Corticobasal syndrome

Summary

Corticobasal syndrome (MONDO:0018696) is a disease with 2 cohort genes and 20 clinical trials. Top therapeutic interventions include glycerol phenylbutyrate, tipiracil hydrochloride, and fasudil.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 3
• Phenotypes (HPO): 22
• Clinical trials: 20

Clinical features

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001300	Parkinsonism	Very frequent (80-99%)
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0007158	Progressive extrapyramidal muscular rigidity	Very frequent (80-99%)
HP:0000726	Dementia	Frequent (30-79%)
HP:0000743	Frontal release signs	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002304	Akinesia	Frequent (30-79%)
HP:0002451	Limb dystonia	Frequent (30-79%)
HP:0003474	Somatic sensory dysfunction	Frequent (30-79%)
HP:0004305	Involuntary movements	Frequent (30-79%)
HP:0007301	Oromotor apraxia	Frequent (30-79%)
HP:0030217	Limb apraxia	Frequent (30-79%)
HP:0045084	Limb myoclonus	Frequent (30-79%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002381	Aphasia	Occasional (5-29%)
HP:0011098	Speech apraxia	Occasional (5-29%)
HP:0000708	Atypical behavior	Very rare (<1-4%)
HP:0100022	Abnormality of movement	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	corticobasal syndrome
Mondo ID	MONDO:0018696
Orphanet	454887
DOID	DOID:0081392
UMLS	C5575119
MedGen	1801322
GARD	0013168
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › corticobasal syndrome

Related subtypes (53): cerebellar ataxia, chronic tic disorder, choreatic disease, extrapyramidal and movement disease, benign shuddering attacks, transient tic disorder, essential tremor, lingual-facial-buccal dyskinesia, kuru, inherited Creutzfeldt-Jakob disease, Tourette syndrome, clonic hemifacial spasm, Huntington disease, multiple system atrophy, spinal muscular atrophy-progressive myoclonic epilepsy syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, hereditary geniospasm, tremor-nystagmus-duodenal ulcer syndrome, arthrogryposis, Lafora disease, Unverricht-Lundborg syndrome, neuronal intranuclear inclusion disease, Huntington disease-like 3, brain-lung-thyroid syndrome, myoclonus, familial, proximal myopathy with extrapyramidal signs, progressive myoclonic epilepsy type 7, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, progressive non-fluent aphasia, opsoclonus-myoclonus syndrome, isolated facial myokymia, primary orthostatic tremor, familial congenital mirror movements, neuroacanthocytosis, behavioral variant of frontotemporal dementia, frontotemporal dementia with motor neuron disease, hyperekplexia, intellectual disability-hyperkinetic movement-truncal ataxia syndrome, neurodegeneration with brain iron accumulation, Huntington disease-like syndrome due to C9ORF72 expansions, variably protease-sensitive prionopathy, sensorineural hearing loss-early graying-essential tremor syndrome, progressive supranuclear palsy, Sandifer syndrome, psychogenic movement disorders, epilepsy with myoclonic absences, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, childhood-onset benign chorea with striatal involvement, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, PRRT2-associated paroxysmal movement disorder, SLC6A3-related dopamine transporter deficiency syndrome, dyskinesia with orofacial involvement, autosomal dominant, complex movement disorder with or without neurodevelopmental features

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:

1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
619188	NM_013254.4(TBK1):c.2107G>T (p.Glu703Ter)	TBK1	Likely pathogenic	no assertion criteria provided
870548	NM_001110.4(ADAM10):c.359T>C (p.Ile120Thr)	ADAM10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870549	NM_001330683.2(TTC3):c.5557G>A (p.Val1853Met)	LOC125418073	Uncertain significance	criteria provided, single submitter

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
TBK1	Orphanet:1930	Herpes simplex virus encephalitis
TBK1	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TBK1	Orphanet:803	Amyotrophic lateral sclerosis
ADAM10	Orphanet:178307	Reticulate acropigmentation of Kitamura

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
TBK1	HGNC:11584	ENSG00000183735	Q9UHD2	Serine/threonine-protein kinase TBK1	clinvar
ADAM10	HGNC:188	ENSG00000137845	O14672	Disintegrin and metalloproteinase domain-containing protein 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBK1	Serine/threonine-protein kinase TBK1	Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents.
ADAM10	Disintegrin and metalloproteinase domain-containing protein 10	Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis.

