Combined dystonia

Summary

Combined dystonia (MONDO:0020065) is a disease (an umbrella term covering 10 Mondo subtypes) with 1 cohort gene and 1 clinical trial.

At a glance

• Umbrella term: 10 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	combined dystonia
Mondo ID	MONDO:0020065
Orphanet	98203
UMLS	C5680244
MedGen	1842879
GARD	0019432
Is cancer (heuristic)	no

Also known as: dystonia-plus syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › combined dystonia

Related subtypes (23): lymphatic malformation 5, Woodhouse-Sakati syndrome, severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome, torsion dystonia 7, developmental malformations-deafness-dystonia syndrome, dopa-responsive dystonia due to sepiapterin reductase deficiency, ataxia - oculomotor apraxia type 4, striatonigral degeneration, childhood-onset, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, dystonia 28, childhood-onset, isolated dystonia, dystonia 30, dystonia 31, dystonia 32, dystonia 33, dystonia 34, myoclonic, dystonia 35, childhood-onset, familial idiopathic torsion dystonia, dystonia, focal, task-specific, dystonia 37, early-onset, with striatal lesions, dystonia 22, juvenile-onset, dystonia 22, adult-onset, autosomal dominant dopa-responsive dystonia

Subtypes (10): myoclonus-dystonia syndrome, dystonia 12, X-linked dystonia-parkinsonism, dystonia 16, parkinsonism-dystonia, infantile, paroxysmal dystonia, infantile epileptic-dyskinetic encephalopathy, ataxia - telangiectasia variant, combined cervical dystonia, dystonia-aphonia 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DRD2	Moderate	Autosomal dominant	combined dystonia

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DRD2	Orphanet:36899	Myoclonus-dystonia 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
DRD2	HGNC:3023	ENSG00000149295	P14416	D(2) dopamine receptor	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DRD2	D(2) dopamine receptor	Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DRD2	GPCR	yes		GPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D2_rcpt

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
nucleus accumbens	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DRD2	159	broad	yes	putamen, nucleus accumbens, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRD2	3,148

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DRD2	P14416	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Dopamine receptors	1	2284.0×	4e-04	DRD2

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 circadian sleep/wake cycle, sleep	1	16852.0×	0.002	DRD2
orbitofrontal cortex development	1	8426.0×	0.002	DRD2
regulation of locomotion involved in locomotory behavior	1	8426.0×	0.002	DRD2
positive regulation of glial cell-derived neurotrophic factor production	1	8426.0×	0.002	DRD2
nervous system process involved in regulation of systemic arterial blood pressure	1	5617.3×	0.002	DRD2
response to inactivity	1	5617.3×	0.002	DRD2
acid secretion	1	5617.3×	0.002	DRD2
positive regulation of dopamine uptake involved in synaptic transmission	1	5617.3×	0.002	DRD2
negative regulation of dopamine receptor signaling pathway	1	5617.3×	0.002	DRD2
negative regulation of dopamine secretion	1	4213.0×	0.002	DRD2
response to histamine	1	4213.0×	0.002	DRD2
negative regulation of dephosphorylation	1	4213.0×	0.002	DRD2
positive regulation of renal sodium excretion	1	4213.0×	0.002	DRD2
regulation of synapse structural plasticity	1	4213.0×	0.002	DRD2
negative regulation of cellular response to hypoxia	1	4213.0×	0.002	DRD2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	3370.4×	0.002	DRD2
beta-arrestin-dependent dopamine receptor signaling pathway	1	3370.4×	0.002	DRD2
cerebral cortex GABAergic interneuron migration	1	2808.7×	0.002	DRD2
auditory behavior	1	2808.7×	0.002	DRD2
adenohypophysis development	1	2407.4×	0.002	DRD2
branching morphogenesis of a nerve	1	2407.4×	0.002	DRD2
regulation of dopamine uptake involved in synaptic transmission	1	2407.4×	0.002	DRD2
hyaloid vascular plexus regression	1	2407.4×	0.002	DRD2
phospholipase C-activating dopamine receptor signaling pathway	1	2106.5×	0.002	DRD2
regulation of potassium ion transport	1	1872.4×	0.002	DRD2
dopamine uptake involved in synaptic transmission	1	1872.4×	0.002	DRD2
positive regulation of growth hormone secretion	1	1872.4×	0.002	DRD2
G protein-coupled receptor internalization	1	1685.2×	0.002	DRD2
neuron-neuron synaptic transmission	1	1685.2×	0.002	DRD2
negative regulation of synaptic transmission, glutamatergic	1	1685.2×	0.002	DRD2

Therapeutics

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
DRD2	CABERGOLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRD2	298	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABERGOLINE	4	DRD2
APOMORPHINE	4	DRD2
HALOPERIDOL	4	DRD2
ROPINIROLE	4	DRD2
DOPAMINE	4	DRD2
BEPRIDIL	4	DRD2
CLOTRIMAZOLE	4	DRD2
METHYSERGIDE	4	DRD2
OXAPROZIN	4	DRD2
ACETOPHENAZINE	4	DRD2
IMIPRAMINE	4	DRD2
DROPERIDOL	4	DRD2
ARIPIPRAZOLE	4	DRD2
AMOXAPINE	4	DRD2
IDARUBICIN	4	DRD2
SAQUINAVIR	4	DRD2
PONATINIB	4	DRD2
DESLORATADINE	4	DRD2
DULOXETINE	4	DRD2
BETAMETHASONE DIPROPIONATE	4	DRD2
TIOCONAZOLE	4	DRD2
NEFAZODONE HYDROCHLORIDE	4	DRD2
DIHYDROERGOTAMINE MESYLATE	4	DRD2
FEXOFENADINE HYDROCHLORIDE	4	DRD2
AZELASTINE HYDROCHLORIDE	4	DRD2
HALOPERIDOL DECANOATE	4	DRD2
THIOTHIXENE	4	DRD2
ARMODAFINIL	4	DRD2
BENZTROPINE	4	DRD2
PROPIOMAZINE	4	DRD2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DRD2	2,636	Binding:2064, Functional:517, ADMET:54, Unclassified:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DRD2	2,636

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

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)
CABERGOLINE	4	DRD2
APOMORPHINE	4	DRD2
HALOPERIDOL	4	DRD2
ROPINIROLE	4	DRD2
DOPAMINE	4	DRD2
BEPRIDIL	4	DRD2
CLOTRIMAZOLE	4	DRD2
METHYSERGIDE	4	DRD2
OXAPROZIN	4	DRD2
ACETOPHENAZINE	4	DRD2
IMIPRAMINE	4	DRD2
DROPERIDOL	4	DRD2
ARIPIPRAZOLE	4	DRD2
AMOXAPINE	4	DRD2
IDARUBICIN	4	DRD2
SAQUINAVIR	4	DRD2
PONATINIB	4	DRD2
DESLORATADINE	4	DRD2
DULOXETINE	4	DRD2
BETAMETHASONE DIPROPIONATE	4	DRD2
TIOCONAZOLE	4	DRD2
NEFAZODONE HYDROCHLORIDE	4	DRD2
DIHYDROERGOTAMINE MESYLATE	4	DRD2
FEXOFENADINE HYDROCHLORIDE	4	DRD2
AZELASTINE HYDROCHLORIDE	4	DRD2
HALOPERIDOL DECANOATE	4	DRD2
THIOTHIXENE	4	DRD2
ARMODAFINIL	4	DRD2
BENZTROPINE	4	DRD2
PROPIOMAZINE	4	DRD2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DRD2
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06999096	Not specified	RECRUITING	Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia