Adams-Oliver syndrome 5
diseaseOn this page
Also known as Adams-Oliver syndrome caused by mutation in NOTCH1Adams-Oliver syndrome type 5AOS5
Summary
Adams-Oliver syndrome 5 (MONDO:0014459) is a disease caused by NOTCH1 (GenCC Definitive), with 9 cohort genes.
At a glance
- Causal gene: NOTCH1 (GenCC Definitive)
- Cohort genes: 9
- ClinVar variants: 3,448
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Adams-Oliver syndrome 5 |
| Mondo ID | MONDO:0014459 |
| OMIM | 616028 |
| UMLS | C4014970 |
| MedGen | 863407 |
| GARD | 0016049 |
| Is cancer (heuristic) | no |
Also known as: Adams-Oliver syndrome 5 · Adams-Oliver syndrome caused by mutation in NOTCH1 · Adams-Oliver syndrome caused by mutation in Notch1 · Adams-Oliver syndrome type 5 · AOS5
Data availability: 3,448 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Adams-Oliver syndrome › Adams-Oliver syndrome 5
Related subtypes (5): Adams-Oliver syndrome 2, Adams-Oliver syndrome 3, Adams-Oliver syndrome 4, Adams-Oliver syndrome 6, Adams-Oliver syndrome 1
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:
196 likely benign, 186 uncertain significance, 146 conflicting classifications of pathogenicity, 36 benign/likely benign, 23 benign, 9 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1072334 | NM_017617.5(NOTCH1):c.4363C>T (p.Gln1455Ter) | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 1074216 | NM_017617.5(NOTCH1):c.4396C>T (p.Gln1466Ter) | NOTCH1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1075050 | NM_017617.5(NOTCH1):c.1784_1787del (p.Tyr595fs) | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 12476 | NM_017617.5(NOTCH1):c.3319C>T (p.Arg1107Ter) | NOTCH1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12477 | NM_017617.5(NOTCH1):c.4512del (p.Cys1505fs) | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 1409179 | NM_017617.5(NOTCH1):c.1800_1801dup (p.Glu601fs) | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 1428655 | NM_017617.5(NOTCH1):c.428del (p.Pro143fs) | NOTCH1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1452411 | NM_017617.5(NOTCH1):c.4483C>T (p.Gln1495Ter) | NOTCH1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1453811 | NM_017617.5(NOTCH1):c.763_773del (p.Glu255fs) | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 1456559 | NC_000009.11:g.(?139404165)(139405277_?)del | NOTCH1 | Pathogenic | criteria provided, single submitter |
| 1471980 | NM_017617.5(NOTCH1):c.2015-2del | NOTCH1 | Likely pathogenic | criteria provided, single submitter |
| 1504992 | NM_017617.5(NOTCH1):c.2319_2354-74del | NOTCH1 | Likely pathogenic | criteria provided, single submitter |
| 1000120 | NM_017617.5(NOTCH1):c.3724G>A (p.Gly1242Ser) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1000234 | NM_017617.5(NOTCH1):c.7114C>T (p.Arg2372Trp) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1000697 | NM_017617.5(NOTCH1):c.6739C>G (p.Leu2247Val) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1001513 | NM_017617.5(NOTCH1):c.1384C>G (p.Gln462Glu) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1001892 | NM_017617.5(NOTCH1):c.230T>G (p.Val77Gly) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1006482 | NM_017617.5(NOTCH1):c.3579G>T (p.Gln1193His) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1011208 | NM_017617.5(NOTCH1):c.7382G>T (p.Ser2461Ile) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1014759 | NM_017617.5(NOTCH1):c.2002C>G (p.Pro668Ala) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1019643 | NM_017617.5(NOTCH1):c.3404C>T (p.Ala1135Val) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1023083 | NM_017617.5(NOTCH1):c.700C>T (p.Arg234Cys) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1025041 | NM_017617.5(NOTCH1):c.3905G>A (p.Arg1302His) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1026412 | NM_017617.5(NOTCH1):c.7157A>G (p.Gln2386Arg) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1029477 | NM_017617.5(NOTCH1):c.2153A>G (p.Asn718Ser) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1033431 | NM_017617.5(NOTCH1):c.1256-15G>A | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1035741 | NM_017617.5(NOTCH1):c.7126C>A (p.Gln2376Lys) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1036234 | NM_017617.5(NOTCH1):c.5573T>C (p.Met1858Thr) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1036564 | NM_017617.5(NOTCH1):c.4865G>A (p.Arg1622His) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1036675 | NM_017617.5(NOTCH1):c.2995G>A (p.Val999Met) | NOTCH1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · Orphanet: 10 · 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 |
|---|---|---|---|---|
| NOTCH1 | Definitive | Autosomal dominant | Adams-Oliver syndrome | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| NOTCH1 | Orphanet:402075 | Familial bicuspid aortic valve |
| NOTCH1 | Orphanet:974 | Adams-Oliver syndrome |
| CARD9 | Orphanet:457088 | Predisposition to invasive fungal disease due to CARD9 deficiency |
| KCNT1 | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| KCNT1 | Orphanet:98784 | Sleep-related hypermotor epilepsy |
| ODAD1 | Orphanet:244 | Primary ciliary dyskinesia |
| ABCA2 | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
| NOTCH3 | Orphanet:136 | Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy |
| NOTCH3 | Orphanet:2591 | Infantile myofibromatosis |
| NOTCH3 | Orphanet:2789 | Lateral meningocele syndrome |
Cohort genes → proteins
9 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| NOTCH1 | HGNC:7881 | ENSG00000148400 | P46531 | Neurogenic locus notch homolog protein 1 | gencc,clinvar |
| CARD9 | HGNC:16391 | ENSG00000187796 | Q9H257 | Caspase recruitment domain-containing protein 9 | clinvar |
| KCNT1 | HGNC:18865 | ENSG00000107147 | Q5JUK3 | Potassium channel subfamily T member 1 | clinvar |
| ODAD1 | HGNC:26560 | ENSG00000105479 | Q96M63 | Outer dynein arm-docking complex subunit 1 | clinvar |
| C9orf163 | HGNC:26718 | ENSG00000196366 | Q8N9P6 | Uncharacterized protein C9orf163 | clinvar |
| ABCA2 | HGNC:32 | ENSG00000107331 | Q9BZC7 | ATP-binding cassette sub-family A member 2 | clinvar |
| MIR4673 | HGNC:41574 | ENSG00000263403 | microRNA 4673 | clinvar | |
| LINC01451 | HGNC:48599 | ENSG00000279141 | long intergenic non-protein coding RNA 1451 | clinvar | |
| NOTCH3 | HGNC:7883 | ENSG00000074181 | Q9UM47 | Neurogenic locus notch homolog protein 3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| NOTCH1 | Neurogenic locus notch homolog protein 1 | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. |
| CARD9 | Caspase recruitment domain-containing protein 9 | Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors. |
| KCNT1 | Potassium channel subfamily T member 1 | Sodium-activated K(+) channel. |
| ODAD1 | Outer dynein arm-docking complex subunit 1 | Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. |
| 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. |
| NOTCH3 | Neurogenic locus notch homolog protein 3 | Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. |
Protein-family classification
Druggable: 2 · Difficult: 2 · Unknown: 5 · Druggable fraction: 0.22
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 |
|---|---|---|---|
| Ion channel | 1 | 12.4× | 0.147 |
| Transporter | 1 | 8.6× | 0.147 |
| Scaffold/PPI | 2 | 3.8× | 0.147 |
| Other/Unknown | 5 | 1.0× | 0.641 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| NOTCH1 | Scaffold/PPI | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom | |
| CARD9 | Other/Unknown | no | CARD, DEATH-like_dom_sf, CARD_CARD9 | |
| KCNT1 | Ion channel | yes | RCK_N, K_chnl_BK_asu, K_chnl_dom | |
| ODAD1 | Other/Unknown | no | ODAD1_CC, ODA-DC/CCD | |
| C9orf163 | Other/Unknown | no | ||
| ABCA2 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM | |
| MIR4673 | Other/Unknown | no | ||
| LINC01451 | Other/Unknown | no | ||
| NOTCH3 | Scaffold/PPI | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom |
Expression context
Cohort genes with no expression data: 0.