Protein-family classification

Druggable: 2 · 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
Protease	1	18.3×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBK1	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
ADAM10	Protease	yes	3.4.24.81	Peptidase_M12B, Disintegrin_dom, MetalloPept_cat_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
calcaneal tendon	1
colonic epithelium	1
lateral nuclear group of thalamus	1
amniotic fluid	1
stromal cell of endometrium	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBK1	284	ubiquitous	marker	colonic epithelium, calcaneal tendon, lateral nuclear group of thalamus
ADAM10	298	ubiquitous	marker	stromal cell of endometrium, amniotic fluid, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBK1	5,476
ADAM10	3,603

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBK1	Q9UHD2	25
ADAM10	O14672	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. 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
STAT6-mediated induction of chemokines	1	1903.3×	0.013	TBK1
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	1427.5×	0.013	ADAM10
IRF3 mediated activation of type 1 IFN	1	951.7×	0.013	TBK1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	815.7×	0.013	ADAM10
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	634.4×	0.013	ADAM10
ZBP1(DAI) mediated induction of type I IFNs	1	519.1×	0.013	TBK1
STING mediated induction of host immune responses	1	519.1×	0.013	TBK1
Mitophagy	1	519.1×	0.013	TBK1
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	519.1×	0.013	ADAM10
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	475.8×	0.013	TBK1
IRF3-mediated induction of type I IFN	1	407.9×	0.013	TBK1
TICAM1-dependent activation of IRF3/IRF7	1	407.9×	0.013	TBK1
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	380.7×	0.013	ADAM10
Regulation of innate immune responses to cytosolic DNA	1	380.7×	0.013	TBK1
TRAF3-dependent IRF activation pathway	1	380.7×	0.013	TBK1
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	1	380.7×	0.013	TBK1
Innate Immune System	2	25.5×	0.013	TBK1, ADAM10
Signaling by NOTCH2	1	356.9×	0.013	ADAM10
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	300.5×	0.014	TBK1
Interleukin-37 signaling	1	259.6×	0.014	TBK1
Signaling by NOTCH3	1	259.6×	0.014	ADAM10
Signaling by NOTCH4	1	248.3×	0.014	ADAM10
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	237.9×	0.014	ADAM10
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	219.6×	0.014	ADAM10
TNFR1-induced proapoptotic signaling	1	219.6×	0.014	TBK1
TNF signaling	1	211.5×	0.014	TBK1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1	203.9×	0.014	ADAM10
Signaling by NOTCH1 in Cancer	1	203.9×	0.014	ADAM10
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1	203.9×	0.014	ADAM10
TRAF6 mediated IRF7 activation	1	190.3×	0.014	TBK1

