Tic disorder

Summary

Tic disorder (MONDO:0002420) is a disease with 1 cohort gene and 59 clinical trials. Top therapeutic interventions include ondansetron, clonidine, and amoxicillin.

At a glance

• Cohort genes: 1
• ClinVar variants: 3
• Clinical trials: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tic disorder
Mondo ID	MONDO:0002420
MeSH	D013981
DOID	DOID:2769
ICD-10-CM	F95
SNOMED CT	568005
UMLS	C2169806
MedGen	853666
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › specific developmental disorder › tic disorder

Related subtypes (9): fetal alcohol spectrum disorder, oppositional defiant disorder, fetal nicotine spectrum disorder, communication disorder, stereotypic movement disorder, learning disability, developmental coordination disorder, conduct disorder, attention deficit-hyperactivity disorder

Subtypes (3): chronic tic disorder, transient tic disorder, Tourette syndrome

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 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
268039	46;XY;t(3;18)(q13.31;q22.1)dn		Pathogenic	criteria provided, single submitter
5664	NM_014946.4(SPAST):c.1322A>G (p.Asp441Gly)	SPAST	Pathogenic	criteria provided, multiple submitters, no conflicts
267834	46;X;t(Y;16)(q11.23;p11.2);t(6;21)(p21.3;p13)dn		Likely pathogenic	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
SPAST	Orphanet:100985	Autosomal dominant spastic paraplegia type 4

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
SPAST	HGNC:11233	ENSG00000021574	Q9UBP0	Spastin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPAST	Spastin	ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPAST	Enzyme (other)	yes	5.6.1.1	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

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
cortical plate	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPAST	284	ubiquitous	marker	cortical plate, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPAST	3,393

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPAST	Q9UBP0	7

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
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.012	SPAST
Nuclear Envelope (NE) Reassembly	1	292.8×	0.012	SPAST
Mitotic Metaphase and Anaphase	1	96.8×	0.018	SPAST
Mitotic Anaphase	1	96.8×	0.018	SPAST
M Phase	1	66.0×	0.021	SPAST
Cell Cycle, Mitotic	1	48.2×	0.024	SPAST
Cell Cycle	1	36.0×	0.028	SPAST

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
cytokinetic process	1	5617.3×	0.002	SPAST
mitotic spindle disassembly	1	5617.3×	0.002	SPAST
positive regulation of microtubule depolymerization	1	3370.4×	0.002	SPAST
central nervous system neuron axonogenesis	1	1872.4×	0.002	SPAST
mitotic nuclear membrane reassembly	1	1685.2×	0.002	SPAST
axonal transport of mitochondrion	1	1404.3×	0.002	SPAST
protein hexamerization	1	1404.3×	0.002	SPAST
microtubule severing	1	1296.3×	0.002	SPAST
exit from mitosis	1	1053.2×	0.002	SPAST
nuclear membrane reassembly	1	991.3×	0.002	SPAST
cytoskeleton-dependent cytokinesis	1	802.5×	0.002	SPAST
anterograde axonal transport	1	581.1×	0.003	SPAST
microtubule bundle formation	1	510.7×	0.003	SPAST
membrane fission	1	411.0×	0.003	SPAST
positive regulation of cytokinesis	1	401.2×	0.003	SPAST
mitotic cytokinesis	1	259.3×	0.004	SPAST
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.008	SPAST
protein homooligomerization	1	122.1×	0.008	SPAST

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aripiprazole	Phase 3 (in late-stage trials)
Tiapride	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPAST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SPAST	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SPAST	5.6.1.1	microtubule-severing ATPase

