Dystonia 32

Summary

Dystonia 32 (MONDO:0030486) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 32
Mondo ID	MONDO:0030486
OMIM	619637
DOID	DOID:0060939
UMLS	C5562029
MedGen	1794239
GARD	0025578
Is cancer (heuristic)	no

Also known as: DYT32

Data availability: 7 ClinVar variants.

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 › dystonia 32

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, combined dystonia, dystonia 30, dystonia 31, 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

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 benign, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1326862	NM_021729.6(VPS11):c.136C>T (p.Pro46Ser)	LOC130006887	Pathogenic	no assertion criteria provided
1305992	NM_021729.6(VPS11):c.1640G>A (p.Arg547His)	VPS11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1164301	NM_021729.6(VPS11):c.1266C>T (p.Tyr422=)	VPS11	Benign	criteria provided, multiple submitters, no conflicts
1165119	NM_021729.6(VPS11):c.1238+14C>T	VPS11	Benign	criteria provided, multiple submitters, no conflicts
1168494	NM_021729.6(VPS11):c.486C>G (p.Gly162=)	VPS11	Benign	criteria provided, multiple submitters, no conflicts
1684211	NM_021729.6(VPS11):c.1977C>T (p.Phe659=)	VPS11	Benign	criteria provided, single submitter
1684212	NM_021729.6(VPS11):c.*38A>G	VPS11	Benign	criteria provided, multiple submitters, no conflicts

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
VPS11	Orphanet:466934	VPS11-related autosomal recessive hypomyelinating leukodystrophy

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
VPS11	HGNC:14583	ENSG00000160695	Q9H270	Vacuolar protein sorting-associated protein 11 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VPS11	Vacuolar protein sorting-associated protein 11 homolog	Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways.

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)
VPS11	Transcription factor	no		Clathrin_H-chain/VPS_repeat, Znf_RING, TPR-like_helical_dom_sf

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
apex of heart	1
pituitary gland	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VPS11	134	ubiquitous	marker	prefrontal cortex, pituitary gland, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VPS11	1,773

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VPS11	Q9H270	79.01

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
SARS-CoV-2 modulates autophagy	1	1038.2×	1e-03	VPS11

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
organelle fusion	1	4213.0×	0.002	VPS11
regulation of organelle assembly	1	3370.4×	0.002	VPS11
positive regulation of early endosome to late endosome transport	1	1872.4×	0.002	VPS11
vacuole organization	1	1532.0×	0.002	VPS11
regulation of SNARE complex assembly	1	1296.3×	0.002	VPS11
negative regulation of intracellular estrogen receptor signaling pathway	1	1123.5×	0.002	VPS11
endosomal vesicle fusion	1	1123.5×	0.002	VPS11
obsolete vesicle docking involved in exocytosis	1	674.1×	0.003	VPS11
obsolete positive regulation of protein targeting to mitochondrion	1	495.6×	0.004	VPS11
endosome organization	1	374.5×	0.004	VPS11
endosome to lysosome transport	1	337.0×	0.004	VPS11
positive regulation of protein catabolic process	1	203.0×	0.007	VPS11
regulation of protein stability	1	125.8×	0.010	VPS11
autophagy	1	110.1×	0.010	VPS11
intracellular protein transport	1	64.8×	0.016	VPS11
protein ubiquitination	1	41.4×	0.024	VPS11

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
VPS11	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	VPS11

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)
VPS11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.