	GABRB2	Pathogenic	criteria provided, single submitter
421234	NM_001371727.1(GABRB2):c.902A>G (p.Tyr301Cys)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427157	NM_001371727.1(GABRB2):c.904G>A (p.Val302Met)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
464940	NM_001371727.1(GABRB2):c.877C>T (p.Arg293Trp)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
487680	NM_001371727.1(GABRB2):c.859A>C (p.Thr287Pro)	GABRB2	Pathogenic	no assertion criteria provided
487681	NM_001371727.1(GABRB2):c.908A>G (p.Lys303Arg)	GABRB2	Pathogenic	no assertion criteria provided
487682	NM_001371727.1(GABRB2):c.730T>C (p.Tyr244His)	GABRB2	Pathogenic	no assertion criteria provided
487683	NM_001371727.1(GABRB2):c.830T>C (p.Leu277Ser)	GABRB2	Pathogenic	criteria provided, single submitter
546260	NM_001371727.1(GABRB2):c.946G>A (p.Val316Ile)	GABRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
972959	NM_001371727.1(GABRB2):c.910G>A (p.Ala304Thr)	GABRB2	Pathogenic	criteria provided, single submitter
1333488	NM_001371727.1(GABRB2):c.627G>T (p.Gln209His)	GABRB2	Likely pathogenic	criteria provided, single submitter
1338859	NM_001371727.1(GABRB2):c.754C>T (p.Pro252Ser)	GABRB2	Likely pathogenic	criteria provided, single submitter
1342899	NM_001371727.1(GABRB2):c.857C>T (p.Thr286Ile)	GABRB2	Likely pathogenic	criteria provided, single submitter
1803031	NM_001371727.1(GABRB2):c.929T>C (p.Met310Thr)	GABRB2	Likely pathogenic	criteria provided, single submitter
224810	NM_001371727.1(GABRB2):c.754C>G (p.Pro252Ala)	GABRB2	Likely pathogenic	criteria provided, single submitter
3061923	NM_001371727.1(GABRB2):c.242A>G (p.Tyr81Cys)	GABRB2	Likely pathogenic	criteria provided, single submitter
4531980	NM_001371727.1(GABRB2):c.486G>A (p.Met162Ile)	GABRB2	Likely pathogenic	criteria provided, single submitter
4819807	NM_001371727.1(GABRB2):c.863T>A (p.Ile288Asn)	GABRB2	Likely pathogenic	criteria provided, single submitter
973184	NM_001371727.1(GABRB2):c.754C>A (p.Pro252Thr)	GABRB2	Likely pathogenic	criteria provided, single submitter
983416	NM_001371727.1(GABRB2):c.895A>G (p.Ile299Val)	GABRB2	Likely pathogenic	criteria provided, single submitter
984724	NM_001371727.1(GABRB2):c.986T>A (p.Ile329Asn)	GABRB2	Likely pathogenic	no assertion criteria provided
265164	NM_001371727.1(GABRB2):c.578G>A (p.Arg193His)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533531	NM_001371727.1(GABRB2):c.1190C>T (p.Thr397Met)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
656109	NM_001371727.1(GABRB2):c.1325G>A (p.Arg442Gln)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
835272	NM_001371727.1(GABRB2):c.914T>C (p.Ile305Thr)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930595	NM_001371727.1(GABRB2):c.475G>T (p.Ala159Ser)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
949052	NM_001371727.1(GABRB2):c.860C>T (p.Thr287Ile)	GABRB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
GABRB2	Definitive	Autosomal dominant	developmental and epileptic encephalopathy 92	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GABRB2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
KMT2C	Orphanet:261652	Kleefstra syndrome due to a point mutation

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GABRB2	HGNC:4082	ENSG00000145864	P47870	Gamma-aminobutyric acid receptor subunit beta-2	gencc,clinvar
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GABRB2	Gamma-aminobutyric acid receptor subunit beta-2	Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GABRB2	Other/Unknown	no		GABAAb_rcpt, GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
endothelial cell	1
lateral nuclear group of thalamus	1
caput epididymis	1
oocyte	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GABRB2	198	broad	marker	Brodmann (1909) area 23, endothelial cell, lateral nuclear group of thalamus
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KMT2C	3,321
GABRB2	2,186

