Ischemic stroke

Summary

Ischemic stroke (MONDO:1060198) is a disease (an umbrella term covering 5 Mondo subtypes) with 11 cohort genes and 1,598 clinical trials. Top therapeutic interventions include tenecteplase, alteplase, and cilostazol.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 11
• ClinVar variants: 54
• Clinical trials: 1,598

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ischemic stroke
Mondo ID	MONDO:1060198
DOID	DOID:0051062
UMLS	C0948008
MedGen	215292
Is cancer (heuristic)	no

Also known as: ischaemic stroke

Data availability: 54 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › stroke disorder › ischemic stroke

Related subtypes (3): large artery stroke, spinal cord ischemia, hemorrhagic stroke

Subtypes (5): cerebral infarction, transient ischemic attack, brain stem infarction, intracranial embolism, pediatric arterial ischemic stroke

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

54 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 11 conflicting classifications of pathogenicity, 7 likely pathogenic, 6 pathogenic, 4 benign, 4 pathogenic/likely pathogenic, 4 benign/likely benign, 2 likely benign, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic/likely pathogenic/pathogenic, low penetrance/established risk allele; risk factor, 1 drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
548953	GRCh37/hg19 Xq23(chrX:108919564-108929311)	ACSL4	Pathogenic	criteria provided, single submitter
13310	NM_000506.5(F2):c.*97G>A	F2	Pathogenic/Likely pathogenic/Pathogenic, low penetrance/Established risk allele; risk factor	criteria provided, multiple submitters, no conflicts
2706763	NM_000506.5(F2):c.1499G>A (p.Arg500Gln)	F2	Pathogenic	criteria provided, multiple submitters, no conflicts
2734021	NM_000130.5(F5):c.3088C>T (p.Arg1030Ter)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
2866617	NM_000130.5(F5):c.5453del (p.Leu1818fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2895285	NM_000130.5(F5):c.2021del (p.Lys674fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430053	NM_000130.5(F5):c.5037dup (p.Ser1680fs)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
627264	NM_000130.5(F5):c.1830_1831dup (p.His611fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42394	NM_000138.5(FBN1):c.5788+5G>A	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208501	NM_000435.3(NOTCH3):c.457C>T (p.Arg153Cys)	NOTCH3	Pathogenic	criteria provided, multiple submitters, no conflicts
812745	NM_000435.3(NOTCH3):c.634T>C (p.Cys212Arg)	NOTCH3	Pathogenic	no assertion criteria provided
3599612	NM_000506.5(F2):c.317-1G>A	F2	Likely pathogenic	criteria provided, single submitter
2887062	NM_000130.5(F5):c.4962_4971+3del	F5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3600169	NM_000130.5(F5):c.5816T>G (p.Leu1939Ter)	F5	Likely pathogenic	criteria provided, single submitter
3600193	NM_000130.5(F5):c.2846del (p.Leu949fs)	F5	Likely pathogenic	criteria provided, single submitter
3600196	NM_000130.5(F5):c.2079T>G (p.Tyr693Ter)	F5	Likely pathogenic	criteria provided, single submitter
3600213	NM_000130.5(F5):c.1297-1G>C	F5	Likely pathogenic	criteria provided, single submitter
3600215	NM_000130.5(F5):c.1059del (p.Phe353fs)	F5	Likely pathogenic	criteria provided, single submitter
642	NM_000130.4(F5):c.1601G>A (p.Arg534Gln)	F5	drug response	reviewed by expert panel
13302	NM_000506.3(F2):c.598G>A (p.Glu200Lys)	F2	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
2697011	NM_000506.5(F2):c.1542C>A (p.Asn514Lys)	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2868567	NM_000506.5(F2):c.316+16G>A	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
627262	NM_000506.5(F2):c.1814_1815del (p.His605fs)	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1771009	NM_000130.5(F5):c.136C>G (p.Arg46Gly)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293607	NM_000130.5(F5):c.3442T>C (p.Ser1148Pro)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579171	NM_000130.5(F5):c.5265A>G (p.Ile1755Met)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
627181	NM_000130.5(F5):c.5408A>G (p.His1803Arg)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
716054	NM_000130.5(F5):c.3162A>C (p.Glu1054Asp)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
787578	NM_000130.5(F5):c.4589A>C (p.Glu1530Ala)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870845	NM_000130.5(F5):c.3221A>G (p.Asn1074Ser)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 33 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F2	Orphanet:325	Congenital factor II deficiency
F2	Orphanet:329217	Cerebral sinovenous thrombosis
F5	Orphanet:131	Budd-Chiari syndrome
F5	Orphanet:326	Congenital factor V deficiency
F5	Orphanet:329217	Cerebral sinovenous thrombosis
F5	Orphanet:391320	East Texas bleeding disorder
F5	Orphanet:599579	Factor V Amsterdam bleeding disorder
F5	Orphanet:600194	Factor V Atlanta bleeding disorder
ACSL4	Orphanet:777	X-linked non-syndromic intellectual disability
ACSL4	Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
GRN	Orphanet:100069	Semantic dementia
GRN	Orphanet:100070	Progressive non-fluent aphasia
GRN	Orphanet:275864	Behavioral variant of frontotemporal dementia
GRN	Orphanet:314629	CLN11 disease
MT-CO2	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO2	Orphanet:550	MELAS
MT-CYB	Orphanet:104	Leber hereditary optic neuropathy
MT-CYB	Orphanet:137675	Histiocytoid cardiomyopathy
MT-CYB	Orphanet:1460	Isolated complex III deficiency
NOTCH3	Orphanet:136	Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy
NOTCH3	Orphanet:2591	Infantile myofibromatosis
NOTCH3	Orphanet:2789	Lateral meningocele syndrome

