Developmental and epileptic encephalopathy, 79

Summary

Developmental and epileptic encephalopathy, 79 (MONDO:0032813) is a disease caused by GABRA5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GABRA5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 79
Mondo ID	MONDO:0032813
OMIM	618559
DOID	DOID:0112215
UMLS	C5231410
MedGen	1684738
GARD	0016366
Is cancer (heuristic)	no

Also known as: DEE79 · developmental and epileptic encephalopathy 79 · EIEE79 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 79 · epileptic encephalopathy, early infantile, 79

Data availability: 26 ClinVar variants · 3 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, 79

Related subtypes (104): developmental and epileptic encephalopathy, 9, developmental and epileptic encephalopathy, 8, developmental and epileptic encephalopathy, 2, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 3, developmental and epileptic encephalopathy, 4, microcephaly, seizures, and developmental delay, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 7, developmental and epileptic encephalopathy, 11, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 14, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 17, developmental and epileptic encephalopathy, 18, developmental and epileptic encephalopathy, 19, developmental and epileptic encephalopathy, 23, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 50, developmental and epileptic encephalopathy, 35, developmental and epileptic encephalopathy, 37, developmental and epileptic encephalopathy, 38, developmental and epileptic encephalopathy, 40, developmental and epileptic encephalopathy, 48, developmental and epileptic encephalopathy, 49, developmental and epileptic encephalopathy, 51, Lennox-Gastaut syndrome, developmental and epileptic encephalopathy 91, developmental and epileptic encephalopathy 92, developmental and epileptic encephalopathy 93, developmental and epileptic encephalopathy 96, developmental and epileptic encephalopathy, 90, developmental and epileptic encephalopathy, 85, with or without midline brain defects, developmental and epileptic encephalopathy, 67, developmental and epileptic encephalopathy, 86, developmental and epileptic encephalopathy, 87, developmental and epileptic encephalopathy, 88, developmental and epileptic encephalopathy 6B, developmental and epileptic encephalopathy 97, developmental and epileptic encephalopathy 98, developmental and epileptic encephalopathy 99, developmental and epileptic encephalopathy 100, developmental and epileptic encephalopathy 101, developmental and epileptic encephalopathy 89, developmental and epileptic encephalopathy 102, developmental and epileptic encephalopathy 103, developmental and epileptic encephalopathy 104, developmental and epileptic encephalopathy 105 with hypopituitarism, developmental and epileptic encephalopathy 106, developmental and epileptic encephalopathy 107, developmental and epileptic encephalopathy, 68, developmental and epileptic encephalopathy, 69, developmental and epileptic encephalopathy, 70, developmental and epileptic encephalopathy, 71, developmental and epileptic encephalopathy, 72, developmental and epileptic encephalopathy, 74, developmental and epileptic encephalopathy, 75, developmental and epileptic encephalopathy, 76, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 78, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 81, developmental and epileptic encephalopathy, 82, developmental and epileptic encephalopathy, 83, developmental and epileptic encephalopathy, 84, developmental and epileptic encephalopathy, 52, developmental and epileptic encephalopathy, 53, developmental and epileptic encephalopathy, 54, developmental and epileptic encephalopathy, 55, developmental and epileptic encephalopathy, 56, developmental and epileptic encephalopathy, 57, developmental and epileptic encephalopathy, 58, developmental and epileptic encephalopathy, 59, developmental and epileptic encephalopathy, 60, developmental and epileptic encephalopathy, 61, developmental and epileptic encephalopathy, 62, developmental and epileptic encephalopathy, 63, developmental and epileptic encephalopathy, 64, developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 73, developmental and epileptic encephalopathy, 66, developmental and epileptic encephalopathy, 6A, non-neonatal early infantile epileptic encephalopathy, Dravet syndrome, neonatal-onset developmental and epileptic encephalopathy, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, DNM1-encephalopathy and neurodevelopmental disorder, TMEM63B-related developmental and epileptic encephalopathy with anemia, developmental and epileptic encephalopathy 108, developmental and epileptic encephalopathy 109, developmental and epileptic encephalopathy 110, developmental and epileptic encephalopathy 111, developmental and epileptic encephalopathy 112, developmental and epileptic encephalopathy 113, developmental and epileptic encephalopathy 114, developmental and epileptic encephalopathy 115, developmental and epileptic encephalopathy 116, developmental and epileptic encephalopathy 118, developmental and epileptic encephalopathy 120, developmental and epileptic encephalopathy 121, developmental and epileptic encephalopathy 119

