Brain disorder

Summary

Brain disorder (MONDO:0005560) is a disease (an umbrella term covering 71 Mondo subtypes) with 1 cohort gene (4 GWAS associations across 19 studies) and 255 clinical trials. Top therapeutic interventions include foscarnet, donanemab, and ezogabine.

At a glance

• Umbrella term: 71 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 4
• ClinVar variants: 2
• Clinical trials: 255

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain disorder
Mondo ID	MONDO:0005560
EFO	EFO:0005774
MeSH	D001927
DOID	DOID:936
NCIT	C96413
SNOMED CT	81308009
UMLS	C0006111
MedGen	14214
Anatomy (UBERON)	UBERON:0000955
Is cancer (heuristic)	no

Also known as: brain disease · brain disease or disorder · disease of brain · disease or disorder of brain · disorder of brain · encephalopathy

Data availability: 2 ClinVar variants · 4 GWAS associations (19 studies).

Disease family

An umbrella term covering 71 Mondo subtypes.

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

Related subtypes (18): autoimmune disorder of central nervous system, autonomic nervous system disorder, optic nerve disorder, spinal cord disorder, high pressure neurological syndrome, central nervous system vasculitis, encephalomyelitis, neurodegenerative disease, central nervous system neoplasm, palsy, trigeminal neuralgia, infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly, sporadic fetal brain disruption sequence, congenital narrowing of cervical spinal canal, central nervous system infectious disorder, cerebrospinal fluid leak, SPAST-related motor disorder, tinnitus

Subtypes (71): 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, brain edema, 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

4 GWAS associations across 19 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs738409	1e-14	PNPLA3	C	0.14
rs3747207	4e-14	PNPLA3	G	0.12
rs183411298	8e-12	TARID	C	2.72
rs150694450	2e-08	VLDLR-AS1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475838	Verma A	2024	8,512	432,582	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473369	UK Biobank Whole-Genome Sequencing Consortium	2025	6,826	451,614	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90477564	Verma A	2024	2,690	116,332	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480026	Verma A	2024	2,690	116,332	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079858	Backman JD	2021	2,591	383,973	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083844	Backman JD	2021	2,591	383,973	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90477569	Verma A	2024	2,582	442,465	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435933	Zhou W	2018	1,426	395,209	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90477563	Verma A	2024	1,061	57,658	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477568	Verma A	2024	769	119,325	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	3

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	1

Functional consequences

Consequence	Count
intergenic_variant	2
missense_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs738409	22	43928847	C>A,G,T	0.225	missense_variant	PNPLA3	1e-14	Tier 1: coding
rs3747207	22	43928975	G>A,C,T	0.219	intron_variant	PNPLA3	4e-14	Tier 4: intronic/intergenic
rs183411298	6	133899052	C>A,T	0.001	intergenic_variant	TARID	8e-12	Tier 4: intronic/intergenic
rs150694450	9	2593646	G>A		intergenic_variant	VLDLR-AS1	2e-08	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072187	NM_024928.5(STN1):c.707T>C (p.Leu236Pro)	STN1	Likely pathogenic	criteria provided, single submitter
1346494	NM_024928.5(STN1):c.894dup (p.Asp299fs)	STN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STN1	Orphanet:2032	Idiopathic pulmonary fibrosis
STN1	Orphanet:313838	Coats plus syndrome

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
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STN1	CST complex subunit STN1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1

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
esophagus mucosa	1
lower esophagus mucosa	1
oral cavity	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STN1	284	ubiquitous	marker	lower esophagus mucosa, oral cavity, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STN1	1,863

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STN1	Q9H668	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Telomere C-strand synthesis initiation	1	815.7×	0.004	STN1
Telomere C-strand (Lagging Strand) Synthesis	1	761.3×	0.004	STN1
Extension of Telomeres	1	601.0×	0.004	STN1
Polymerase switching on the C-strand of the telomere	1	423.0×	0.004	STN1
Telomere Maintenance	1	368.4×	0.004	STN1
Chromosome Maintenance	1	211.5×	0.006	STN1
Cell Cycle	1	36.0×	0.028	STN1

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
telomere maintenance via telomere lengthening	1	1872.4×	0.002	STN1
telomere capping	1	1296.3×	0.002	STN1
negative regulation of telomere maintenance via telomerase	1	732.7×	0.002	STN1
positive regulation of DNA replication	1	581.1×	0.002	STN1
telomere maintenance	1	267.5×	0.004	STN1

Therapeutics

Drugs indicated for this disease

1 approved, 13 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Levocarnitine	Approved (phase 4)
Allopurinol	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Chloral Hydrate	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Lactobacillus Acidophilus	Phase 3 (in late-stage trials)
Lactulose	Phase 3 (in late-stage trials)
Lapatinib	Phase 3 (in late-stage trials)
Mannitol	Phase 3 (in late-stage trials)
Nifuroxazide	Phase 3 (in late-stage trials)
Nitazoxanide	Phase 3 (in late-stage trials)
Ornithine	Phase 3 (in late-stage trials)
Rifaximin	Phase 3 (in late-stage trials)
Trastuzumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Charcoal, Activated, Chloroquine, Darbepoetin Alfa, Dasatinib Anhydrous, Metronidazole, Pentoxifylline, Sacituzumab Govitecan, Sildenafil, Sodium Benzoate, Sodium Phenylacetate, Temozolomide, Vitamin E, Vorinostat.

