Brain ischemia

Summary

Brain ischemia (MONDO:0005299) is a disease with 2 cohort genes and 87 clinical trials. Top therapeutic interventions include aspirin, cilostazol, and probucol.

At a glance

• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 87

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain ischemia
Mondo ID	MONDO:0005299
MeSH	D002545
DOID	DOID:2316
NCIT	C78394
SNOMED CT	389100007
UMLS	C0917798
MedGen	182975
Anatomy (UBERON)	UBERON:0000955
Is cancer (heuristic)	no

Also known as: brain ischaemic disease · brain ischemia · brain ischemic disease · cerebrovascular ischemia · ischaemic disease of brain · ischemia cerebrovascular · ischemic disease of brain

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › ischemic disease › brain ischemia

Related subtypes (5): limb ischemia, retinal ischemia, ischemic bowel disorder, myocardial ischemia, peripheral ischemia

Subtypes (3): transient ischemic attack, brain hypoxia - ischemia, 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

3 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
268037	46;XY;t(2;14)(p22;q24.3)dn		Likely pathogenic	criteria provided, single submitter
183327	NM_001999.4(FBN2):c.1064G>A (p.Gly355Asp)	FBN2	Likely pathogenic	no assertion criteria provided
1342911	NM_001252102.2(KIF21B):c.433G>C (p.Ala145Pro)	KIF21B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBN2	Orphanet:115	Congenital contractural arachnodactyly

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KIF21B	HGNC:29442	ENSG00000116852	O75037	Kinesin-like protein KIF21B	clinvar
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF21B	Kinesin-like protein KIF21B	Plus-end directed microtubule-dependent motor protein which displays processive activity.
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF21B	Scaffold/PPI	no		WD40_rpt, Kinesin_motor_dom, WD40/YVTN_repeat-like_dom_sf
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 10	1
cortical plate	1
ganglionic eminence	1
adrenal tissue	1
cartilage tissue	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF21B	216	ubiquitous	marker	cortical plate, ganglionic eminence, Brodmann (1909) area 10
FBN2	194	ubiquitous	marker	cartilage tissue, placenta, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN2	2,570
KIF21B	1,201

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIF21B	O75037	70.07
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Elastic fibre formation	1	167.9×	0.030	FBN2
Molecules associated with elastic fibres	1	154.3×	0.030	FBN2
Kinesins	1	89.2×	0.030	KIF21B
Golgi-to-ER retrograde transport	1	66.4×	0.030	KIF21B
Degradation of the extracellular matrix	1	58.9×	0.030	FBN2
COPI-dependent Golgi-to-ER retrograde traffic	1	55.4×	0.030	KIF21B
Intra-Golgi and retrograde Golgi-to-ER traffic	1	52.4×	0.030	KIF21B
Factors involved in megakaryocyte development and platelet production	1	33.2×	0.041	KIF21B
Membrane Trafficking	1	18.5×	0.057	KIF21B
Hemostasis	1	18.0×	0.057	KIF21B
Vesicle-mediated transport	1	17.4×	0.057	KIF21B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete sequestering of TGFbeta in extracellular matrix	1	2106.5×	0.004	FBN2
bone trabecula formation	1	1053.2×	0.004	FBN2
embryonic eye morphogenesis	1	766.0×	0.004	FBN2
embryonic limb morphogenesis	1	200.6×	0.009	FBN2
positive regulation of bone mineralization	1	195.9×	0.009	FBN2
camera-type eye development	1	179.3×	0.009	FBN2
microtubule-based movement	1	147.8×	0.010	KIF21B
glucose metabolic process	1	127.7×	0.010	FBN2
positive regulation of osteoblast differentiation	1	112.3×	0.010	FBN2
glucose homeostasis	1	65.3×	0.015	FBN2

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Abciximab	Phase 3 (in late-stage trials)
Alteplase	Phase 3 (in late-stage trials)
Citicoline	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Nerinetide	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sulfur Hexafluoride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Autologous Cord Blood, Darbepoetin Alfa, Magnesium Sulfate Anhydrous, Tenecteplase, Topiramate, Xenon.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIF21B	0	0
FBN2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	2	KIF21B, FBN2

