Dystonia 24

Summary

Dystonia 24 (MONDO:0014019) is a disease caused by ANO3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ANO3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 73
• Phenotypes (HPO): 9

Clinical features

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0000473	Torticollis	Frequent (30-79%)
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0002451	Limb dystonia	Frequent (30-79%)
HP:0012477	Vocal tremor	Frequent (30-79%)
HP:0007351	Upper limb postural tremor	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001600	Abnormality of the larynx	Occasional (5-29%)
HP:0002378	Hand tremor	Occasional (5-29%)
HP:0012048	Oromandibular dystonia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 24
Mondo ID	MONDO:0014019
OMIM	615034
Orphanet	420485
DOID	DOID:0090052
UMLS	C3554374
MedGen	767288
GARD	0017693
Is cancer (heuristic)	no

Also known as: ANO3 dystonic disorder · dystonia 24 · dystonia type 24 · dystonic disorder caused by mutation in ANO3 · DYT-ANO3 · DYT24

Data availability: 73 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › isolated dystonia › focal, segmental or multifocal dystonia › dystonia 24

Related subtypes (11): torsion dystonia 4, torsion dystonia 2, torsion dystonia 13, torsion dystonia 17, dystonia 23, dystonia 25, dystonia 27, oromandibular dystonia, blepharospasm-oromandibular dystonia syndrome, infantile-onset generalized dyskinesia with orofacial involvement, adult-onset segmental dystonia

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

73 retrieved; paginated sample, class counts are floors:

30 benign, 18 uncertain significance, 11 benign/likely benign, 5 conflicting classifications of pathogenicity, 4 pathogenic, 3 pathogenic/likely pathogenic, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
39496	NM_031418.4(ANO3):c.1480A>T (p.Arg494Trp)	ANO3	Pathogenic	no assertion criteria provided
39497	NM_031418.4(ANO3):c.1470G>T (p.Trp490Cys)	ANO3	Pathogenic	no assertion criteria provided
39498	NM_031418.4(ANO3):c.2053A>G (p.Ser685Gly)	ANO3	Pathogenic	no assertion criteria provided
39499	NM_031418.4(ANO3):c.2586G>T (p.Lys862Asn)	ANO3	Pathogenic	no assertion criteria provided
521283	NM_031418.4(ANO3):c.1819A>T (p.Ile607Phe)	ANO3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
641954	NM_031418.4(ANO3):c.1528G>A (p.Glu510Lys)	ANO3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
651774	NM_031418.4(ANO3):c.1943A>G (p.Asn648Ser)	ANO3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807374	NM_031418.4(ANO3):c.1969G>A (p.Ala657Thr)	ANO3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1700707	NM_031418.4(ANO3):c.1699G>A (p.Gly567Arg)	ANO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3362365	NM_001313726.2(ANO3):c.58C>T (p.His20Tyr)	ANO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
388790	NM_031418.4(ANO3):c.704A>G (p.Tyr235Cys)	ANO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412872	NM_031418.4(ANO3):c.164C>T (p.Ser55Phe)	ANO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
642181	NM_031418.4(ANO3):c.715G>A (p.Gly239Arg)	ANO3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007973	NM_031418.4(ANO3):c.2609C>T (p.Ser870Phe)	ANO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1696661	NM_031418.4(ANO3):c.702C>A (p.Cys234Ter)	ANO3	Uncertain significance	criteria provided, single submitter
1709837	NM_031418.4(ANO3):c.1714C>T (p.Arg572Cys)	ANO3	Uncertain significance	criteria provided, single submitter
1804916	NM_031418.4(ANO3):c.2306T>C (p.Val769Ala)	ANO3	Uncertain significance	criteria provided, single submitter
1986112	NM_031418.4(ANO3):c.1585C>A (p.Pro529Thr)	ANO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439108	NM_031418.4(ANO3):c.972del (p.Val325fs)	ANO3	Uncertain significance	criteria provided, single submitter
2439109	NM_031418.4(ANO3):c.160A>G (p.Thr54Ala)	ANO3	Uncertain significance	criteria provided, single submitter
2439110	NM_031418.4(ANO3):c.827C>G (p.Ser276Ter)	ANO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439111	NM_031418.4(ANO3):c.2858T>C (p.Val953Ala)	ANO3	Uncertain significance	criteria provided, single submitter
2584568	NM_031418.4(ANO3):c.944G>A (p.Arg315His)	ANO3	Uncertain significance	criteria provided, single submitter
3251964	NM_031418.4(ANO3):c.2090T>A (p.Val697Asp)	ANO3	Uncertain significance	criteria provided, single submitter
3376213	NM_031418.4(ANO3):c.2191G>A (p.Asp731Asn)	ANO3	Uncertain significance	criteria provided, single submitter
3381921	NM_001313726.2(ANO3):c.118C>T (p.Gln40Ter)	ANO3	Uncertain significance	criteria provided, single submitter
3779520	NM_031418.4(ANO3):c.269C>G (p.Ser90Cys)	ANO3	Uncertain significance	criteria provided, single submitter
3779522	NM_031418.4(ANO3):c.572G>A (p.Gly191Asp)	ANO3	Uncertain significance	criteria provided, single submitter
455986	NM_031418.4(ANO3):c.1807A>G (p.Asn603Asp)	ANO3	Uncertain significance	criteria provided, multiple submitters, no conflicts
575627	NM_031418.4(ANO3):c.743A>C (p.Gln248Pro)	ANO3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
ANO3	Strong	Autosomal dominant	dystonia 24	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANO3	Orphanet:420485	Cranio-cervical dystonia with laryngeal and upper-limb 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
ANO3	HGNC:14004	ENSG00000134343	Q9BYT9	Anoctamin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANO3	Anoctamin-3	Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANO3	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM

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
corpus epididymis	1
lateral globus pallidus	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANO3	189	broad	marker	corpus epididymis, lateral globus pallidus, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANO3	1,078

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO3	Q9BYT9	76.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Induction of Cell-Cell Fusion	1	878.5×	0.011	ANO3
Late SARS-CoV-2 Infection Events	1	292.8×	0.017	ANO3
Stimuli-sensing channels	1	135.9×	0.025	ANO3
Ion channel transport	1	96.0×	0.025	ANO3
SARS-CoV-2 Infection	1	80.4×	0.025	ANO3
SARS-CoV Infections	1	55.4×	0.030	ANO3
Viral Infection Pathways	1	30.8×	0.045	ANO3
Transport of small molecules	1	25.1×	0.045	ANO3
Infectious disease	1	24.8×	0.045	ANO3
Disease	1	13.1×	0.076	ANO3

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
detection of temperature stimulus	1	5617.3×	6e-04	ANO3
calcium activated galactosylceramide scrambling	1	5617.3×	6e-04	ANO3
calcium activated phosphatidylcholine scrambling	1	3370.4×	7e-04	ANO3
detection of mechanical stimulus	1	1203.7×	0.001	ANO3
chloride transmembrane transport	1	237.3×	0.006	ANO3
monoatomic ion transmembrane transport	1	208.1×	0.006	ANO3
establishment of localization in cell	1	160.5×	0.006	ANO3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ANO3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANO3

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)
ANO3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.