Drug target analysis

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

Druggability breadth: 0 of 1 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
STN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	STN1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
STN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 255.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	206
PHASE2	16
PHASE4	9
PHASE3	8
PHASE1	7
PHASE1/PHASE2	6
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05812755	PHASE4	RECRUITING	SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery
NCT00570973	PHASE4	COMPLETED	Band Ligation Versus Transjugular Intrahepatic Portosystemic Stent Shunt (TIPS) in Cirrhotics With Recurrent Variceal Bleeding Non Responding to Medical Therapy
NCT01613417	PHASE4	COMPLETED	Comparison of Prohance® With Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT02070380	PHASE4	COMPLETED	Crossover Comparison of MultiHance and Dotarem
NCT02776189	PHASE4	COMPLETED	Dexmedetomidine Verses Propofol for Paediatric MRI Brain
NCT02951559	PHASE4	UNKNOWN	SOLFAMU Study of Nasal Brushing Collected OLFActory MUcosa Samples in the Diagnosis of Human Encephalopathies
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT06244823	PHASE4	UNKNOWN	The FreMRI Study: Advanced MRI on Migraine Patients Treated With Fremanezumab
NCT05395195	PHASE3	RECRUITING	Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)
NCT05508789	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 5)
NCT05738486	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 6)
NCT05892510	PHASE2/PHASE3	RECRUITING	Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke
NCT06447701	PHASE3	NOT_YET_RECRUITING	Interleukin-6 Receptor Inhibition for Symptomatic Intracranial Atherosclerosis
NCT00216502	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine in Patients With Alzheimer’s Disease
NCT00240695	PHASE3	COMPLETED	A Follow-up Study to Assess Safety and Tolerability of Galantamine Treatment in Individuals With Mild Cognitive Impairment
NCT01414582	PHASE2/PHASE3	UNKNOWN	Transcranial Stimulation and Motor Training in Stroke Rehabilitation
NCT04639310	PHASE3	TERMINATED	XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
NCT04912856	PHASE3	TERMINATED	An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE
NCT04755920	PHASE2	RECRUITING	SGM-101 in Colorectal Brain Metastases.
NCT05386108	PHASE1/PHASE2	RECRUITING	Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+/HER-2- Breast Cancer
NCT06712004	PHASE2	RECRUITING	A Dose-Response Controlled Trial of Bevifibatide for Acute Ischemic Stroke
NCT00000982	PHASE2	COMPLETED	A Study of Azidothymidine in HIV-Infected Children
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00764049	PHASE1/PHASE2	COMPLETED	Single Pass Albumin Dialysis in Patients With Cirrhosis
NCT00862459	PHASE2	COMPLETED	Dose Finding Study of Gadavist in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
NCT03295786	PHASE1/PHASE2	COMPLETED	Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease
NCT03448159	PHASE2	COMPLETED	Fluoxetine Opens Window to Improve Motor Recovery After Stroke
NCT03775538	PHASE1/PHASE2	COMPLETED	Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease. Extension to HP-CD-CL-2002 Clinical Study
NCT03926351	PHASE2	UNKNOWN	High Dose Omega 3 in People at Risk for Dementia
NCT04228653	PHASE1/PHASE2	UNKNOWN	Long-Term Follow-up Safety After DDS Implantation With/Without CDNF Infusions
NCT04445831	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer’s Disease
NCT04640077	PHASE2	COMPLETED	A Follow-On Study of Donanemab (LY3002813) With Video Assessments in Participants With Alzheimer’s Disease (TRAILBLAZER-EXT)
NCT04937452	PHASE2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT04970355	PHASE2	COMPLETED	Efficacy of Erenumab in Chronic Cluster Headache
NCT05318976	PHASE2	COMPLETED	A Study of XPro1595 in Patients With Early Alzheimer’s Disease With Biomarkers of Inflammation
NCT05321498	PHASE2	WITHDRAWN	Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation
NCT05375240	PHASE2	UNKNOWN	Propranolol on Post Stroke Immune Status and Infection
NCT05522387	PHASE2	TERMINATED	An Open-Label Extension of XPro1595 in Patients With Alzheimer’s Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FOSCARNET	4	4
DONANEMAB	4	3
EZOGABINE	4	2
GADOTERATE MEGLUMINE	4	2
GALANTAMINE HYDROBROMIDE	4	2
LEVODOPA	4	2
ACIPIMOX	4	1
CEFTRIAXONE	4	1
DEXMEDETOMIDINE	4	1
DIDANOSINE	4	1
ELACESTRANT	4	1
ERENUMAB	4	1
FLORBETABEN F18	4	1
GADOBENATE DIMEGLUMINE	4	1
GADOBUTROL	4	1
GADOTERIDOL	4	1
GANCICLOVIR	4	1
OLIVE OIL	4	1
ROTIGOTINE	4	1
VERICIGUAT	4	1
XENON	4	1
PRELADENANT	3	2
CARBON DIOXIDE	3	1
LEUCINE	3	1
OMEGA-3 FATTY ACIDS	3	1
VELIPARIB	3	1
PEGIPANERMIN	2	3
AMLINTIDE	2	2
ADRENOMEDULLIN	2	1
ISOXAFLUTOLE	2	1