GRIN2B-related complex neurodevelopmental disorder

Summary

GRIN2B-related complex neurodevelopmental disorder (MONDO:0700350) is a disease caused by GRIN2B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GRIN2B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	GRIN2B-related complex neurodevelopmental disorder
Mondo ID	MONDO:0700350
GARD	0028024
Is cancer (heuristic)	no

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

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › complex neurodevelopmental disorder › GRIN-related complex neurodevelopmental disorder › GRIN2B-related complex neurodevelopmental disorder

Related subtypes (3): developmental and epileptic encephalopathy, 46, GRIN1-related complex neurodevelopmental disorder, GRIN2A-related complex neurodevelopmental disorder

Subtypes (2): intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
435389	NM_000834.5(GRIN2B):c.1946A>G (p.Asn649Ser)	GRIN2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
GRIN2B	Definitive	Autosomal dominant	complex neurodevelopmental disorder	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRIN2B	Orphanet:589547	GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder
GRIN2B	Orphanet:697160	Infantile epileptic spasms syndrome

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
GRIN2B	HGNC:4586	ENSG00000273079	Q13224	Glutamate receptor ionotropic, NMDA 2B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRIN2B	Glutamate receptor ionotropic, NMDA 2B	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)
GRIN2B	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
Brodmann (1909) area 23	1
buccal mucosa cell	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRIN2B	138	broad	marker	buccal mucosa cell, cortical plate, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRIN2B	3,611

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRIN2B	Q13224	36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Activated NTRK2 signals through FYN	1	1903.3×	0.003	GRIN2B
MECP2 regulates neuronal receptors and channels	1	601.0×	0.003	GRIN2B
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.003	GRIN2B
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.003	GRIN2B
Synaptic adhesion-like molecules	1	543.8×	0.003	GRIN2B
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.003	GRIN2B
Long-term potentiation	1	475.8×	0.003	GRIN2B
EPHB-mediated forward signaling	1	265.6×	0.005	GRIN2B
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.005	GRIN2B
Neurexins and neuroligins	1	196.9×	0.006	GRIN2B
RAF/MAP kinase cascade	1	61.1×	0.016	GRIN2B

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
negative regulation of dendritic spine maintenance	1	2808.7×	0.003	GRIN2B
regulation of monoatomic cation transmembrane transport	1	2106.5×	0.003	GRIN2B
calcium ion transmembrane import into cytosol	1	1532.0×	0.003	GRIN2B
ionotropic glutamate receptor signaling pathway	1	1296.3×	0.003	GRIN2B
excitatory chemical synaptic transmission	1	1296.3×	0.003	GRIN2B
protein heterotetramerization	1	1053.2×	0.003	GRIN2B
glutamate receptor signaling pathway	1	936.2×	0.003	GRIN2B
regulation of neuronal synaptic plasticity	1	674.1×	0.003	GRIN2B
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.003	GRIN2B
monoatomic cation transmembrane transport	1	624.1×	0.003	GRIN2B
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	GRIN2B
excitatory postsynaptic potential	1	443.5×	0.004	GRIN2B
synaptic transmission, glutamatergic	1	358.6×	0.004	GRIN2B
long-term synaptic potentiation	1	280.9×	0.005	GRIN2B
regulation of synaptic plasticity	1	259.3×	0.005	GRIN2B
learning or memory	1	240.7×	0.005	GRIN2B
response to ethanol	1	146.5×	0.008	GRIN2B
brain development	1	79.5×	0.013	GRIN2B
chemical synaptic transmission	1	77.3×	0.013	GRIN2B

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
GRIN2B	HALOPERIDOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIN2B	35	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
HALOPERIDOL	4	GRIN2B
DEXTROMETHORPHAN	4	GRIN2B
KETAMINE	4	GRIN2B
CYCLOSERINE	4	GRIN2B
MEMANTINE	4	GRIN2B
TACRINE	4	GRIN2B
LEVORPHANOL	4	GRIN2B
AMANTADINE	4	GRIN2B
CHLORPROMAZINE	4	GRIN2B
PROCYCLIDINE	4	GRIN2B
ORPHENADRINE	4	GRIN2B
DALZANEMDOR	3	GRIN2B
LATREPIRDINE	3	GRIN2B
ESMETHADONE	3	GRIN2B
GLUTAMIC ACID	3	GRIN2B
TRAXOPRODIL	2	GRIN2B
ELIPRODIL	2	GRIN2B
IFENPRODIL	2	GRIN2B
EVT-101 FREE BASE	2	GRIN2B
ZELQUISTINEL	2	GRIN2B
DEXTRORPHAN	2	GRIN2B
LEVOMETHADONE	2	GRIN2B
ALPHAMETHADOL	2	GRIN2B
RADIPRODIL	2	GRIN2B
PHENCYCLIDINE	2	GRIN2B
DIZOCILPINE	2	GRIN2B
ONFASPRODIL	2	GRIN2B
TEZAMPANEL ANHYDROUS	2	GRIN2B
RACEMETHORPHAN	2	GRIN2B
LICOSTINEL	2	GRIN2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRIN2B	471	Binding:429, Functional:36, 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
GRIN2B	471

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)
HALOPERIDOL	4	GRIN2B
DEXTROMETHORPHAN	4	GRIN2B
KETAMINE	4	GRIN2B
CYCLOSERINE	4	GRIN2B
MEMANTINE	4	GRIN2B
TACRINE	4	GRIN2B
LEVORPHANOL	4	GRIN2B
AMANTADINE	4	GRIN2B
CHLORPROMAZINE	4	GRIN2B
PROCYCLIDINE	4	GRIN2B
ORPHENADRINE	4	GRIN2B
DALZANEMDOR	3	GRIN2B
LATREPIRDINE	3	GRIN2B
ESMETHADONE	3	GRIN2B
GLUTAMIC ACID	3	GRIN2B
TRAXOPRODIL	2	GRIN2B
ELIPRODIL	2	GRIN2B
IFENPRODIL	2	GRIN2B
EVT-101 FREE BASE	2	GRIN2B
ZELQUISTINEL	2	GRIN2B
DEXTRORPHAN	2	GRIN2B
LEVOMETHADONE	2	GRIN2B
ALPHAMETHADOL	2	GRIN2B
RADIPRODIL	2	GRIN2B
PHENCYCLIDINE	2	GRIN2B
DIZOCILPINE	2	GRIN2B
ONFASPRODIL	2	GRIN2B
TEZAMPANEL ANHYDROUS	2	GRIN2B
RACEMETHORPHAN	2	GRIN2B
LICOSTINEL	2	GRIN2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRIN2B
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.