Childhood-onset benign chorea with striatal involvement

Summary

Childhood-onset benign chorea with striatal involvement (MONDO:0044332) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0002072	Chorea	Very frequent (80-99%)
HP:0010994	Abnormal corpus striatum morphology	Frequent (30-79%)
HP:0031206	Striatal T2 hyperintensity	Frequent (30-79%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0002548	Parkinsonism with favorable response to dopaminergic medication	Occasional (5-29%)
HP:0000726	Dementia	Excluded (0%)
HP:0002194	Delayed gross motor development	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood-onset benign chorea with striatal involvement
Mondo ID	MONDO:0044332
Orphanet	494541
UMLS	C5567463
MedGen	1798886
GARD	0017906
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › childhood-onset benign chorea with striatal involvement

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, corticobasal syndrome, 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 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
PDE10A	Strong	Autosomal recessive	dyskinesia, limb and orofacial, infantile-onset	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDE10A	Orphanet:494526	Infantile-onset generalized dyskinesia with orofacial involvement
PDE10A	Orphanet:494541	Childhood-onset benign chorea with striatal involvement

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
PDE10A	HGNC:8772	ENSG00000112541	Q9Y233	cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDE10A	cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10A	Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDE10A	Transcription factor	no	3.1.4.17	PDEase_catalytic_dom, GAF, HD/PDEase_dom

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
adrenal tissue	1
cartilage tissue	1
left uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDE10A	219	broad	marker	adrenal tissue, left uterine tube, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDE10A	1,318

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDE10A	Q9Y233	359

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
cGMP effects	1	713.8×	0.003	PDE10A
G alpha (s) signalling events	1	73.2×	0.014	PDE10A

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
cGMP catabolic process	1	3370.4×	7e-04	PDE10A
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	3370.4×	7e-04	PDE10A
negative regulation of receptor guanylyl cyclase signaling pathway	1	2808.7×	7e-04	PDE10A
cAMP catabolic process	1	1872.4×	8e-04	PDE10A
negative regulation of cAMP/PKA signal transduction	1	601.9×	0.002	PDE10A
signal transduction	1	16.1×	0.062	PDE10A

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
PDE10A	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDE10A	16	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARDENAFIL	4	PDE10A
SILDENAFIL	4	PDE10A
CINCHOPHEN	4	PDE10A
DIPYRIDAMOLE	4	PDE10A
PAPAVERINE	3	PDE10A
OXYCINCHOPHEN	2	PDE10A
ZAPRINAST	2	PDE10A
PF-06835919	2	PDE10A
MK-8189	2	PDE10A
MARDEPODECT	2	PDE10A
PAPAVERINE HYDROCHLORIDE	2	PDE10A
PF-04217903	1	PDE10A
JNJ-42396302	1	PDE10A
LENRISPODUN PHOSPHATE	1	PDE10A
PBF-999	1	PDE10A
AZD-7687	1	PDE10A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PDE10A	357	Binding:345, ADMET:9, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDE10A	3.1.4.17	3’,5’-cyclic-nucleotide phosphodiesterase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PDE10A	357

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

16 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)
VARDENAFIL	4	PDE10A
SILDENAFIL	4	PDE10A
CINCHOPHEN	4	PDE10A
DIPYRIDAMOLE	4	PDE10A
PAPAVERINE	3	PDE10A
OXYCINCHOPHEN	2	PDE10A
ZAPRINAST	2	PDE10A
PF-06835919	2	PDE10A
MK-8189	2	PDE10A
MARDEPODECT	2	PDE10A
PAPAVERINE HYDROCHLORIDE	2	PDE10A
PF-04217903	1	PDE10A
JNJ-42396302	1	PDE10A
LENRISPODUN PHOSPHATE	1	PDE10A
PBF-999	1	PDE10A
AZD-7687	1	PDE10A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDE10A
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: 0.