Developmental and epileptic encephalopathy, 17

disease

On this page

Also known as DEE17developmental and epileptic encephalopathy 17early infantile epileptic encephalopathy caused by mutation in GNAO1early infantile epileptic encephalopathy-17EIEE17epileptic encephalopathy, early infantile, 17epileptic encephalopathy, early infantile, type 17GNAO1 early infantile epileptic encephalopathyGNAO1 encephalopathy

Summary

Developmental and epileptic encephalopathy, 17 (MONDO:0014199) is a disease caused by GNAO1 (GenCC Definitive), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include zinc acetate.

At a glance

Causal gene: GNAO1 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 67
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 17
Mondo ID	MONDO:0014199
OMIM	615473
DOID	DOID:0080450
UMLS	C3809606
MedGen	815936
GARD	0013378
Is cancer (heuristic)	no

Also known as: DEE17 · developmental and epileptic encephalopathy 17 · early infantile epileptic encephalopathy caused by mutation in GNAO1 · early infantile epileptic encephalopathy-17 · EIEE17 · epileptic encephalopathy, early infantile, 17 · epileptic encephalopathy, early infantile, type 17 · GNAO1 early infantile epileptic encephalopathy · GNAO1 encephalopathy

Data availability: 67 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, 17

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

67 retrieved; paginated sample, class counts are floors:

20 pathogenic, 17 uncertain significance, 14 likely pathogenic, 8 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012170	NM_020988.3(GNAO1):c.136A>G (p.Lys46Glu)	GNAO1	Pathogenic	criteria provided, single submitter
1012172	NM_020988.3(GNAO1):c.470T>C (p.Leu157Pro)	GNAO1	Pathogenic	criteria provided, single submitter
1012173	NM_020988.3(GNAO1):c.810C>A (p.Asn270Lys)	GNAO1	Pathogenic	criteria provided, single submitter
1374497	NM_020988.3(GNAO1):c.124G>A (p.Gly42Arg)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
1685853	NM_020988.3(GNAO1):c.610G>C (p.Gly204Arg)	GNAO1	Pathogenic	criteria provided, single submitter
1685854	NM_020988.3(GNAO1):c.620C>T (p.Ser207Phe)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802165	NM_020988.3(GNAO1):c.17G>T (p.Ser6Ile)	GNAO1	Pathogenic	no assertion criteria provided
1802972	NM_020988.3(GNAO1):c.119G>C (p.Gly40Ala)	GNAO1	Pathogenic	no assertion criteria provided
208677	NM_020988.3(GNAO1):c.626G>A (p.Arg209His)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
211088	NM_020988.3(GNAO1):c.680C>T (p.Ala227Val)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265350	NM_020988.3(GNAO1):c.625C>T (p.Arg209Cys)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
280526	NM_020988.3(GNAO1):c.118G>T (p.Gly40Trp)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
2824114	NM_020988.3(GNAO1):c.133G>T (p.Gly45Ter)	GNAO1	Pathogenic	criteria provided, single submitter
3235074	NM_020988.3(GNAO1):c.1054G>A (p.Gly352Ser)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3572883	NM_020988.3(GNAO1):c.510del (p.Thr171fs)	GNAO1	Pathogenic	criteria provided, single submitter
374381	NM_020988.3(GNAO1):c.692A>G (p.Tyr231Cys)	GNAO1	Pathogenic	criteria provided, single submitter
420523	NM_020988.3(GNAO1):c.709G>A (p.Glu237Lys)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
426965	NM_020988.3(GNAO1):c.724-8G>A	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
431699	NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
435341	NM_020988.3(GNAO1):c.143C>T (p.Thr48Ile)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
496687	NM_020988.3(GNAO1):c.851T>C (p.Leu284Ser)	GNAO1	Pathogenic	criteria provided, single submitter
641655	NM_020988.3(GNAO1):c.140G>A (p.Ser47Asn)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
66112	NM_020988.3(GNAO1):c.836T>A (p.Ile279Asn)	GNAO1	Pathogenic	no assertion criteria provided
66113	NM_020988.3(GNAO1):c.521A>G (p.Asp174Gly)	GNAO1	Pathogenic	criteria provided, single submitter
66114	NM_020988.3(GNAO1):c.572_592del (p.Thr191_Phe197del)	GNAO1	Pathogenic	no assertion criteria provided
66115	NM_020988.3(GNAO1):c.607G>A (p.Gly203Arg)	GNAO1	Pathogenic	criteria provided, multiple submitters, no conflicts
666297	NM_020988.3(GNAO1):c.118G>A (p.Gly40Arg)	GNAO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
803257	NM_020988.3(GNAO1):c.607G>C (p.Gly203Arg)	GNAO1	Pathogenic	criteria provided, single submitter
1012171	NM_020988.3(GNAO1):c.687C>G (p.Ser229Arg)	GNAO1	Likely pathogenic	criteria provided, single submitter
1012174	NM_020988.3(GNAO1):c.817G>T (p.Asp273Tyr)	GNAO1	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
GNAO1	Definitive	Autosomal dominant	genetic developmental and epileptic encephalopathy	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNAO1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
GNAO1	Orphanet:592564	GNAO1-related developmental delay-seizures-movement disorder spectrum

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
GNAO1	HGNC:4389	ENSG00000087258	P09471	Guanine nucleotide-binding protein G(o) subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNAO1	Guanine nucleotide-binding protein G(o) subunit alpha	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

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)
GNAO1	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert

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
cortical plate	1
entorhinal cortex	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNAO1	261	broad	marker	cortical plate, superficial temporal artery, entorhinal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAO1	3,437

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAO1	P09471	86

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
Ca2+ pathway	1	178.4×	0.006	GNAO1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
G protein-coupled dopamine receptor signaling pathway	1	1872.4×	0.003	GNAO1
adenylate cyclase-inhibiting serotonin receptor signaling pathway	1	1685.2×	0.003	GNAO1
obsolete vesicle docking involved in exocytosis	1	674.1×	0.003	GNAO1
postsynaptic modulation of chemical synaptic transmission	1	674.1×	0.003	GNAO1
regulation of heart contraction	1	495.6×	0.003	GNAO1
negative regulation of insulin secretion	1	495.6×	0.003	GNAO1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	337.0×	0.004	GNAO1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	218.9×	0.005	GNAO1
muscle contraction	1	208.1×	0.005	GNAO1
locomotory behavior	1	179.3×	0.006	GNAO1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNAO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GNAO1	12	Functional:10, Binding:2

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	GNAO1

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)
GNAO1	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ZINC ACETATE	4	1

Cohort genes: GNAO1
Drugs: Zinc Acetate