Brain edema

Summary

Brain edema (MONDO:0006684) is a disease with 1 cohort gene and 29 clinical trials. Top therapeutic interventions include hydroxyethyl starch 130/0.4, mannitol, and sodium chloride.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain edema
Mondo ID	MONDO:0006684
EFO	EFO:1000845
MeSH	D001929
DOID	DOID:4724
SNOMED CT	2032001
UMLS	C0006114
MedGen	2337
MedDRA	10006121
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › brain edema

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
157684	NM_000352.6(ABCC8):c.1686C>T (p.His562=)	ABCC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC8	Orphanet:276575	Autosomal dominant hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:276598	Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:552	MODY
ABCC8	Orphanet:79134	DEND syndrome
ABCC8	Orphanet:79643	Autosomal recessive hyperinsulinism due to SUR1 deficiency
ABCC8	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
ABCC8	Orphanet:99886	Transient neonatal diabetes mellitus

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
ABCC8	HGNC:59	ENSG00000006071	Q09428	ATP-binding cassette sub-family C member 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCC8	ATP-binding cassette sub-family C member 8	Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCC8	Transporter	yes		ABCC8/9, ABCC8, ABC_transporter-like_ATP-bd

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
cerebellar hemisphere	1
islet of Langerhans	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC8	185	broad	marker	islet of Langerhans, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC8	2,826

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC8	Q09428	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Defective ABCC8 can cause hypo- and hyper-glycemias	1	5710.0×	0.002	ABCC8
ATP sensitive Potassium channels	1	2855.0×	0.002	ABCC8
Inwardly rectifying K+ channels	1	713.8×	0.005	ABCC8
ABC transporter disorders	1	439.2×	0.006	ABCC8
Regulation of insulin secretion	1	219.6×	0.010	ABCC8
Integration of energy metabolism	1	175.7×	0.010	ABCC8
Disorders of transmembrane transporters	1	139.3×	0.010	ABCC8
Potassium Channels	1	134.3×	0.010	ABCC8
Neuronal System	1	44.3×	0.028	ABCC8
Disease	1	13.1×	0.084	ABCC8
Metabolism	1	11.6×	0.086	ABCC8

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
negative regulation of neuroblast migration	1	16852.0×	9e-04	ABCC8
positive regulation of uterine smooth muscle relaxation	1	16852.0×	9e-04	ABCC8
glutamate secretion, neurotransmission	1	5617.3×	0.001	ABCC8
negative regulation of blood-brain barrier permeability	1	5617.3×	0.001	ABCC8
positive regulation of tight junction disassembly	1	3370.4×	0.002	ABCC8
response to pH	1	2808.7×	0.002	ABCC8
positive regulation of potassium ion transport	1	2106.5×	0.002	ABCC8
negative regulation of glial cell proliferation	1	1685.2×	0.002	ABCC8
negative regulation of low-density lipoprotein particle clearance	1	1532.0×	0.002	ABCC8
obsolete inorganic cation transmembrane transport	1	936.2×	0.003	ABCC8
response to zinc ion	1	624.1×	0.004	ABCC8
intracellular glucose homeostasis	1	581.1×	0.004	ABCC8
neuromuscular process	1	526.6×	0.004	ABCC8
negative regulation of insulin secretion	1	495.6×	0.004	ABCC8
cellular response to nutrient levels	1	468.1×	0.004	ABCC8
regulation of insulin secretion	1	391.9×	0.004	ABCC8
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.004	ABCC8
potassium ion import across plasma membrane	1	366.4×	0.004	ABCC8
action potential	1	358.6×	0.004	ABCC8
visual learning	1	306.4×	0.005	ABCC8
response to insulin	1	230.8×	0.006	ABCC8
female pregnancy	1	210.7×	0.006	ABCC8
potassium ion transport	1	191.5×	0.007	ABCC8
memory	1	183.2×	0.007	ABCC8
negative regulation of angiogenesis	1	168.5×	0.007	ABCC8
transmembrane transport	1	168.5×	0.007	ABCC8
positive regulation of tumor necrosis factor production	1	153.2×	0.007	ABCC8
potassium ion transmembrane transport	1	135.9×	0.008	ABCC8
response to lipopolysaccharide	1	124.8×	0.008	ABCC8
response to xenobiotic stimulus	1	69.1×	0.014	ABCC8

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Mannitol	Approved (phase 4)

