Developmental and epileptic encephalopathy 101

disease

On this page

Also known as DEE101

Summary

Developmental and epileptic encephalopathy 101 (MONDO:0030727) is a disease caused by GRIN1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: GRIN1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 101
Mondo ID	MONDO:0030727
OMIM	619814
DOID	DOID:0070387
UMLS	C5676955
MedGen	1805172
GARD	0025626
Is cancer (heuristic)	no

Also known as: DEE101 · developmental and epileptic encephalopathy 101

Data availability: 11 ClinVar variants · 1 GenCC gene-disease record.

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 101

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

11 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1525992	NM_007327.4(GRIN1):c.394-1G>C	GRIN1	Pathogenic	no assertion criteria provided
1700197	NM_007327.4(GRIN1):c.1921A>T (p.Met641Leu)	GRIN1	Pathogenic	criteria provided, multiple submitters, no conflicts
3024338	NM_007327.4(GRIN1):c.1904T>G (p.Val635Gly)	GRIN1	Pathogenic	criteria provided, single submitter
487503	NM_007327.4(GRIN1):c.2479G>A (p.Gly827Arg)	GRIN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
487506	NM_007327.4(GRIN1):c.1666C>T (p.Gln556Ter)	GRIN1	Pathogenic	no assertion criteria provided
3382998	NM_007327.4(GRIN1):c.1975C>G (p.Arg659Gly)	GRIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625956	NM_007327.4(GRIN1):c.957G>A (p.Pro319=)	GRIN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2431427	NM_007327.4(GRIN1):c.1237C>A (p.Pro413Thr)	GRIN1	Uncertain significance	criteria provided, single submitter
3893157	NM_007327.4(GRIN1):c.1387C>T (p.Leu463Phe)	GRIN1	Uncertain significance	criteria provided, single submitter
625954	NM_007327.4(GRIN1):c.734A>T (p.Tyr245Phe)	GRIN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
387537	NM_007327.4(GRIN1):c.394-4G>A	GRIN1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
GRIN1	Strong	Autosomal recessive	developmental and epileptic encephalopathy 101	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRIN1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
GRIN1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
GRIN1	Orphanet:208447	Bilateral generalized polymicrogyria
GRIN1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
GRIN1	HGNC:4584	ENSG00000176884	Q05586	Glutamate receptor ionotropic, NMDA 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRIN1	Glutamate receptor ionotropic, NMDA 1	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).

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)
GRIN1	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_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
cerebellar hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRIN1	215	tissue_specific	marker	right hemisphere of cerebellum, right frontal lobe, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRIN1	118

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRIN1	Q05586	85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.004	GRIN1
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.004	GRIN1
Synaptic adhesion-like molecules	1	543.8×	0.004	GRIN1
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.004	GRIN1
Long-term potentiation	1	475.8×	0.004	GRIN1
EPHB-mediated forward signaling	1	265.6×	0.005	GRIN1
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.005	GRIN1
Neurexins and neuroligins	1	196.9×	0.006	GRIN1
RAF/MAP kinase cascade	1	61.1×	0.016	GRIN1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
propylene metabolic process	1	16852.0×	7e-04	GRIN1
response to glycine	1	16852.0×	7e-04	GRIN1
regulation of monoatomic cation transmembrane transport	1	2106.5×	0.003	GRIN1
calcium ion transmembrane import into cytosol	1	1532.0×	0.003	GRIN1
ionotropic glutamate receptor signaling pathway	1	1296.3×	0.003	GRIN1
excitatory chemical synaptic transmission	1	1296.3×	0.003	GRIN1
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.003	GRIN1
positive regulation of reactive oxygen species biosynthetic process	1	1123.5×	0.003	GRIN1
protein heterotetramerization	1	1053.2×	0.003	GRIN1
monoatomic cation transport	1	766.0×	0.003	GRIN1
regulation of neuronal synaptic plasticity	1	674.1×	0.003	GRIN1
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.003	GRIN1
monoatomic cation transmembrane transport	1	624.1×	0.003	GRIN1
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	GRIN1
calcium ion homeostasis	1	443.5×	0.004	GRIN1
excitatory postsynaptic potential	1	443.5×	0.004	GRIN1
visual learning	1	306.4×	0.005	GRIN1
regulation of synaptic plasticity	1	259.3×	0.005	GRIN1
regulation of membrane potential	1	230.8×	0.006	GRIN1
calcium ion transmembrane transport	1	210.7×	0.006	GRIN1
sodium ion transmembrane transport	1	203.0×	0.006	GRIN1
response to ethanol	1	146.5×	0.008	GRIN1
brain development	1	79.5×	0.013	GRIN1
chemical synaptic transmission	1	77.3×	0.013	GRIN1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	GRIN1

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
GRIN1	DEXTROMETHORPHAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIN1	39	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DEXTROMETHORPHAN	4	GRIN1
KETAMINE	4	GRIN1
CYCLOSERINE	4	GRIN1
MEMANTINE	4	GRIN1
TACRINE	4	GRIN1
MEMANTINE HYDROCHLORIDE	4	GRIN1
ESKETAMINE	4	GRIN1
PENTAMIDINE	4	GRIN1
AMANTADINE	4	GRIN1
LEVORPHANOL	4	GRIN1
CHLORPROMAZINE	4	GRIN1
PROCYCLIDINE	4	GRIN1
ORPHENADRINE	4	GRIN1
ESMETHADONE	3	GRIN1
DALZANEMDOR	3	GRIN1
LATREPIRDINE	3	GRIN1
GLUTAMIC ACID	3	GRIN1
DEXTRORPHAN	2	GRIN1
LEVOMETHADONE	2	GRIN1
ALPHAMETHADOL	2	GRIN1
TRAXOPRODIL	2	GRIN1
RADIPRODIL	2	GRIN1
PHENCYCLIDINE	2	GRIN1
DIZOCILPINE	2	GRIN1
ELIPRODIL	2	GRIN1
IFENPRODIL	2	GRIN1
ONFASPRODIL	2	GRIN1
DEXOXADROL	2	GRIN1
BETAMETHADOL	2	GRIN1
DIMEMORFAN	2	GRIN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRIN1	481	Binding:435, Functional:40, ADMET:5, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GRIN1	481

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)
DEXTROMETHORPHAN	4	GRIN1
KETAMINE	4	GRIN1
CYCLOSERINE	4	GRIN1
MEMANTINE	4	GRIN1
TACRINE	4	GRIN1
MEMANTINE HYDROCHLORIDE	4	GRIN1
ESKETAMINE	4	GRIN1
PENTAMIDINE	4	GRIN1
AMANTADINE	4	GRIN1
LEVORPHANOL	4	GRIN1
CHLORPROMAZINE	4	GRIN1
PROCYCLIDINE	4	GRIN1
ORPHENADRINE	4	GRIN1
ESMETHADONE	3	GRIN1
DALZANEMDOR	3	GRIN1
LATREPIRDINE	3	GRIN1
GLUTAMIC ACID	3	GRIN1
DEXTRORPHAN	2	GRIN1
LEVOMETHADONE	2	GRIN1
ALPHAMETHADOL	2	GRIN1
TRAXOPRODIL	2	GRIN1
RADIPRODIL	2	GRIN1
PHENCYCLIDINE	2	GRIN1
DIZOCILPINE	2	GRIN1
ELIPRODIL	2	GRIN1
IFENPRODIL	2	GRIN1
ONFASPRODIL	2	GRIN1
DEXOXADROL	2	GRIN1
BETAMETHADOL	2	GRIN1
DIMEMORFAN	2	GRIN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRIN1
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.

Cohort genes: GRIN1