Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
diseaseOn this page
Also known as autosomal dominant intellectual disability 8autosomal dominant non-syndromic intellectual disability caused by mutation in GRIN1GRIN1 autosomal dominant non-syndromic intellectual disabilityintellectual disability, autosomal dominant 8intellectual disability, autosomal dominant type 8mental retardation, autosomal dominant 8mental retardation, autosomal dominant 8, formerlymental retardation, autosomal dominant type 8MRD8NDHMSD
Summary
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (MONDO:0013655) is a disease caused by GRIN1 (GenCC Definitive), with 4 cohort genes.
At a glance
- Causal gene: GRIN1 (GenCC Definitive)
- Cohort genes: 4
- ClinVar variants: 1,031
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant |
| Mondo ID | MONDO:0013655 |
| OMIM | 614254 |
| DOID | DOID:0070038 |
| UMLS | C3280282 |
| MedGen | 481912 |
| GARD | 0013686 |
| Is cancer (heuristic) | no |
Also known as: autosomal dominant intellectual disability 8 · autosomal dominant non-syndromic intellectual disability caused by mutation in GRIN1 · GRIN1 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 8 · intellectual disability, autosomal dominant type 8 · mental retardation, autosomal dominant 8 · mental retardation, autosomal dominant 8, formerly · mental retardation, autosomal dominant type 8 · MRD8 · NDHMSD · neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
Data availability: 1,031 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76
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
600 retrieved; paginated sample, class counts are floors:
335 likely benign, 164 uncertain significance, 26 conflicting classifications of pathogenicity, 22 benign, 22 likely pathogenic, 21 pathogenic, 6 benign/likely benign, 4 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1076783 | NM_007327.4(GRIN1):c.1921A>G (p.Met641Val) | GRIN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1284989 | NM_007327.4(GRIN1):c.1976G>A (p.Arg659Gln) | GRIN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1329920 | NM_007327.4(GRIN1):c.1950C>A (p.Asn650Lys) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1445348 | NM_007327.4(GRIN1):c.2438T>C (p.Met813Thr) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1452432 | NM_007327.4(GRIN1):c.2443G>C (p.Gly815Arg) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1483551 | NM_007327.4(GRIN1):c.1324_1325dup (p.Ser443fs) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1484756 | NM_007327.4(GRIN1):c.529C>T (p.Gln177Ter) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1685863 | NM_007327.4(GRIN1):c.1668G>T (p.Gln556His) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1685864 | NM_007327.4(GRIN1):c.1832G>T (p.Trp611Leu) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1700197 | NM_007327.4(GRIN1):c.1921A>T (p.Met641Leu) | GRIN1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1713267 | NM_007327.4(GRIN1):c.1665G>T (p.Met555Ile) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1922738 | NM_007327.4(GRIN1):c.1069C>T (p.Gln357Ter) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 1949360 | NM_007327.4(GRIN1):c.1078A>T (p.Lys360Ter) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2000563 | NM_007327.4(GRIN1):c.2030_2034del (p.Asp677fs) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 208743 | NM_007327.4(GRIN1):c.2443G>A (p.Gly815Arg) | GRIN1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 209159 | NM_007327.4(GRIN1):c.1858G>C (p.Gly620Arg) | GRIN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2097493 | NM_007327.4(GRIN1):c.1798_1805del (p.Ala600fs) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2119508 | NM_007327.4(GRIN1):c.118C>T (p.Gln40Ter) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2147758 | NM_007327.4(GRIN1):c.268del (p.Ile90fs) | GRIN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2499551 | NM_007327.4(GRIN1):c.2451C>A (p.Phe817Leu) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2836372 | NM_007327.4(GRIN1):c.1736del (p.Leu579fs) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2866137 | NM_007327.4(GRIN1):c.1214A>T (p.Gln405Leu) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 2910238 | NM_007327.4(GRIN1):c.2365G>A (p.Asp789Asn) | GRIN1 | Pathogenic | criteria provided, single submitter |
| 29725 | NM_007327.4(GRIN1):c.1984G>A (p.Glu662Lys) | GRIN1 | Pathogenic | no assertion criteria provided |
| 29726 | NM_007327.4(GRIN1):c.1679_1681dup (p.Ser560dup) | GRIN1 | Pathogenic | no assertion criteria provided |
| 1333808 | NM_007327.4(GRIN1):c.1850C>T (p.Ser617Phe) | GRIN1 | Likely pathogenic | criteria provided, single submitter |
| 1481271 | NM_007327.4(GRIN1):c.2380C>G (p.Arg794Gly) | GRIN1 | Likely pathogenic | criteria provided, single submitter |
| 1679134 | NM_007327.4(GRIN1):c.1664T>C (p.Met555Thr) | GRIN1 | Likely pathogenic | criteria provided, single submitter |
| 1706588 | NM_007327.4(GRIN1):c.2377G>T (p.Val793Phe) | GRIN1 | Likely pathogenic | criteria provided, single submitter |
| 1710175 | NM_007327.4(GRIN1):c.2171+1G>A | GRIN1 | Likely pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · Orphanet: 5 · 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 | Definitive | Autosomal dominant | complex neurodevelopmental disorder | 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 |
| ABCA2 | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
Cohort genes → proteins
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GRIN1 | HGNC:4584 | ENSG00000176884 | Q05586 | Glutamate receptor ionotropic, NMDA 1 | gencc,clinvar |
| DPP7 | HGNC:14892 | ENSG00000176978 | Q9UHL4 | Dipeptidyl peptidase 2 | clinvar |
| ANAPC2 | HGNC:19989 | ENSG00000176248 | Q9UJX6 | Anaphase-promoting complex subunit 2 | clinvar |
| ABCA2 | HGNC:32 | ENSG00000107331 | Q9BZC7 | ATP-binding cassette sub-family A member 2 | 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+). |
| DPP7 | Dipeptidyl peptidase 2 | Plays an important role in the degradation of some oligopeptides. |
| ANAPC2 | Anaphase-promoting complex subunit 2 | Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of th… |
| ABCA2 | ATP-binding cassette sub-family A member 2 | Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Transporter | 1 | 19.4× | 0.151 |
| Protease | 1 | 9.2× | 0.157 |
| Other/Unknown | 2 | 0.9× | 0.769 |
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 | |
| DPP7 | Protease | yes | 3.4.14.2 | Peptidase_S28, AB_hydrolase_fold, Ser_carbopepase_S28_SKS |
| ANAPC2 | Other/Unknown | no | ANAPC2_C, Cullin_homology, Cullin_homology_sf | |
| ABCA2 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM |
Expression context
Cohort genes with no expression data: 0.
3 cohort genes 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) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right hemisphere of cerebellum | 4 |
| right uterine tube | 2 |
| cerebellar hemisphere | 1 |
| right frontal lobe | 1 |
| adenohypophysis | 1 |
| left testis | 1 |
| C1 segment of cervical spinal cord | 1 |
| spinal cord | 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 |