7 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| colonic epithelium | 2 |
| right hemisphere of cerebellum | 2 |
| right uterine tube | 2 |
| ventricular zone | 1 |
| visceral pleura | 1 |
| leukocyte | 1 |
| monocyte | 1 |
| mononuclear cell | 1 |
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| bronchial epithelial cell | 1 |
| oviduct epithelium | 1 |
| myocardium | 1 |
| pituitary gland | 1 |
| C1 segment of cervical spinal cord | 1 |
| spinal cord | 1 |
| muscle of leg | 1 |
| skeletal muscle tissue | 1 |
| sural nerve | 1 |
| granulocyte | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| NOTCH1 | 272 | ubiquitous | marker | ventricular zone, colonic epithelium, visceral pleura |
| CARD9 | 172 | broad | marker | monocyte, mononuclear cell, leukocyte |
| KCNT1 | 153 | tissue_specific | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| ODAD1 | 174 | broad | marker | oviduct epithelium, right uterine tube, bronchial epithelial cell |
| C9orf163 | 121 | tissue_specific | yes | right uterine tube, myocardium, pituitary gland |
| ABCA2 | 234 | ubiquitous | marker | C1 segment of cervical spinal cord, spinal cord, right hemisphere of cerebellum |
| MIR4673 | 64 | yes | sural nerve, skeletal muscle tissue, muscle of leg | |
| LINC01451 | 117 | marker | colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, granulocyte | |
| NOTCH3 | 273 | ubiquitous | marker | popliteal artery, tibial artery, right coronary artery |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NOTCH1 | 7,411 |
| NOTCH3 | 4,403 |
| CARD9 | 3,636 |
| ABCA2 | 1,678 |
| KCNT1 | 1,562 |
| ODAD1 | 1,224 |
| C9orf163 | 54 |
| MIR4673 | 0 |
| LINC01451 | 0 |
Structural data
PDB: 5 · AlphaFold-only: 2 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| NOTCH1 | P46531 | 29 |
| CARD9 | Q9H257 | 8 |
| KCNT1 | Q5JUK3 | 6 |
| NOTCH3 | Q9UM47 | 6 |
| ODAD1 | Q96M63 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ABCA2 | Q9BZC7 | 71.46 |
| C9orf163 | Q8N9P6 | 33.64 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 9 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 |
|---|---|---|---|---|
| Defective LFNG causes SCDO3 | 2 | 1142.0× | 2e-05 | NOTCH1, NOTCH3 |
| Pre-NOTCH Processing in the Endoplasmic Reticulum | 2 | 951.7× | 2e-05 | NOTCH1, NOTCH3 |
| Pre-NOTCH Processing in Golgi | 2 | 317.2× | 2e-04 | NOTCH1, NOTCH3 |
| NOTCH3 Intracellular Domain Regulates Transcription | 2 | 219.6× | 2e-04 | NOTCH1, NOTCH3 |
| Notch-HLH transcription pathway | 2 | 203.9× | 2e-04 | NOTCH1, NOTCH3 |
| Pre-NOTCH Transcription and Translation | 2 | 61.4× | 0.002 | NOTCH1, NOTCH3 |
| Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling | 1 | 571.0× | 0.009 | NOTCH1 |
| Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 1 | 407.9× | 0.010 | NOTCH1 |
| Noncanonical activation of NOTCH3 | 1 | 356.9× | 0.010 | NOTCH3 |
| Regulation of NFE2L2 gene expression | 1 | 356.9× | 0.010 | NOTCH1 |
| NFE2L2 regulating tumorigenic genes | 1 | 237.9× | 0.013 | NOTCH1 |
| RUNX3 regulates NOTCH signaling | 1 | 203.9× | 0.014 | NOTCH1 |
| Constitutive Signaling by NOTCH1 HD Domain Mutants | 1 | 190.3× | 0.014 | NOTCH1 |
| Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells | 1 | 178.4× | 0.014 | NOTCH1 |
| ABC transporters in lipid homeostasis | 1 | 150.3× | 0.014 | ABCA2 |
| MECP2 regulates neuronal receptors and channels | 1 | 150.3× | 0.014 | NOTCH1 |
| NOTCH4 Intracellular Domain Regulates Transcription | 1 | 142.8× | 0.014 | NOTCH1 |
| NOTCH3 Activation and Transmission of Signal to the Nucleus | 1 | 119.0× | 0.016 | NOTCH3 |
| Formation of paraxial mesoderm | 1 | 102.0× | 0.017 | NOTCH1 |
| Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways | 1 | 89.2× | 0.018 | CARD9 |
| Activated NOTCH1 Transmits Signal to the Nucleus | 1 | 89.2× | 0.018 | NOTCH1 |
| Nuclear events stimulated by ALK signaling in cancer | 1 | 81.6× | 0.019 | NOTCH1 |
| NOD1/2 Signaling Pathway | 1 | 79.3× | 0.019 | CARD9 |
| NOTCH1 Intracellular Domain Regulates Transcription | 1 | 59.5× | 0.022 | NOTCH1 |
| C-type lectin receptors (CLRs) | 1 | 59.5× | 0.022 | CARD9 |
| Somitogenesis | 1 | 58.3× | 0.022 | NOTCH1 |
| Constitutive Signaling by NOTCH1 PEST Domain Mutants | 1 | 49.2× | 0.024 | NOTCH1 |
| Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 1 | 49.2× | 0.024 | NOTCH1 |
| Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells) | 1 | 36.6× | 0.031 | NOTCH1 |
| CLEC7A (Dectin-1) signaling | 1 | 35.7× | 0.031 | CARD9 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 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 muramyl dipeptide | 2 | 468.1× | 0.002 | NOTCH1, CARD9 |
| coronary sinus valve morphogenesis | 1 | 2808.7× | 0.006 | NOTCH1 |
| Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation | 1 | 2808.7× | 0.006 | NOTCH1 |
| foregut morphogenesis | 1 | 2808.7× | 0.006 | NOTCH1 |
| negative regulation of intracellular cholesterol transport | 1 | 2808.7× | 0.006 | ABCA2 |
| regulation of epithelial cell proliferation involved in prostate gland development | 1 | 2808.7× | 0.006 | NOTCH1 |
| venous endothelial cell differentiation | 1 | 2808.7× | 0.006 | NOTCH1 |
| negative regulation of phospholipid biosynthetic process | 1 | 2808.7× | 0.006 | ABCA2 |
| negative regulation of sphingolipid biosynthetic process | 1 | 2808.7× | 0.006 | ABCA2 |
| regulation of protein localization to cell periphery | 1 | 2808.7× | 0.006 | ABCA2 |
| endocardium morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| coronary vein morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| cardiac right atrium morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| growth involved in heart morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| obsolete negative regulation of cell proliferation involved in heart valve morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| cell differentiation in spinal cord | 1 | 1404.3× | 0.006 | NOTCH1 |
| regulation of interleukin-2 production | 1 | 1404.3× | 0.006 | CARD9 |
| negative regulation of steroid metabolic process | 1 | 1404.3× | 0.006 | ABCA2 |
| ceramide translocation | 1 | 1404.3× | 0.006 | ABCA2 |
| regulation of post-translational protein modification | 1 | 1404.3× | 0.006 | ABCA2 |
| positive regulation of aorta morphogenesis | 1 | 1404.3× | 0.006 | NOTCH1 |
| negative regulation of receptor-mediated endocytosis involved in cholesterol transport | 1 | 1404.3× | 0.006 | ABCA2 |
| mitral valve formation | 1 | 936.2× | 0.006 | NOTCH1 |
| cardiac chamber formation | 1 | 936.2× | 0.006 | NOTCH1 |
| auditory receptor cell fate commitment | 1 | 936.2× | 0.006 | NOTCH1 |
| positive regulation of low-density lipoprotein particle receptor catabolic process | 1 | 936.2× | 0.006 | ABCA2 |
| retinal cone cell differentiation | 1 | 936.2× | 0.006 | NOTCH1 |
| secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development | 1 | 936.2× | 0.006 | NOTCH1 |
| cardiac vascular smooth muscle cell development | 1 | 936.2× | 0.006 | NOTCH1 |
| vasculogenesis involved in coronary vascular morphogenesis | 1 | 936.2× | 0.006 | NOTCH1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 3 · Undrugged: 6
Druggability breadth: 3 of 9 evidence-associated genes (33%) 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 |
|---|---|
| KCNT1 | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| KCNT1 | 2 | 4 |
| NOTCH1 | 1 | 2 |
| NOTCH3 | 1 | 2 |
| CARD9 | 0 | 0 |
| ODAD1 | 0 | 0 |
| C9orf163 | 0 | 0 |
| ABCA2 | 0 | 0 |
| MIR4673 | 0 | 0 |
| LINC01451 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BEPRIDIL | 4 | KCNT1 |
| QUINIDINE | 4 | KCNT1 |
| VAREGACESTAT | 2 | NOTCH1, NOTCH3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| KCNT1 | 24 | Binding:24 |
| NOTCH1 | 23 | Binding:19, ADMET:4 |
| NOTCH3 | 3 | Binding:3 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
3 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) |
|---|---|---|
| BEPRIDIL | 4 | KCNT1 |
| QUINIDINE | 4 | KCNT1 |
| VAREGACESTAT | 2 | NOTCH1, NOTCH3 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | KCNT1 |
| B | Phased (≥1) drug, not yet approved | 2 | NOTCH1, NOTCH3 |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | ABCA2 |
| E | Difficult family or no structure, no drug | 5 | CARD9, ODAD1, C9orf163, MIR4673, LINC01451 |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CARD9 | 0 | — |
| ODAD1 | 0 | — |
| C9orf163 | 0 | — |
| ABCA2 | 0 | — |
| MIR4673 | 0 | — |
| LINC01451 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.