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

26 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 4 benign, 3 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
689391	NM_000810.4(GABRA5):c.880G>C (p.Val294Leu)	GABRA5	Pathogenic	no assertion criteria provided
689392	NM_000810.4(GABRA5):c.880G>T (p.Val294Phe)	GABRA5	Pathogenic	criteria provided, single submitter
689393	NM_000810.4(GABRA5):c.1238C>T (p.Ser413Phe)	GABRA5	Pathogenic	no assertion criteria provided
801399	NM_000810.4(GABRA5):c.902C>G (p.Thr301Arg)	GABRA5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1693318	NM_000810.4(GABRA5):c.902C>T (p.Thr301Met)	GABRA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1385912	NM_000810.4(GABRA5):c.998C>T (p.Ser333Leu)	GABRA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2432001	NM_000810.4(GABRA5):c.74C>G (p.Ser25Cys)	GABRA5	Uncertain significance	criteria provided, single submitter
2432002	NM_000810.4(GABRA5):c.983_988del (p.Tyr328_Ala329del)	GABRA5	Uncertain significance	criteria provided, single submitter
2432003	NM_000810.4(GABRA5):c.990C>T (p.Phe330=)	GABRA5	Uncertain significance	criteria provided, single submitter
2585483	NM_000810.4(GABRA5):c.313A>G (p.Lys105Glu)	GABRA5	Uncertain significance	criteria provided, single submitter
3067828	NM_000810.4(GABRA5):c.551C>T (p.Ala184Val)	GABRA5	Uncertain significance	criteria provided, single submitter
3377666	NM_000810.4(GABRA5):c.1372G>C (p.Ala458Pro)	GABRA5	Uncertain significance	criteria provided, single submitter
3382578	NM_000810.4(GABRA5):c.1327G>C (p.Val443Leu)	GABRA5	Uncertain significance	criteria provided, single submitter
3393270	NM_000810.4(GABRA5):c.259G>C (p.Val87Leu)	GABRA5	Uncertain significance	criteria provided, single submitter
4056502	NM_000810.4(GABRA5):c.1322A>C (p.Asn441Thr)	GABRA5	Uncertain significance	criteria provided, single submitter
4056503	NM_000810.4(GABRA5):c.581A>T (p.Tyr194Phe)	GABRA5	Uncertain significance	criteria provided, single submitter
4078731	NM_000810.4(GABRA5):c.472G>A (p.Asp158Asn)	GABRA5	Uncertain significance	criteria provided, single submitter
4078732	NM_000810.4(GABRA5):c.106A>C (p.Ser36Arg)	GABRA5	Uncertain significance	criteria provided, single submitter
4278280	NM_000810.4(GABRA5):c.309C>G (p.Ser103Arg)	GABRA5	Uncertain significance	criteria provided, single submitter
807199	NM_000810.4(GABRA5):c.713G>A (p.Ser238Asn)	GABRA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
983413	NM_000810.4(GABRA5):c.1166C>T (p.Pro389Leu)	GABRA5	Uncertain significance	criteria provided, single submitter
1221362	NM_000810.4(GABRA5):c.878-9C>A	GABRA5	Benign	criteria provided, multiple submitters, no conflicts
1252856	NM_000810.4(GABRA5):c.975C>T (p.Ala325=)	GABRA5	Benign	criteria provided, multiple submitters, no conflicts
1285288	NM_000810.4(GABRA5):c.606T>C (p.Val202=)	GABRA5	Benign	criteria provided, multiple submitters, no conflicts
1285289	NM_000810.4(GABRA5):c.878-27T>A	GABRA5	Benign	criteria provided, multiple submitters, no conflicts
734852	NM_000810.4(GABRA5):c.585G>A (p.Ala195=)	GABRA5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
GABRA5	Strong	Autosomal dominant	developmental and epileptic encephalopathy, 79	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GABRA5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
GABRA5	HGNC:4079	ENSG00000186297	P31644	Gamma-aminobutyric acid receptor subunit alpha-5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GABRA5	Gamma-aminobutyric acid receptor subunit alpha-5	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: 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)
GABRA5	Other/Unknown	no		GABAAa_rcpt, GABBAa5_rcpt, GABAA/Glycine_rcpt