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
ABCC8	REPAGLINIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC8	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
REPAGLINIDE	4	ABCC8
DIAZOXIDE	4	ABCC8
GLYBURIDE	4	ABCC8
CROMAKALIM	2	ABCC8
CLAMIKALANT	2	ABCC8
TIFENAZOXIDE	2	ABCC8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCC8	84	Functional:52, Binding:32

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)
REPAGLINIDE	4	ABCC8
DIAZOXIDE	4	ABCC8
GLYBURIDE	4	ABCC8
CROMAKALIM	2	ABCC8
CLAMIKALANT	2	ABCC8
TIFENAZOXIDE	2	ABCC8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC8
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: 29.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	22
PHASE3	4
PHASE4	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02037815	PHASE4	COMPLETED	Correlation of Measured and Calculated Serum Osmolality During Hyperosmolar Drugs Infusion in Patients After Craniotomy
NCT03573999	PHASE4	COMPLETED	Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation
NCT00088166	PHASE3	COMPLETED	XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors
NCT00226655	PHASE3	COMPLETED	An Open-Labeled, Extended-Use of XERECEPT (hCRF) for Patients in Studies NTI 0302, 0303, or Other Designated Studies
NCT00226668	PHASE3	WITHDRAWN	XERECEPT® (hCRF) for Primary Glioma Patients Requiring Dexamethasone to Treat Peritumoral Brain Edema
NCT02864953	PHASE3	TERMINATED	Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous BIIB093 (Glibenclamide) for Severe Cerebral Edema Following Large Hemispheric Infarction
NCT01369121	PHASE1/PHASE2	TERMINATED	Tolerability Study of Xerecept® in Pediatric Patients
NCT04057690	Not specified	ACTIVE_NOT_RECRUITING	Automatic PredICtion of Edema After Stroke
NCT04114799	Not specified	RECRUITING	Haemodynamical Optimization During Brain Surgery
NCT05622461	Not specified	RECRUITING	Setting Families on a Positive Path to Recovery After Pediatric TBI: Road-to-Recovery
NCT06451887	Not specified	RECRUITING	Early Identification of Malignant Brain Edema in laRge Artery oCclusive Stroke After Endovascular Therapy (EMBRACE Study)
NCT00409058	Not specified	COMPLETED	Teen Online Problem Solving (TOPS) - An Online Intervention Following TBI
NCT01054404	Not specified	TERMINATED	Furosemide vs Placebo for Brain Relaxation
NCT02320955	Not specified	TERMINATED	Swiss Prospective Autologous Bone Flap Resorption Study
NCT02368366	Not specified	COMPLETED	Comparative Effectiveness of Family Problem-Solving Therapy (F-PST) for Adolescent TBI
NCT02594137	Not specified	COMPLETED	A Comparison Between Two Techniques for Performing Decompressive Craniectomy
NCT02701582	Not specified	COMPLETED	Goal-Directed Intraoperative Fluid Management Using FloTrac© Monitoring in High-Risk Neurosurgical Patients
NCT03323580	Not specified	COMPLETED	Effects of Intraoperative GDFT on the Postoperative Brain Edema
NCT03957837	Not specified	COMPLETED	Optical Nerve Sheath Changes During Head Down Laparoscopy
NCT04311359	Not specified	COMPLETED	A Pharmacovigilance Study of Brain Oedema
NCT04490954	Not specified	UNKNOWN	The Accuracy of Brain Biological Electrical Impedance Tomography Screen for Supratentorial Tumors
NCT04623307	Not specified	UNKNOWN	Non-contact DCS-Speckle Multi-parameter Imaging for Neurological Diseases
NCT04834453	Not specified	COMPLETED	Correlation of Trans Cranial Doppler Ultrasound and CT Scan in Monitoring of Posttraumatic Brain Edema
NCT05051488	Not specified	UNKNOWN	Dynamic Decompressive Craniotomy
NCT05070182	Not specified	COMPLETED	Resting Energy Needs in Brain Dead Patients (reSting EneRgy nEeds iN brAin DEad Patients)
NCT06017635	Not specified	UNKNOWN	Non-invasive Monitoring and Serum Marker Study in Children With Cerebral Edema
NCT06307743	Not specified	UNKNOWN	Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke
NCT06327737	Not specified	COMPLETED	Diabetic Ketoacidosis Diagnosis and Management
NCT06526429	Not specified	COMPLETED	Local Ischemic Postconditioning in Acute Ischemic Stroke

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYDROXYETHYL STARCH 130/0.4	4	1
MANNITOL	4	1
SODIUM CHLORIDE	4	1
SORBITOL	4	1
CORTICORELIN ACETATE	3	1