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NANOS3	HGNC:22048	ENSG00000187556	P60323	Nanos homolog 3	clinvar
F2	HGNC:3535	ENSG00000180210	P00734	Prothrombin	clinvar
F5	HGNC:3542	ENSG00000198734	P12259	Coagulation factor V	clinvar
ACSL4	HGNC:3571	ENSG00000068366	O60488	Long-chain-fatty-acid–CoA ligase 4	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
GRN	HGNC:4601	ENSG00000030582	P28799	Progranulin	clinvar
MT-CO2	HGNC:7421	ENSG00000198712	P00403	Cytochrome c oxidase subunit 2	clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar
NOS3	HGNC:7876	ENSG00000164867	P29474	Nitric oxide synthase 3	clinvar
NOTCH3	HGNC:7883	ENSG00000074181	Q9UM47	Neurogenic locus notch homolog protein 3	clinvar
PRKCH	HGNC:9403	ENSG00000027075	C0HM02	PRKCH upstream open reading frame 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NANOS3	Nanos homolog 3	Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase.
F2	Prothrombin	Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C.
F5	Coagulation factor V	Central regulator of hemostasis.
ACSL4	Long-chain-fatty-acid–CoA ligase 4	Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
GRN	Progranulin	Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation.
MT-CO2	Cytochrome c oxidase subunit 2	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CYB	Cytochrome b	Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.
NOS3	Nitric oxide synthase 3	Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.
NOTCH3	Neurogenic locus notch homolog protein 3	Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination.
PRKCH	PRKCH upstream open reading frame 2	Product of an upstream open reading frame (ORF) of PRKCH which regulates translation of the downstream protein kinase C eta (PKC-eta) ORF.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 5 · Druggable fraction: 0.36

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
Protease	1	3.3×	0.665
Kinase	1	2.5×	0.665
Enzyme (other)	2	2.2×	0.665
Scaffold/PPI	1	1.6×	0.721
Other/Unknown	5	0.8×	0.840
Transcription factor	1	0.8×	0.840

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NANOS3	Transcription factor	no		Nanos/Xcar2, Znf_nanos-typ, Nanos_sf
F2	Protease	yes	3.4.21.5	Kringle, GLA_domain, Trypsin_dom
F5	Other/Unknown	no		FA58C, Cupredoxin, Galactose-bd-like_sf
ACSL4	Enzyme (other)	yes	6.2.1.15	AMP-dep_synth/lig_dom, AMP-binding_CS, ANL_N_sf
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
GRN	Other/Unknown	no		Granulin, Granulin_sf, Granulin_fam
MT-CO2	Other/Unknown	no		Copper_CuA, CcO_II-like_C, Cupredoxin
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM
NOS3	Enzyme (other)	yes	1.14.13.39	Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase
NOTCH3	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
PRKCH	Kinase	yes	2.7.11.13	PRKCH_uORF2, C2_dom, Prot_kinase_dom

Expression context

Cohort genes with no expression data: 0.

