Dystonia 23

Summary

Dystonia 23 (MONDO:0013928) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 7
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000473	Torticollis	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0001618	Dysphonia	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0002346	Head tremor	Frequent (30-79%)
HP:0002356	Writer’s cramp	Frequent (30-79%)
HP:0002530	Axial dystonia	Frequent (30-79%)
HP:0004373	Focal dystonia	Frequent (30-79%)
HP:0012179	Craniofacial dystonia	Frequent (30-79%)
HP:0012893	Neck muscle hypertrophy	Frequent (30-79%)
HP:0200085	Limb tremor	Frequent (30-79%)
HP:0002883	Hyperventilation	Occasional (5-29%)
HP:0005115	Supraventricular arrhythmia	Occasional (5-29%)
HP:0025269	Panic attack	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Very rare (<1-4%)
HP:0002120	Cerebral cortical atrophy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 23
Mondo ID	MONDO:0013928
OMIM	614860
Orphanet	420492
DOID	DOID:0090051
UMLS	C3538999
MedGen	761274
GARD	0017694
Is cancer (heuristic)	no

Also known as: dystonia 23 · dystonia type 23 · DYT23

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › focal dystonia › dystonia 23

Related subtypes (11): anismus, cervical dystonia, focal hand dystonia, oculogyric crisis, spasmodic dystonia, craniofacial dystonia, X-linked dystonia-parkinsonism, torsion dystonia 7, benign essential blepharospasm, oromandibular dystonia, dystonia, focal, task-specific

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

7 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
189196	NM_000718.4(CACNA1B):c.4166G>A (p.Arg1389His)	CACNA1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029937	NM_000718.4(CACNA1B):c.3862G>A (p.Val1288Ile)	CACNA1B	Uncertain significance	criteria provided, single submitter
1032454	NM_000718.4(CACNA1B):c.2636C>A (p.Pro879His)	CACNA1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
522740	NM_000718.4(CACNA1B):c.5233A>G (p.Ser1745Gly)	CACNA1B	Uncertain significance	criteria provided, single submitter
638439	NM_000718.4(CACNA1B):c.4953C>A (p.Ser1651Arg)	CACNA1B	Uncertain significance	criteria provided, single submitter
2664743	NM_001131016.2(CIZ1):c.2023G>C (p.Asp675His)	CIZ1	Uncertain significance	criteria provided, single submitter
797749	NM_000718.4(CACNA1B):c.6840C>T (p.Phe2280=)	CACNA1B	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CIZ1	Moderate	Unknown	dystonia 23	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CIZ1	Orphanet:420492	Adult-onset cervical dystonia, DYT23 type
CACNA1B	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
CIZ1	HGNC:16744	ENSG00000148337	Q9ULV3	Cip1-interacting zinc finger protein	gencc,clinvar
CACNA1B	HGNC:1389	ENSG00000148408	Q00975	Voltage-dependent N-type calcium channel subunit alpha-1B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CIZ1	Cip1-interacting zinc finger protein	May regulate the subcellular localization of CIP/WAF1.
CACNA1B	Voltage-dependent N-type calcium channel subunit alpha-1B	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Ion channel	1	55.8×	0.036
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CIZ1	Transcription factor	no		Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type
CACNA1B	Ion channel	yes		EF_hand_dom, VDCCAlpha1, VDCC_N_a1su

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
cerebellar hemisphere	1
right hemisphere of cerebellum	1
right ovary	1
Brodmann (1909) area 23	1
middle temporal gyrus	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CIZ1	281	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, right ovary
CACNA1B	146	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CACNA1B	2,441
CIZ1	2,160

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CACNA1B	Q00975	7
CIZ1	Q9ULV3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Presynaptic depolarization and calcium channel opening	1	951.7×	0.003	CACNA1B
Transmission across Chemical Synapses	1	76.1×	0.020	CACNA1B
Neuronal System	1	44.3×	0.023	CACNA1B

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
positive regulation of DNA-templated DNA replication initiation	1	4213.0×	0.001	CIZ1
positive regulation of calcium ion-dependent exocytosis of neurotransmitter	1	2808.7×	0.001	CACNA1B
maintenance of protein location in nucleus	1	561.7×	0.003	CIZ1
response to amyloid-beta	1	495.6×	0.003	CACNA1B
random inactivation of X chromosome	1	468.1×	0.003	CIZ1
calcium ion import across plasma membrane	1	271.8×	0.005	CACNA1B
modulation of chemical synaptic transmission	1	91.6×	0.012	CACNA1B
chemical synaptic transmission	1	38.6×	0.026	CACNA1B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
CACNA1B	NIFEDIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1B	23	4
CIZ1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIFEDIPINE	4	CACNA1B
NIMODIPINE	4	CACNA1B
TACRINE	4	CACNA1B
IMIPRAMINE	4	CACNA1B
AMOXAPINE	4	CACNA1B
MAPROTILINE	4	CACNA1B
CLOMIPRAMINE	4	CACNA1B
NORTRIPTYLINE	4	CACNA1B
MIBEFRADIL	4	CACNA1B
ZICONOTIDE	4	CACNA1B
AMITRIPTYLINE	4	CACNA1B
PROMETHAZINE	4	CACNA1B
TRIMIPRAMINE	4	CACNA1B
PROTRIPTYLINE	4	CACNA1B
CYCLOBENZAPRINE	4	CACNA1B
DESIPRAMINE	4	CACNA1B
HESPERIDIN	3	CACNA1B
OPIPRAMOL	3	CACNA1B
CILNIDIPINE	3	CACNA1B
Z160	2	CACNA1B
SELICICLIB	2	CACNA1B
LOMERIZINE	2	CACNA1B
FLUNARIZINE	2	CACNA1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CACNA1B	135	Binding:110, Functional:25

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1B	135

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

23 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)
NIFEDIPINE	4	CACNA1B
NIMODIPINE	4	CACNA1B
TACRINE	4	CACNA1B
IMIPRAMINE	4	CACNA1B
AMOXAPINE	4	CACNA1B
MAPROTILINE	4	CACNA1B
CLOMIPRAMINE	4	CACNA1B
NORTRIPTYLINE	4	CACNA1B
MIBEFRADIL	4	CACNA1B
ZICONOTIDE	4	CACNA1B
AMITRIPTYLINE	4	CACNA1B
PROMETHAZINE	4	CACNA1B
TRIMIPRAMINE	4	CACNA1B
PROTRIPTYLINE	4	CACNA1B
CYCLOBENZAPRINE	4	CACNA1B
DESIPRAMINE	4	CACNA1B
HESPERIDIN	3	CACNA1B
OPIPRAMOL	3	CACNA1B
CILNIDIPINE	3	CACNA1B
Z160	2	CACNA1B
SELICICLIB	2	CACNA1B
LOMERIZINE	2	CACNA1B
FLUNARIZINE	2	CACNA1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CACNA1B
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	1	CIZ1

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)
CIZ1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.