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GABRB2	P47870	31
KMT2C	Q8NEZ4	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of HOX genes during differentiation	1	219.6×	0.030	KMT2C
GABA receptor activation	1	158.6×	0.030	GABRB2
Signaling by ERBB4	1	135.9×	0.030	GABRB2
Formation of WDR5-containing histone-modifying complexes	1	132.8×	0.030	KMT2C
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	107.7×	0.030	KMT2C
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	98.5×	0.030	KMT2C
PKMTs methylate histone lysines	1	80.4×	0.030	KMT2C
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.030	KMT2C
Transcriptional regulation by RUNX1	1	73.2×	0.030	KMT2C
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	60.1×	0.033	KMT2C
Regulation of PD-L1(CD274) transcription	1	54.4×	0.033	KMT2C
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.035	KMT2C
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.035	KMT2C
Chromatin organization	1	40.8×	0.035	KMT2C
Chromatin modifying enzymes	1	36.1×	0.035	KMT2C
Epigenetic regulation of gene expression	1	35.7×	0.035	KMT2C
RNA Polymerase II Transcription	1	11.3×	0.102	KMT2C
Gene expression (Transcription)	1	8.9×	0.121	KMT2C
Generic Transcription Pathway	1	7.5×	0.134	KMT2C
Developmental Biology	1	7.2×	0.134	KMT2C

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to histamine	1	1404.3×	0.005	GABRB2
inner ear receptor cell development	1	1203.7×	0.005	GABRB2
innervation	1	443.5×	0.007	GABRB2
inhibitory synapse assembly	1	312.1×	0.007	GABRB2
gamma-aminobutyric acid signaling pathway	1	271.8×	0.007	GABRB2
synaptic transmission, GABAergic	1	247.8×	0.007	GABRB2
cochlea development	1	234.1×	0.007	GABRB2
chloride transmembrane transport	1	118.7×	0.012	GABRB2
methylation	1	85.1×	0.014	KMT2C
chemical synaptic transmission	1	38.6×	0.028	GABRB2
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	KMT2C

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
GABRB2	CANNABIDIOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GABRB2	47	4
KMT2C	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABIDIOL	4	GABRB2
ENZALUTAMIDE	4	GABRB2
DIAZEPAM	4	GABRB2
LIOTHYRONINE	4	GABRB2
GANAXOLONE	4	GABRB2
BREXANOLONE	4	GABRB2
APALUTAMIDE	4	GABRB2
FLUMAZENIL	4	GABRB2
CLONAZEPAM	4	GABRB2
FLUNITRAZEPAM	4	GABRB2
ZALEPLON	4	GABRB2
STIRIPENTOL	4	GABRB2
ZURANOLONE	4	GABRB2
PROPOFOL	4	GABRB2
ALPRAZOLAM	4	GABRB2
ETOMIDATE	4	GABRB2
ZOLPIDEM	4	GABRB2
ESZOPICLONE	4	GABRB2
PENTOBARBITAL	4	GABRB2
CANDESARTAN CILEXETIL	4	GABRB2
SIMVASTATIN	4	GABRB2
EPINASTINE	4	GABRB2
GLAFENINE	4	GABRB2
TIPRANAVIR	4	GABRB2
BENPERIDOL	4	GABRB2
ASENAPINE	4	GABRB2
TROGLITAZONE	4	GABRB2
CLOZAPINE	4	GABRB2
CHLORAMBUCIL	4	GABRB2
CRIZOTINIB	4	GABRB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GABRB2	549	Binding:463, Functional:81, Toxicity:4, ADMET:1
KMT2C	29	Binding:29

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GABRB2	549

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
CANNABIDIOL	4	GABRB2
ENZALUTAMIDE	4	GABRB2
DIAZEPAM	4	GABRB2
LIOTHYRONINE	4	GABRB2
GANAXOLONE	4	GABRB2
BREXANOLONE	4	GABRB2
APALUTAMIDE	4	GABRB2
FLUMAZENIL	4	GABRB2
CLONAZEPAM	4	GABRB2
FLUNITRAZEPAM	4	GABRB2
ZALEPLON	4	GABRB2
STIRIPENTOL	4	GABRB2
ZURANOLONE	4	GABRB2
PROPOFOL	4	GABRB2
ALPRAZOLAM	4	GABRB2
ETOMIDATE	4	GABRB2
ZOLPIDEM	4	GABRB2
ESZOPICLONE	4	GABRB2
PENTOBARBITAL	4	GABRB2
CANDESARTAN CILEXETIL	4	GABRB2
SIMVASTATIN	4	GABRB2
EPINASTINE	4	GABRB2
GLAFENINE	4	GABRB2
TIPRANAVIR	4	GABRB2
BENPERIDOL	4	GABRB2
ASENAPINE	4	GABRB2
TROGLITAZONE	4	GABRB2
CLOZAPINE	4	GABRB2
CHLORAMBUCIL	4	GABRB2
CRIZOTINIB	4	GABRB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GABRB2
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	1	KMT2C

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KMT2C	29	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: GABRB2, KMT2C