10 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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
liver	2
right lobe of liver	2
monocyte	2
apex of heart	2
amygdala	1
prefrontal cortex	1
primordial germ cell in gonad	1
male germ line stem cell (sensu Vertebrata) in testis	1
choroid plexus epithelium	1
adrenal tissue	1
mononuclear cell	1
decidua	1
skin of hip	1
synovial joint	1
stromal cell of endometrium	1
rectum	1
transverse colon	1
pituitary gland	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NANOS3	129	broad	yes	primordial germ cell in gonad, prefrontal cortex, amygdala
F2	117	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
F5	206	broad	marker	right lobe of liver, liver, choroid plexus epithelium
ACSL4	268	ubiquitous	marker	adrenal tissue, monocyte, mononuclear cell
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
GRN	301	ubiquitous	marker	monocyte, granulocyte, stromal cell of endometrium
MT-CO2	134	ubiquitous	marker	granulocyte, rectum, transverse colon
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin
NOS3	168	broad	marker	spleen, apex of heart, lower esophagus mucosa
NOTCH3	273	ubiquitous	marker	popliteal artery, tibial artery, right coronary artery
PRKCH	274	ubiquitous	marker	parotid gland, granulocyte, esophagus squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH3	4,403
FBN1	3,640
NOS3	3,606
MT-CYB	3,317
MT-CO2	3,057
ACSL4	3,040
F2	2,709
F5	1,754
GRN	1,490
NANOS3	932