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 10	1
nucleus accumbens	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GABRA5	141	broad	marker	nucleus accumbens, prefrontal cortex, Brodmann (1909) area 10

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GABRA5	1,907

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GABRA5	P31644	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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×	0.003	GABRA5

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
inner ear receptor cell development	1	2407.4×	0.003	GABRA5
innervation	1	887.0×	0.003	GABRA5
inhibitory synapse assembly	1	624.1×	0.003	GABRA5
gamma-aminobutyric acid signaling pathway	1	543.6×	0.003	GABRA5
synaptic transmission, GABAergic	1	495.6×	0.003	GABRA5
associative learning	1	481.5×	0.003	GABRA5
cochlea development	1	468.1×	0.003	GABRA5
behavioral fear response	1	432.1×	0.003	GABRA5
chloride transmembrane transport	1	237.3×	0.005	GABRA5
signal transduction	1	16.1×	0.062	GABRA5

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
GABRA5	ENZALUTAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GABRA5	27	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENZALUTAMIDE	4	GABRA5
DIAZEPAM	4	GABRA5
LIOTHYRONINE	4	GABRA5
GANAXOLONE	4	GABRA5
BREXANOLONE	4	GABRA5
APALUTAMIDE	4	GABRA5
FLUMAZENIL	4	GABRA5
CLONAZEPAM	4	GABRA5
FLUNITRAZEPAM	4	GABRA5
CHLORDIAZEPOXIDE	4	GABRA5
TRIAZOLAM	4	GABRA5
PROPOFOL	4	GABRA5
ALPRAZOLAM	4	GABRA5
DELORAZEPAM	2	GABRA5
FLAVONE	2	GABRA5
PROGABIDE	2	GABRA5
ABECARNIL	2	GABRA5
BAICALEIN	2	GABRA5
MK-0777	2	GABRA5
DARIGABAT	2	GABRA5
BRETAZENIL	2	GABRA5
BASMISANIL	2	GABRA5
AZD7325	2	GABRA5
SARIPIDEM	2	GABRA5
MUSCIMOL	1	GABRA5
GAMMA-AMINOBUTYRIC ACID	1	GABRA5
AZD6280	1	GABRA5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GABRA5	413	Binding:352, Functional:57, Toxicity:3, ADMET:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GABRA5	413

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

27 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)
ENZALUTAMIDE	4	GABRA5
DIAZEPAM	4	GABRA5
LIOTHYRONINE	4	GABRA5
GANAXOLONE	4	GABRA5
BREXANOLONE	4	GABRA5
APALUTAMIDE	4	GABRA5
FLUMAZENIL	4	GABRA5
CLONAZEPAM	4	GABRA5
FLUNITRAZEPAM	4	GABRA5
CHLORDIAZEPOXIDE	4	GABRA5
TRIAZOLAM	4	GABRA5
PROPOFOL	4	GABRA5
ALPRAZOLAM	4	GABRA5
DELORAZEPAM	2	GABRA5
FLAVONE	2	GABRA5
PROGABIDE	2	GABRA5
ABECARNIL	2	GABRA5
BAICALEIN	2	GABRA5
MK-0777	2	GABRA5
DARIGABAT	2	GABRA5
BRETAZENIL	2	GABRA5
BASMISANIL	2	GABRA5
AZD7325	2	GABRA5
SARIPIDEM	2	GABRA5
MUSCIMOL	1	GABRA5
GAMMA-AMINOBUTYRIC ACID	1	GABRA5
AZD6280	1	GABRA5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GABRA5
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.