Intellectual developmental disorder, autosomal recessive 76

Summary

Intellectual developmental disorder, autosomal recessive 76 (MONDO:0030968) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 76
Mondo ID	MONDO:0030968
OMIM	619931
DOID	DOID:0081235
UMLS	C5677007
MedGen	1808571
GARD	0025669
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, autosomal recessive 76 · mental retardation, autosomal recessive 76 · MRT76

Data availability: 3 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 76

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1693467	NM_000827.4(GRIA1):c.1129C>T (p.Arg377Ter)	GRIA1	Pathogenic	criteria provided, single submitter
39966	NM_000827.4(GRIA1):c.1906G>A (p.Ala636Thr)	GRIA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3731284	NM_000827.4(GRIA1):c.1151A>C (p.Glu384Ala)	GRIA1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
GRIA1	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 67	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRIA1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
GRIA1	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
GRIA1	HGNC:4571	ENSG00000155511	P42261	Glutamate receptor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRIA1	Glutamate receptor 1	Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid.

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)
GRIA1	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
CA1 field of hippocampus	1
cortical plate	1
cranial nerve II	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRIA1	194	broad	marker	CA1 field of hippocampus, cortical plate, cranial nerve II

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRIA1	3,443

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRIA1	P42261	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Activation of AMPA receptors	1	2855.0×	0.003	GRIA1
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.003	GRIA1
Trafficking of AMPA receptors	1	543.8×	0.003	GRIA1
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.003	GRIA1
Synaptic adhesion-like molecules	1	543.8×	0.003	GRIA1
Long-term potentiation	1	475.8×	0.003	GRIA1
Cargo concentration in the ER	1	335.9×	0.003	GRIA1
COPII-mediated vesicle transport	1	163.1×	0.006	GRIA1

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
response to lithium ion	1	8426.0×	0.001	GRIA1
positive regulation of locomotion involved in locomotory behavior	1	8426.0×	0.001	GRIA1
cellular response to amine stimulus	1	5617.3×	0.001	GRIA1
response to sucrose	1	3370.4×	0.001	GRIA1
cellular response to ammonium ion	1	3370.4×	0.001	GRIA1
cellular response to dsRNA	1	3370.4×	0.001	GRIA1
response to psychosocial stress	1	3370.4×	0.001	GRIA1
regulation of receptor recycling	1	2808.7×	0.001	GRIA1
positive regulation of membrane potential	1	2808.7×	0.001	GRIA1
response to fungicide	1	2808.7×	0.001	GRIA1
cellular response to brain-derived neurotrophic factor stimulus	1	1872.4×	0.002	GRIA1
cellular response to L-glutamate	1	1685.2×	0.002	GRIA1
conditioned place preference	1	1685.2×	0.002	GRIA1
response to morphine	1	1203.7×	0.002	GRIA1
response to arsenic-containing substance	1	1203.7×	0.002	GRIA1
behavioral response to pain	1	887.0×	0.003	GRIA1
long-term synaptic depression	1	887.0×	0.003	GRIA1
cellular response to peptide hormone stimulus	1	842.6×	0.003	GRIA1
regulation of monoatomic ion transmembrane transport	1	732.7×	0.003	GRIA1
response to electrical stimulus	1	648.1×	0.003	GRIA1
response to cocaine	1	581.1×	0.003	GRIA1
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	GRIA1
spinal cord development	1	510.7×	0.003	GRIA1
neuronal action potential	1	481.5×	0.003	GRIA1
long-term memory	1	421.3×	0.004	GRIA1
response to nutrient levels	1	366.4×	0.004	GRIA1
synaptic transmission, glutamatergic	1	358.6×	0.004	GRIA1
receptor internalization	1	324.1×	0.004	GRIA1
long-term synaptic potentiation	1	280.9×	0.005	GRIA1
synapse assembly	1	230.8×	0.005	GRIA1

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
GRIA1	PERAMPANEL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIA1	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PERAMPANEL	4	GRIA1
CYCLOTHIAZIDE	4	GRIA1
GLUTAMIC ACID	3	GRIA1
TEZAMPANEL ANHYDROUS	2	GRIA1
KAINIC ACID	2	GRIA1
SELFOTEL	2	GRIA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRIA1	168	Binding:127, Functional:39, ADMET:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GRIA1	168

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

6 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)
PERAMPANEL	4	GRIA1
CYCLOTHIAZIDE	4	GRIA1
GLUTAMIC ACID	3	GRIA1
TEZAMPANEL ANHYDROUS	2	GRIA1
KAINIC ACID	2	GRIA1
SELFOTEL	2	GRIA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRIA1
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.