Intra-cohort edges

A	B	Sources
F2	F5	biogrid_interaction, string_interaction
MT-CO2	MT-CYB	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F2	P00734	475
NOS3	P29474	105
F5	P12259	18
FBN1	P35555	11
GRN	P28799	8
NOTCH3	Q9UM47	6
MT-CYB	P00156	5
MT-CO2	P00403	4
PRKCH	C0HM02	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACSL4	O60488	90.46
NANOS3	P60323	71.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 87. Enrichment computed across 11 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Amplification and propagation of coagulation cascade	2	115.3×	0.007	F2, F5
Initiation of coagulation cascade	2	86.5×	0.007	F2, F5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	3	23.6×	0.007	F2, F5, FBN1
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	1	1038.2×	0.014	F2
Defective factor VIII causes hemophilia A	1	1038.2×	0.014	F2
Regulation of clotting cascade	2	42.4×	0.014	F2, F5
NOSIP mediated eNOS trafficking	1	519.1×	0.019	NOS3
Free fatty acids regulate insulin secretion	1	346.1×	0.019	ACSL4
Intracellular metabolism of fatty acids regulates insulin secretion	1	346.1×	0.019	ACSL4
R-HSA-9651496	1	346.1×	0.019	F2
Defective F8 cleavage by thrombin	1	346.1×	0.019	F2
Defective cleavage of FV variant at a.a.534	1	346.1×	0.019	F5
Defective cleavage of FV variant at R334	1	346.1×	0.019	F5
R-HSA-140875	1	259.6×	0.021	F2
Defective factor XII causes hereditary angioedema	1	259.6×	0.021	F2
Diseases of hemostasis	1	259.6×	0.021	F2
NOSTRIN mediated eNOS trafficking	1	207.6×	0.021	NOS3
Defective LFNG causes SCDO3	1	207.6×	0.021	NOTCH3
Mitochondrial translation termination	2	20.0×	0.021	MT-CO2, MT-CYB
Platelet activation, signaling and aggregation	2	19.2×	0.021	F2, PRKCH
Post-translational protein phosphorylation	2	18.2×	0.021	F5, FBN1
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	173.0×	0.022	NOTCH3
Respiratory electron transport	2	17.3×	0.022	MT-CO2, MT-CYB
R-HSA-140837	1	129.8×	0.027	F2
Noncanonical activation of NOTCH3	1	129.8×	0.027	NOTCH3
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	115.3×	0.029	F2
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	103.8×	0.029	NOS3
Gamma-carboxylation of protein precursors	1	103.8×	0.029	F2
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	103.8×	0.029	F2
R-HSA-140877	1	86.5×	0.033	F2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 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 platelet activation	2	340.4×	0.003	F2, NOS3
negative regulation of prostaglandin secretion	1	1532.0×	0.017	ACSL4
ATP synthesis coupled electron transport	1	1532.0×	0.017	MT-CO2
response to D-galactosamine	1	1532.0×	0.017	MT-CYB
positive regulation of aspartic-type peptidase activity	1	1532.0×	0.017	GRN
regulation of the force of heart contraction by chemical signal	1	766.0×	0.017	NOS3
negative regulation of muscle hyperplasia	1	766.0×	0.017	NOS3
smooth muscle hyperplasia	1	766.0×	0.017	NOS3
positive regulation of translation in response to stress	1	766.0×	0.017	PRKCH
response to cobalamin	1	766.0×	0.017	MT-CYB
tetrahydrobiopterin metabolic process	1	766.0×	0.017	NOS3
positive regulation of inflammatory response to wounding	1	766.0×	0.017	GRN
positive regulation of trophectodermal cell proliferation	1	766.0×	0.017	GRN
regulation of nervous system process	1	510.7×	0.017	NOS3
response to vitamin K	1	510.7×	0.017	F5
post-embryonic eye morphogenesis	1	510.7×	0.017	FBN1
glomerular capillary formation	1	510.7×	0.017	NOTCH3
positive regulation of protein folding	1	510.7×	0.017	GRN
cellular respiration	2	78.6×	0.017	MT-CO2, MT-CYB
positive regulation of insulin secretion	2	46.4×	0.017	F2, ACSL4
negative regulation of translation	2	35.6×	0.017	NANOS3, PRKCH
positive regulation of cell growth	2	33.3×	0.017	F2, ACSL4
blood coagulation	2	31.6×	0.017	F2, F5
astrocyte activation involved in immune response	1	383.0×	0.018	GRN
electron transport coupled proton transport	1	383.0×	0.018	MT-CYB
obsolete sequestering of BMP in extracellular matrix	1	383.0×	0.018	FBN1
obsolete sequestering of TGFbeta in extracellular matrix	1	383.0×	0.018	FBN1
positive regulation of lysosome organization	1	383.0×	0.018	GRN
response to ethanol	2	26.6×	0.018	MT-CO2, MT-CYB
trophectodermal cell proliferation	1	306.4×	0.018	GRN

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 6

Druggability breadth: 8 of 11 evidence-associated genes (73%) 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
F2	INDIGOTINDISULFONATE
F5	EDOXABAN
MT-CO2	CELECOXIB
NOS3	CHLORZOXAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F2	48	4
MT-CO2	6	4
NOS3	6	4
F5	2	4
NOTCH3	1	2
NANOS3	0	0
ACSL4	0	0
FBN1	0	0
GRN	0	0
MT-CYB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDIGOTINDISULFONATE	4	F2
ARGATROBAN	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
EDOXABAN	4	F2, F5
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
RIVAROXABAN	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
APIXABAN	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
BETRIXABAN	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
DABIGATRAN ETEXILATE	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
CELECOXIB	4	MT-CO2
ROFECOXIB	4	MT-CO2
DICLOFENAC	4	MT-CO2
INDOMETHACIN	4	MT-CO2
VALDECOXIB	4	MT-CO2
CHLORZOXAZONE	4	NOS3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
F2	1,269	Binding:1216, Functional:38, ADMET:13, Toxicity:2
NOS3	188	Binding:178, ADMET:6, Functional:4
MT-CO2	47	Binding:41, ADMET:5, Toxicity:1
F5	10	Binding:10
NOTCH3	3	Binding:3
ACSL4	2	Binding:2
GRN	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F2	3.4.21.5	thrombin
ACSL4	6.2.1.15, 6.2.1.3	arachidonate-CoA ligase, long-chain-fatty-acid-CoA ligase
NOS3	1.14.13.39	nitric-oxide synthase (NADPH)
PRKCH	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
F2	1,269
NOS3	188