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	1	SPAST
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
SPAST	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 59.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	44
PHASE4	5
PHASE2	5
PHASE3	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00001658	PHASE4	COMPLETED	Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT05361993	PHASE4	WITHDRAWN	Efficacy of Biofeedback in the Treatment of Tic Disorder
NCT00218777	PHASE2/PHASE3	COMPLETED	Cognitive Behavior Therapy and Habit Reversal Training for the Treatment of Chronic Tic Disorders in Children
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT01727700	PHASE3	COMPLETED	Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT01727713	PHASE3	COMPLETED	Safety and Tolerability of Once-daily Oral Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06194305	PHASE2	RECRUITING	Multimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics
NCT00001359	PHASE2	COMPLETED	Preventive Measures for Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders (PANDAS Subgroup)
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT03564132	PHASE2	COMPLETED	Evaluating the Efficacy and Safety of Yi-Gan San in Children and Adolescents With Tourette’s Disorder
NCT05090943	Not specified	RECRUITING	Adult Tic Disorders Registry
NCT05317390	Not specified	RECRUITING	Clinical Validation of DystoniaNet Deep Learning Platform for Diagnosis of Isolated Dystonia
NCT05370391	Not specified	RECRUITING	Comprehensive Behavioral Intervention for Tics
NCT05390268	Not specified	RECRUITING	Mobile App-assisted Behavioral Treatment in Children and Adolescents With Tics
NCT06050369	Not specified	RECRUITING	Objective Characterizatoion of Repetitive Behaviors
NCT06408662	Not specified	RECRUITING	Remote Delivery of a Mindfulness-based Intervention for Tics
NCT06576726	Not specified	RECRUITING	Sensorimotor and Psychosocial Trajectories in Adolescents With Tic Disorder
NCT06613126	Not specified	RECRUITING	Effectiveness of Symptom Management Application on Parental Care Ability of Children With Tourette Syndrome
NCT06679790	Not specified	RECRUITING	Trajectories of Change in Tourette Syndrome
NCT06754319	Not specified	ENROLLING_BY_INVITATION	Pathogenesis of Pediatric Obsessive-compulsive Disorder: Based on the Microbiota-gut-brain Axis
NCT06924918	Not specified	ENROLLING_BY_INVITATION	Scalp Acupuncture Treatment for Chronic Tic Disorders in Children
NCT07351955	Not specified	RECRUITING	Clinical Study on a Novel Strategy of Individualized Non-Invasive Neuromodulation for the Treatment of Tic Disorders in Children
NCT00001667	Not specified	COMPLETED	Genotype/Phenotype Correlation of Movement Disorders and Other Neurological Diseases
NCT00033995	Not specified	COMPLETED	Study of Tics in Patients With Tourette’s Syndrome and Chronic Motor Tic Disorder
NCT00056420	Not specified	COMPLETED	Brain Dynamics Involved in Generating Tics and Controlling Voluntary Movement
NCT00081419	Not specified	COMPLETED	Timing of Voluntary Movement in Patients With Tourette Syndrome and Chronic Tic Disorder
NCT00675675	Not specified	COMPLETED	Neurocognitive Correlates of Behavioral Treatment for Childhood Tic Disorders
NCT00755339	Not specified	COMPLETED	Role of the Sensory Experience in Generating Motor Tics in Tourette Syndrome
NCT01019343	Not specified	COMPLETED	Physiological Investigations of Movement Disorders
NCT01177774	Not specified	COMPLETED	Assessment of Children With Tic Onset in the Past 6 Months
NCT01860300	Not specified	UNKNOWN	Efficacy of Amoxicilline/Clavulanic Acid in Patients Affected by Tic Disorder Colonized by Group A Streptococcus
NCT02144870	Not specified	UNKNOWN	Efficacy of Psychotherapy Treatment of Children With Tics
NCT02153463	Not specified	COMPLETED	Activity in Tourette Syndrome
NCT02190370	Not specified	UNKNOWN	Efficacy of a Resources Activation Treatment on Tic-symptoms
NCT02190383	Not specified	UNKNOWN	Efficacy of a Habit Reversal Treatment on Tic-symptoms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ONDANSETRON	4	3
CLONIDINE	4	2
AMOXICILLIN	4	1
ARIPIPRAZOLE	4	1
LEVETIRACETAM	4	1
NABIXIMOLS	3	1
TIAPRIDE	3	1
ETIRACETAM	2	1
LEVITIRACETAM	0	1