| DPP7 | 243 | ubiquitous | marker | adenohypophysis, right hemisphere of cerebellum, right uterine tube |
| ANAPC2 | 237 | ubiquitous | yes | right uterine tube, right hemisphere of cerebellum, left testis |
| ABCA2 | 234 | ubiquitous | marker | C1 segment of cervical spinal cord, spinal cord, right hemisphere of cerebellum |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ANAPC2 | 2,288 |
| ABCA2 | 1,678 |
| DPP7 | 1,078 |
| GRIN1 | 118 |
Structural data
PDB: 3 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| GRIN1 | Q05586 | 85 |
| ANAPC2 | Q9UJX6 | 23 |
| DPP7 | Q9UHL4 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ABCA2 | Q9BZC7 | 71.46 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 60. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components | 1 | 158.6× | 0.033 | ANAPC2 |
| ABC transporters in lipid homeostasis | 1 | 150.3× | 0.033 | ABCA2 |
| Ras activation upon Ca2+ influx through NMDA receptor | 1 | 142.8× | 0.033 | GRIN1 |
| Phosphorylation of the APC/C | 1 | 135.9× | 0.033 | ANAPC2 |
| Unblocking of NMDA receptors, glutamate binding and activation | 1 | 135.9× | 0.033 | GRIN1 |
| Synaptic adhesion-like molecules | 1 | 135.9× | 0.033 | GRIN1 |
| Negative regulation of NMDA receptor-mediated neuronal transmission | 1 | 135.9× | 0.033 | GRIN1 |
| Inactivation of APC/C via direct inhibition of the APC/C complex | 1 | 129.8× | 0.033 | ANAPC2 |
| Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 1 | 129.8× | 0.033 | ANAPC2 |
| Aberrant regulation of mitotic exit in cancer due to RB1 defects | 1 | 129.8× | 0.033 | ANAPC2 |
| Long-term potentiation | 1 | 119.0× | 0.033 | GRIN1 |
| APC/C:Cdc20 mediated degradation of Cyclin B | 1 | 114.2× | 0.033 | ANAPC2 |
| APC-Cdc20 mediated degradation of Nek2A | 1 | 105.7× | 0.033 | ANAPC2 |
| APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint | 1 | 105.7× | 0.033 | ANAPC2 |
| Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 1 | 102.0× | 0.033 | ANAPC2 |
| Aberrant regulation of mitotic cell cycle due to RB1 defects | 1 | 102.0× | 0.033 | ANAPC2 |
| Diseases of mitotic cell cycle | 1 | 98.5× | 0.033 | ANAPC2 |
| APC/C:Cdc20 mediated degradation of mitotic proteins | 1 | 89.2× | 0.033 | ANAPC2 |
| APC/C-mediated degradation of cell cycle proteins | 1 | 84.0× | 0.033 | ANAPC2 |
| Regulation of mitotic cell cycle | 1 | 84.0× | 0.033 | ANAPC2 |
| DNA Replication Pre-Initiation | 1 | 79.3× | 0.033 | ANAPC2 |
| Regulation of APC/C activators between G1/S and early anaphase | 1 | 77.2× | 0.033 | ANAPC2 |
| Switching of origins to a post-replicative state | 1 | 75.1× | 0.033 | ANAPC2 |
| Synthesis of DNA | 1 | 75.1× | 0.033 | ANAPC2 |
| EPHB-mediated forward signaling | 1 | 66.4× | 0.035 | GRIN1 |
| Transcriptional Regulation by VENTX | 1 | 66.4× | 0.035 | ANAPC2 |
| Assembly and cell surface presentation of NMDA receptors | 1 | 63.4× | 0.035 | GRIN1 |
| DNA Replication | 1 | 59.5× | 0.036 | ANAPC2 |
| Neurexins and neuroligins | 1 | 49.2× | 0.040 | GRIN1 |
| Autodegradation of Cdh1 by Cdh1:APC/C | 1 | 47.6× | 0.040 | ANAPC2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| propylene metabolic process | 1 | 4213.0× | 0.003 | GRIN1 |
| negative regulation of intracellular cholesterol transport | 1 | 4213.0× | 0.003 | ABCA2 |
| negative regulation of phospholipid biosynthetic process | 1 | 4213.0× | 0.003 | ABCA2 |
| negative regulation of sphingolipid biosynthetic process | 1 | 4213.0× | 0.003 | ABCA2 |
| regulation of protein localization to cell periphery | 1 | 4213.0× | 0.003 | ABCA2 |
| response to glycine | 1 | 4213.0× | 0.003 | GRIN1 |