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

26 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)
INDIGOTINDISULFONATE	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
BETRIXABAN	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
DABIGATRAN ETEXILATE	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
CELECOXIB	4	MT-CO2
ROFECOXIB	4	MT-CO2
DICLOFENAC	4	MT-CO2
INDOMETHACIN	4	MT-CO2
VALDECOXIB	4	MT-CO2
CHLORZOXAZONE	4	NOS3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	F2, F5, MT-CO2, NOS3
B	Phased (≥1) drug, not yet approved	1	NOTCH3
C	Druggable family + PDB, no drug	1	PRKCH
D	Druggable family + AlphaFold only, no drug	1	ACSL4
E	Difficult family or no structure, no drug	4	NANOS3, FBN1, GRN, MT-CYB

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)
NANOS3	0	—
ACSL4	2	—
FBN1	0	—
GRN	2	—
MT-CYB	0	—
PRKCH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,598.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	525
PHASE2	171
PHASE3	165
PHASE4	90
PHASE1	62
PHASE1/PHASE2	40
PHASE2/PHASE3	37
EARLY_PHASE1	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04916197	PHASE4	RECRUITING	Effect of Postoperative Prolonged Sedation With Dexmedetomidine After Successful Reperfusion With EVT on Long-term Prognosis in Patients With AIS (PPDET)
NCT05589454	PHASE4	NOT_YET_RECRUITING	Intracranial Hemorrhage Risk of Intensive Statin in Acute Ischemic Stroke With Cerebral Microbleeds
NCT05910125	PHASE4	NOT_YET_RECRUITING	Aspirin Combined With Clopidogrel Versus Intravenous Alteplase for Acute Minor Stroke
NCT05912686	PHASE4	NOT_YET_RECRUITING	High-Dose Atorvastatin for Vascular Wall Protection in Thrombectomy Patients
NCT05995600	PHASE4	RECRUITING	Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE
NCT06139692	PHASE4	RECRUITING	Comparison of Perioperative Conscious Sedation During Endovascular Thrombectomy in Acute Ischemic Stroke
NCT06212674	PHASE4	RECRUITING	Single-stage Pulmonary Vein Isolation Combined With Percutaneous Left Atrial Appendage Occluder Implantation in Patients With Recent Onset Ischemic Stroke and Atrial Fibrillation
NCT06243133	PHASE4	NOT_YET_RECRUITING	Pair Antiplatelet THerapy in Ischemic Stroke With Intracranial Artery Stenosis
NCT06269432	PHASE4	RECRUITING	Precise Antiplatelet THerapy Guided by Platelet Aggregation Function in Ischemic STROKE（PATH-STROKE）
NCT06308952	PHASE4	RECRUITING	Atorvastatin Pretreatment in Cerebrovascular Events (APICES) After Flow Diverter Implantation
NCT06396858	PHASE4	NOT_YET_RECRUITING	Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke
NCT06486792	PHASE4	NOT_YET_RECRUITING	Stroke Prevention In Ischemic Stroke With Covert Atrial Fibrillation
NCT06498323	PHASE4	RECRUITING	Intravenous TNK vs TPA for AIS Treatment on MSU,a Prospective Multicenter RCT
NCT06571149	PHASE4	RECRUITING	Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake
NCT06645522	PHASE4	NOT_YET_RECRUITING	Safety and Efficacy of Edaravone Dexborneol for Acute Ischemic Stroke
NCT06653946	PHASE4	RECRUITING	the Predictors of Hemorrhagic Transformation Subtypes in Acute Embolic Stroke Patients
NCT06737549	PHASE4	RECRUITING	Effect of Specific Mode Electroacupuncture Stimulation Combined with NGF on Dysphagia After Ischaemic Stroke: a Pilot Randomized Controlled Trial