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)
KIF21B	0	—
FBN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 87.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	62
PHASE4	8
PHASE2	7
PHASE1	5
PHASE3	3
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00120588	PHASE4	COMPLETED	Neuroprotection by Magnesium Sulfate Given to Women at Risk of Very Preterm Birth
NCT00161070	PHASE4	COMPLETED	ESPRIT: European/Australasian Stroke Prevention in Reversible Ischaemia Trial
NCT01013532	PHASE4	UNKNOWN	PreventIon of CArdiovascular Events in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage
NCT01104311	PHASE4	TERMINATED	Strategy for Adequate Blood Pressure Lowering in the Patients With Intracranial Atherosclerosis
NCT02483169	PHASE4	UNKNOWN	PreventIon of IMT Progression in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage-IMT Study
NCT04386525	PHASE4	UNKNOWN	Omega 3 and Ischemic Stroke; Fish Oil as an Option
NCT05068349	PHASE4	UNKNOWN	For Patients With Ischemic Stroke, Clinically Study the Effectiveness and Safety of Butylphthalide.
NCT06081283	PHASE4	TERMINATED	Antiseizure Medication in Seizure Networks at Early Acute Brain Injury
NCT00073372	PHASE3	TERMINATED	A Study of Effectiveness and Safety of Abciximab in Patients With Acute Ischemic Stroke (AbESTT-II)
NCT00147316	PHASE3	COMPLETED	Japan Alteplase Clinical Trial (J-ACT): Efficacy and Safety Study of Tissue Plasminogen Activator (Alteplase) for Ischemic Stroke
NCT01407614	PHASE2/PHASE3	TERMINATED	The Tilburg Vasospasm Study
NCT05131295	PHASE3	COMPLETED	Dapsone Use in Patients With Aneurysmal Subarachnoid Hemorrhage.
NCT00190047	PHASE2	COMPLETED	Effects Of DP-b99 On Neurological Function In Subjects With Acute Ischemic Hemispheric Stroke
NCT00987922	PHASE2	COMPLETED	Mild Hypothermia in Acute Ischemic Stroke
NCT01059149	PHASE2	TERMINATED	Safety and Long-term Effectiveness of High Frequency Repetitive Transcranial Magnetic Stimulation of Stroke (RAICup)
NCT01845441	PHASE2	TERMINATED	Use of Dexmedetomidine in Acute Stroke and Cerebral Vasospasm Interventions
NCT02101606	PHASE2	COMPLETED	Penumbral Based Novel Thrombolytic Therapy in Acute Ischemic Stroke
NCT02957123	PHASE1/PHASE2	COMPLETED	Intranasal Inhalations of Bioactive Factors Produced by M2 Macrophages in Patients With Organic Brain Syndrome
NCT03448159	PHASE2	COMPLETED	Fluoxetine Opens Window to Improve Motor Recovery After Stroke
NCT03684564	PHASE2	COMPLETED	RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome
NCT01438593	PHASE1	UNKNOWN	Study of Purified Umbilical Cord Blood CD34+ Stem Cell on Chronic Ischemic Stroke
NCT01556802	PHASE1	UNKNOWN	Use of Minocicline in Patients With Stroke
NCT01673932	PHASE1	UNKNOWN	Safety and Feasibility Study of Umbilical Cord Blood Mononuclear Cells Transplant to Treat Ischemic Stroke
NCT01749358	PHASE1	COMPLETED	Dose Optimization for Stroke Evaluation
NCT02618031	PHASE1	COMPLETED	The Capillary Index Score Trial
NCT02900521	Not specified	RECRUITING	Population-based Brest Stroke Registry
NCT03592563	Not specified	RECRUITING	CUHK Brain Health Longitudinal Study
NCT03962127	Not specified	ACTIVE_NOT_RECRUITING	MIDNOR-STROKE- a Long Term Follow-up Study of Patients With First Ever Ischemic Stroke in Central Norway
NCT04421326	Not specified	RECRUITING	Multimodal Investigation of Intracranial Clot Environment
NCT04981184	Not specified	RECRUITING	Informative of Surface Electromyography and Prognostic Factors in Assessing the Recovery of Balance and Gait After Stroke
NCT04992195	Not specified	RECRUITING	Impact of COVID-19 Vaccines on Cerebrovascular Health
NCT05845983	Not specified	NOT_YET_RECRUITING	LA Improves the Prognosis of Patients With ICVD
NCT06121336	Not specified	RECRUITING	PRecisiOn Medicine In StrokE: Evolution of Plasma Brain-Derived Tau in Acute Stroke
NCT06216457	Not specified	NOT_YET_RECRUITING	Study on the Performance of a Machine Learning Algorithm Recognizing and Triaging Large Vessel Occlusions Using Non-contrast CT Scans
NCT06270927	Not specified	ACTIVE_NOT_RECRUITING	A Feasibility Study for Randomization of Code Stroke Imaging Strategies
NCT06409806	Not specified	RECRUITING	Electrocorticographic Monitoring of Brain Retraction Injury (EMBRI)
NCT06873477	Not specified	RECRUITING	Evaluation of Patients Affected by Traumatic and Hypoxic-ischemic Brain Injury
NCT06954610	Not specified	RECRUITING	Cardiac Assessment for Recurrent Stroke Risk Evaluation in Atrial Fibrillation
NCT07069452	Not specified	RECRUITING	Prognostic Value of Isolated and Combined Score Aspects in Acute Ischemic Stroke
NCT07181564	Not specified	RECRUITING	Anesthesia Techniques, Neuroprotection and Surgical Field in FESS Under Controlled Hypotension

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	2
CILOSTAZOL	4	2
PROBUCOL	4	2
ABCIXIMAB	4	1
ALTEPLASE	4	1
DAPSONE	4	1
DEFEROXAMINE	4	1
DIPYRIDAMOLE	4	1
ETOMIDATE	4	1
FOSPHENYTOIN	4	1
LEVETIRACETAM	4	1
PHENOBARBITAL	4	1
TRANYLCYPROMINE	4	1
VALPROATE SODIUM	4	1
MAGNESIUM	3	2
RAC-3-N-BUTYLPHTHALIDE	3	2
LACTOBACILLUS ACIDOPHILUS	3	1
ALGELDRATE	2	1
ETIRACETAM	2	1
LUFENURON	2	1
CHEMBL5282669	0	2
CHEMBL249818	0	2
CHEMBL4635234	0	1
LEVITIRACETAM	0	1
S-ETOMIDATE	-1	1