Basal ganglia disorder

Summary

Basal ganglia disorder (MONDO:0003996) is a disease with 2 cohort genes and 14 clinical trials. Top therapeutic interventions include isoxaflutole.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal ganglia disorder
Mondo ID	MONDO:0003996
EFO	EFO:0009533
MeSH	D001480
DOID	DOID:679
SNOMED CT	70835005
UMLS	C4520981
MedGen	1619147
Anatomy (UBERON)	UBERON:0010011
Is cancer (heuristic)	no

Also known as: basal ganglia disease · collection of basal ganglia disease · collection of basal ganglia disease or disorder · disease of basal ganglia · disease of collection of basal ganglia · disease or disorder of collection of basal ganglia · disorder of basal ganglia · disorder of collection of basal ganglia

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

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, 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

Subtypes (4): basal ganglia cerebrovascular disorder, bilateral striopallidodentate calcinosis, biotin-responsive basal ganglia disease, parkinsonian disorder

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
375378	NM_018897.3(DNAH7):c.10753T>C (p.Phe3585Leu)	DNAH7	Pathogenic	no assertion criteria provided
137622	NM_022168.4(IFIH1):c.2336G>A (p.Arg779His)	IFIH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAH7	Orphanet:244	Primary ciliary dyskinesia
IFIH1	Orphanet:51	Aicardi-Goutières syndrome
IFIH1	Orphanet:689231	IFIH1-related hereditary spastic paraplegia
IFIH1	Orphanet:85191	Singleton-Merten dysplasia

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
DNAH7	HGNC:18661	ENSG00000118997	Q8WXX0	Dynein axonemal heavy chain 7	clinvar
IFIH1	HGNC:18873	ENSG00000115267	Q9BYX4	Interferon-induced helicase C domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAH7	Dynein axonemal heavy chain 7	Force generating protein that plays an important role in respiratory cilia and sperm flagella beating.
IFIH1	Interferon-induced helicase C domain-containing protein 1	Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAH7	Other/Unknown	no		EF_hand_dom, AAA+_ATPase, Dhc_D6_P-loop
IFIH1	Other/Unknown	no		Helicase_C-like, Helicase/UvrB_N, DEATH-like_dom_sf

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
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1
jejunal mucosa	1
palpebral conjunctiva	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAH7	212	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
IFIH1	276	ubiquitous	marker	palpebral conjunctiva, parotid gland, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFIH1	3,706
DNAH7	1,537

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFIH1	Q9BYX4	9
DNAH7	Q8WXX0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 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
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	878.5×	0.005	IFIH1
TRAF3-dependent IRF activation pathway	1	761.3×	0.005	IFIH1
Modulation of host responses by IFN-stimulated genes	1	601.0×	0.005	IFIH1
TRAF6 mediated NF-kB activation	1	456.8×	0.005	IFIH1
TRAF6 mediated IRF7 activation	1	380.7×	0.005	IFIH1
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.005	IFIH1
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.005	IFIH1
Evasion by RSV of host interferon responses	1	326.3×	0.005	IFIH1
Ovarian tumor domain proteases	1	278.5×	0.005	IFIH1
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.005	IFIH1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	253.8×	0.005	IFIH1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	IFIH1
Ub-specific processing proteases	1	53.1×	0.019	IFIH1

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
regulation of type III interferon production	1	4213.0×	0.004	IFIH1
detection of virus	1	2106.5×	0.004	IFIH1
MDA-5 signaling pathway	1	2106.5×	0.004	IFIH1
positive regulation of response to cytokine stimulus	1	1203.7×	0.005	IFIH1
cilium-dependent cell motility	1	702.2×	0.006	DNAH7
cellular response to exogenous dsRNA	1	526.6×	0.006	IFIH1
cytoplasmic pattern recognition receptor signaling pathway	1	443.5×	0.006	IFIH1
inner dynein arm assembly	1	443.5×	0.006	DNAH7
protein complex oligomerization	1	337.0×	0.006	IFIH1
cilium movement involved in cell motility	1	337.0×	0.006	DNAH7
positive regulation of interferon-alpha production	1	324.1×	0.006	IFIH1
cilium movement	1	195.9×	0.009	DNAH7
positive regulation of interferon-beta production	1	195.9×	0.009	IFIH1
negative regulation of viral genome replication	1	187.2×	0.009	IFIH1
type I interferon-mediated signaling pathway	1	172.0×	0.009	IFIH1
protein sumoylation	1	162.0×	0.009	IFIH1
antiviral innate immune response	1	113.9×	0.012	IFIH1
cellular response to virus	1	100.3×	0.013	IFIH1
positive regulation of interleukin-6 production	1	83.4×	0.014	IFIH1
positive regulation of tumor necrosis factor production	1	76.6×	0.015	IFIH1
response to virus	1	72.0×	0.015	IFIH1
defense response to virus	1	34.7×	0.030	IFIH1
innate immune response	1	16.8×	0.059	IFIH1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNAH7	0	0
IFIH1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
IFIH1	1	Binding:1

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	DNAH7, IFIH1

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)
DNAH7	0	—
IFIH1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE4	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT02696603	Not specified	ACTIVE_NOT_RECRUITING	Mobile Parkinson Observatory for Worldwide, Evidence-based Research (mPower)
NCT04985539	Not specified	ACTIVE_NOT_RECRUITING	The Personalized Parkinson Project De Novo Cohort
NCT06193252	Not specified	RECRUITING	Slow-SPEED-NL: Slowing Parkinson’s Early Through Exercise Dosage-Netherlands
NCT06534177	Not specified	NOT_YET_RECRUITING	Digital Diagnostics and Intervention Services for Parkinson’s Disease
NCT06841718	Not specified	ENROLLING_BY_INVITATION	Investigating the Neural Signature of Freezing of Gait in Parkinson’s Disease
NCT06993142	Not specified	NOT_YET_RECRUITING	Slow-SPEED: Slowing Parkinson’s Early Through Exercise Dosage
NCT07187843	Not specified	RECRUITING	Study of Axial and Cognitive Symptoms and Biomarkers of Neurodegeneration in Brain-first and Body-first PD
NCT07324330	Not specified	RECRUITING	Slowing Cognitive Decline in Alpha-synucleinopathies by Enhancing Physical Activity
NCT01905995	Not specified	UNKNOWN	Basal Ganglia Local Field Potentials in Gait and Speech
NCT02823158	Not specified	TERMINATED	Bilateral Pallidal Stimulation in Patients With Advanced Parkinson’s Disease-LATESTIM
NCT05452655	Not specified	UNKNOWN	Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson’s Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ISOXAFLUTOLE	2	1