NCT06785727	PHASE4	NOT_YET_RECRUITING	StAtins in Frail OldEr Patients with Ischemic Stroke or Transient Ischemic Attack - the Randomized Controlled Trial
NCT07111559	PHASE4	RECRUITING	Lacunar Stroke hyperAcute Clinical Utilization of Novel Approach Regimens: Rt-PA vs. DAPT Randomised Clinical Trial
NCT07119021	PHASE4	RECRUITING	Efficacy and Safety Study of Ultra-early Mobile Stroke Unit Neuroprotection Combined With Revascularization for Acute Ischemic Stroke (EXCELLENT)
NCT07203625	PHASE4	RECRUITING	Tenecteplase Before Interhospital Transfer in Acute Basilar Artery Occlusion at 4.5 to 24 Hours
NCT07290751	PHASE4	RECRUITING	Intravenous Thrombolysis Combined With Tirofiban in Acute Ischemic Stroke
NCT07436156	PHASE4	RECRUITING	SUMMIT RISE Study of Acute Ischemic Stroke Patients
NCT07519044	PHASE4	RECRUITING	Safety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion
NCT07528456	PHASE4	NOT_YET_RECRUITING	Butylphthalide for Brain Edema After Endovascular Treatment
NCT07575984	PHASE4	RECRUITING	Mexidol® Safety and Efficacy in Treatment of Hyperacute and Acute Ischemic Stroke
NCT07609654	PHASE4	NOT_YET_RECRUITING	Oral Anticoagulation After Stroke With Prior ICH in Subjects With AF
NCT00077805	PHASE4	COMPLETED	PREVAIL: PREvention of VTE After Acute Ischemic Stroke With LMWH Enoxaparin ( - VTE: Venous Thromboembolism - LMWH: Low Molecular Weight Heparin)
NCT00328640	PHASE4	COMPLETED	Quality Improvement in Stroke Prevention (QUISP)
NCT00697151	PHASE4	COMPLETED	Patent Foramen Ovale in Cryptogenic Stroke Study
NCT00747279	PHASE4	UNKNOWN	Comparison of Two Strategies for Glycemic Control in Acute Ischemic Stroke
NCT00754429	PHASE4	COMPLETED	The Effect of Losartan Versus Amlodipine-based Therapy in Ischemic Stroke (0954-338)(COMPLETED)
NCT00868283	PHASE4	COMPLETED	The Safety and Efficacy of Cerebrolysin in Patients With Acute Ischemic Stroke
NCT00874601	PHASE4	UNKNOWN	Valsartan Efficacy on Modest Blood Pressure Reduction in Acute Ischemic Stroke
NCT00931788	PHASE4	COMPLETED	Preventing Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack
NCT00966316	PHASE4	COMPLETED	Establishment and Evaluation to the Effects of a Clinical Pathway for Acute Ischemic Stroke
NCT01088672	PHASE4	COMPLETED	Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO)
NCT01097967	PHASE4	UNKNOWN	Sleep Disordered Breathing in Transient Ischemic Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy
NCT01109836	PHASE4	COMPLETED	Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke
NCT01188824	PHASE4	COMPLETED	The Safety and Efficacy of Cilostazol in Ischemic Stroke Patients With Peripheral Arterial Disease (SPAD Study)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TENECTEPLASE	4	29
ALTEPLASE	4	25
CILOSTAZOL	4	15
TIROFIBAN	4	12
EDARAVONE	4	7
EPTIFIBATIDE	4	5
ALBUMIN HUMAN	4	4
EDOXABAN	4	4
SEMAGLUTIDE	4	4
VERAPAMIL	4	4
COLCHICINE	4	3
DIMETHYL FUMARATE	4	3
DORNASE ALFA	4	3
MINOCYCLINE	4	3
OXYGEN	4	3
PHENYLEPHRINE	4	3
APIXABAN	4	2
ARGATROBAN	4	2
ASPIRIN	4	2
ENOXAPARIN SODIUM	4	2
GLYBURIDE	4	2
LABETALOL	4	2
LOSARTAN	4	2
NATALIZUMAB	4	2
PRAVASTATIN	4	2
RIVAROXABAN	4	2
UROKINASE	4	2
WARFARIN	4	2
AGOMELATINE	4	1
ALIROCUMAB	4	1