| negative regulation of steroid metabolic process | 1 | 2106.5× | 0.003 | ABCA2 |
| ceramide translocation | 1 | 2106.5× | 0.003 | ABCA2 |
| regulation of post-translational protein modification | 1 | 2106.5× | 0.003 | ABCA2 |
| negative regulation of receptor-mediated endocytosis involved in cholesterol transport | 1 | 2106.5× | 0.003 | ABCA2 |
| positive regulation of low-density lipoprotein particle receptor catabolic process | 1 | 1404.3× | 0.005 | ABCA2 |
| ganglioside metabolic process | 1 | 1053.2× | 0.005 | ABCA2 |
| regulation of intracellular cholesterol transport | 1 | 1053.2× | 0.005 | ABCA2 |
| sphingomyelin metabolic process | 1 | 842.6× | 0.005 | ABCA2 |
| positive regulation of amyloid precursor protein biosynthetic process | 1 | 842.6× | 0.005 | ABCA2 |
| intracellular sphingolipid homeostasis | 1 | 842.6× | 0.005 | ABCA2 |
| negative regulation of cholesterol efflux | 1 | 702.2× | 0.006 | ABCA2 |
| glycosphingolipid metabolic process | 1 | 601.9× | 0.006 | ABCA2 |
| regulation of steroid metabolic process | 1 | 601.9× | 0.006 | ABCA2 |
| central nervous system myelin formation | 1 | 601.9× | 0.006 | ABCA2 |
| metaphase/anaphase transition of mitotic cell cycle | 1 | 526.6× | 0.006 | ANAPC2 |
| regulation of monoatomic cation transmembrane transport | 1 | 526.6× | 0.006 | GRIN1 |
| positive regulation of synapse maturation | 1 | 468.1× | 0.007 | ANAPC2 |
| response to cholesterol | 1 | 421.3× | 0.007 | ABCA2 |
| positive regulation of amyloid precursor protein catabolic process | 1 | 421.3× | 0.007 | ABCA2 |
| regulation of protein localization to cell surface | 1 | 421.3× | 0.007 | ABCA2 |
| positive regulation of synaptic plasticity | 1 | 383.0× | 0.007 | ANAPC2 |
| calcium ion transmembrane import into cytosol | 1 | 383.0× | 0.007 | GRIN1 |
| ionotropic glutamate receptor signaling pathway | 1 | 324.1× | 0.008 | GRIN1 |
| excitatory chemical synaptic transmission | 1 | 324.1× | 0.008 | GRIN1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2
Druggability breadth: 2 of 4 evidence-associated genes (50%) 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 |
| DPP7 | SITAGLIPTIN |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| GRIN1 | 39 | 4 |
| DPP7 | 3 | 4 |
| ANAPC2 | 0 | 0 |
| ABCA2 | 0 | 0 |
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 |
| SITAGLIPTIN | 4 | DPP7 |
| GOSOGLIPTIN | 4 | DPP7 |
| ESMETHADONE | 3 | GRIN1 |
| DALZANEMDOR | 3 | GRIN1 |
| LATREPIRDINE | 3 | GRIN1 |
| GLUTAMIC ACID | 3 | GRIN1 |
| TALABOSTAT | 3 | DPP7 |
| 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 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| GRIN1 | 481 | Binding:435, Functional:40, ADMET:5, Toxicity:1 |
| DPP7 | 147 | Binding:142, Functional:4, ADMET:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| DPP7 | 3.4.14.2 | dipeptidyl-peptidase II |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| GRIN1 | 481 |
| DPP7 | 147 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; 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 |
| SITAGLIPTIN | 4 | DPP7 |
| GOSOGLIPTIN | 4 | DPP7 |
| ESMETHADONE | 3 | GRIN1 |
| DALZANEMDOR | 3 | GRIN1 |
| LATREPIRDINE | 3 | GRIN1 |
| GLUTAMIC ACID | 3 | GRIN1 |
| TALABOSTAT | 3 | DPP7 |
| 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 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | GRIN1, DPP7 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | ABCA2 |
| E | Difficult family or no structure, no drug | 1 | ANAPC2 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ANAPC2 | 0 | — |
| ABCA2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.