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
constitutive protein ectodomain proteolysis	1	8426.0×	0.004	ADAM10
regulation of vasculature development	1	8426.0×	0.004	ADAM10
epidermal growth factor receptor ligand maturation	1	4213.0×	0.004	ADAM10
dendritic cell proliferation	1	2808.7×	0.004	TBK1
protein catabolic process at postsynapse	1	2808.7×	0.004	ADAM10
negative regulation of gene expression	2	69.1×	0.004	TBK1, ADAM10
cGAS/STING signaling pathway	1	1685.2×	0.005	TBK1
postsynapse organization	1	1203.7×	0.005	ADAM10
positive regulation of xenophagy	1	1053.2×	0.005	TBK1
positive regulation of TORC2 signaling	1	1053.2×	0.005	TBK1
monocyte activation	1	936.2×	0.005	ADAM10
pore complex assembly	1	936.2×	0.005	ADAM10
regulation of type I interferon production	1	842.6×	0.006	TBK1
T follicular helper cell differentiation	1	702.2×	0.006	TBK1
amyloid precursor protein catabolic process	1	601.9×	0.007	ADAM10
positive regulation of T cell chemotaxis	1	561.7×	0.007	ADAM10
positive regulation of tumor necrosis factor-mediated signaling pathway	1	526.6×	0.007	ADAM10
cytoplasmic pattern recognition receptor signaling pathway	1	443.5×	0.007	TBK1
peptidyl-threonine phosphorylation	1	443.5×	0.007	TBK1
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	443.5×	0.007	ADAM10
regulation of Notch signaling pathway	1	421.3×	0.007	ADAM10
positive regulation of type I interferon-mediated signaling pathway	1	421.3×	0.007	TBK1
membrane protein ectodomain proteolysis	1	324.1×	0.008	ADAM10
positive regulation of interferon-alpha production	1	324.1×	0.008	TBK1
response to tumor necrosis factor	1	312.1×	0.008	ADAM10
positive regulation of macroautophagy	1	263.3×	0.008	TBK1
toll-like receptor 4 signaling pathway	1	263.3×	0.008	TBK1
regulation of postsynapse organization	1	263.3×	0.008	ADAM10
adherens junction organization	1	255.3×	0.008	ADAM10
peptidyl-serine phosphorylation	1	247.8×	0.008	TBK1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
TBK1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBK1	38	4
ADAM10	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1
MILCICLIB	2	TBK1
TOZASERTIB	2	TBK1
UCN-01	2	TBK1
ILOMASTAT	2	ADAM10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TBK1	475	Binding:473, Functional:2
ADAM10	64	Binding:60, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAM10	3.4.24.81	ADAM10 endopeptidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TBK1	475

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

30 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)
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1
MILCICLIB	2	TBK1
TOZASERTIB	2	TBK1
UCN-01	2	TBK1
ILOMASTAT	2	ADAM10

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TBK1
B	Phased (≥1) drug, not yet approved	1	ADAM10
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: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	15
PHASE2	4
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05983588	PHASE2	ACTIVE_NOT_RECRUITING	PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS)
NCT06162013	PHASE2	RECRUITING	The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism
NCT00273897	PHASE2	COMPLETED	Electrical Polarization of the Brain in Corticobasal Syndrome
NCT04734379	PHASE2	UNKNOWN	Rho Kinase (ROCK) Inhibitor in Tauopathies - 1
NCT02133846	PHASE1	COMPLETED	Safety Study of TPI-287 to Treat CBS and PSP
NCT02964637	Not specified	RECRUITING	Diagnosing Frontotemporal Lobar Degeneration
NCT04715399	Not specified	RECRUITING	UPenn Observational Research Repository on Neurodegenerative Disease
NCT05073471	Not specified	ACTIVE_NOT_RECRUITING	Music and Brain Stimulation for Upper Extremity Performance in Patients With Corticobasal Syndrome
NCT05653778	Not specified	RECRUITING	Scrambler Therapy for Corticobasal Syndrome-Associated Pain
NCT06529744	Not specified	RECRUITING	Improving Prognostic Confidence in Neurodegenerative Diseases Causing Dementia Using Peripheral Biomarkers and Integrative Modeling
NCT06613204	Not specified	RECRUITING	STELLA-FTD: Examination of a Behavior Change Intervention for FTD Family Care Partners
NCT06647641	Not specified	RECRUITING	The CurePSP Genetics Program
NCT06870838	Not specified	ACTIVE_NOT_RECRUITING	Neuroinflammation in FTLD
NCT07000851	Not specified	RECRUITING	Imaging Studies in Corticobasal Syndrome
NCT07333898	Not specified	NOT_YET_RECRUITING	Digital Measurements of Motor and Voice Functions in FTD
NCT07569367	Not specified	NOT_YET_RECRUITING	A Wearable Sensor Platform for Remote Monitoring of Individuals on the Frontotemporal Dementia Spectrum
NCT02365922	Not specified	COMPLETED	Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)
NCT02966145	Not specified	COMPLETED	4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2
NCT03552484	Not specified	COMPLETED	In-Home Care for Patients With PSP and Related Disorders
NCT06224920	Not specified	COMPLETED	Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer’s Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GLYCEROL PHENYLBUTYRATE	4	1
TIPIRACIL HYDROCHLORIDE	4	1
FASUDIL	3	1
NICOTINAMIDE RIBOSIDE	3	1