Dystonia 30

Summary

Dystonia 30 (MONDO:0025691) is a disease caused by VPS16 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: VPS16 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 30
Mondo ID	MONDO:0025691
OMIM	619291
DOID	DOID:0060937
UMLS	C5543312
MedGen	1785079
GARD	0025479
Is cancer (heuristic)	no

Also known as: DYT30

Data availability: 30 ClinVar variants · 3 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 › dystonia 30

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 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

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

30 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 8 pathogenic, 8 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072036	NM_022575.4(VPS16):c.1955dup (p.Thr653fs)	PTPRA	Pathogenic	criteria provided, single submitter
987481	NM_022575.4(VPS16):c.1903C>T (p.Arg635Ter)	PTPRA	Pathogenic	criteria provided, multiple submitters, no conflicts
1065414	NM_022575.4(VPS16):c.1094_1095dup (p.Tyr366fs)	VPS16	Pathogenic	no assertion criteria provided
1065416	NM_022575.4(VPS16):c.1367+2T>C	VPS16	Pathogenic	no assertion criteria provided
1065417	NM_022575.4(VPS16):c.244_259delinsGAGAGC (p.Lys82fs)	VPS16	Pathogenic	no assertion criteria provided
1065418	NM_022575.4(VPS16):c.156C>A (p.Asn52Lys)	VPS16	Pathogenic	no assertion criteria provided
4813602	NM_022575.4(VPS16):c.539G>A (p.Trp180Ter)	VPS16	Pathogenic	criteria provided, single submitter
976681	NM_022575.4(VPS16):c.1335T>G (p.Tyr445Ter)	VPS16	Pathogenic	criteria provided, single submitter
1804074	NM_022575.4(VPS16):c.1988_1989insG (p.Asn663fs)	PTPRA	Likely pathogenic	criteria provided, single submitter
4072396	NM_022575.4(VPS16):c.2066dup (p.Gln690fs)	PTPRA	Likely pathogenic	criteria provided, single submitter
1347858	NM_022575.4(VPS16):c.1331+2T>C	VPS16	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1695013	NM_022575.4(VPS16):c.1389C>G (p.Tyr463Ter)	VPS16	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2663845	NM_022575.4(VPS16):c.143-2A>T	VPS16	Likely pathogenic	criteria provided, single submitter
4072035	NM_022575.4(VPS16):c.1818+2T>G	VPS16	Likely pathogenic	criteria provided, single submitter
4291133	NM_022575.4(VPS16):c.1513C>T (p.Arg505Ter)	VPS16	Likely pathogenic	criteria provided, single submitter
4531289	NM_022575.4(VPS16):c.1035dup (p.Gly346fs)	VPS16	Likely pathogenic	criteria provided, single submitter
1065413	NM_022575.4(VPS16):c.559C>T (p.Arg187Ter)	VPS16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1687303	NM_022575.4(VPS16):c.2005-10G>A	PTPRA	Uncertain significance	criteria provided, single submitter
4080999	NM_022575.4(VPS16):c.2454G>T (p.Thr818=)	PTPRA	Uncertain significance	criteria provided, single submitter
4279632	NM_022575.4(VPS16):c.2321A>G (p.Lys774Arg)	PTPRA	Uncertain significance	criteria provided, single submitter
4531750	NM_022575.4(VPS16):c.2004+1G>A	PTPRA	Uncertain significance	criteria provided, single submitter
1804162	NM_022575.4(VPS16):c.784C>T (p.Arg262Trp)	VPS16	Uncertain significance	criteria provided, multiple submitters, no conflicts
1879532	NM_022575.4(VPS16):c.1332-1G>T	VPS16	Uncertain significance	criteria provided, multiple submitters, no conflicts
2429767	NM_022575.4(VPS16):c.130G>A (p.Gly44Arg)	VPS16	Uncertain significance	criteria provided, single submitter
2438541	NM_022575.4(VPS16):c.1521del (p.Asn508fs)	VPS16	Uncertain significance	criteria provided, single submitter
2576548	NM_022575.4(VPS16):c.1614G>T (p.Leu538=)	VPS16	Uncertain significance	criteria provided, single submitter
3362381	NM_022575.4(VPS16):c.722G>A (p.Gly241Asp)	VPS16	Uncertain significance	criteria provided, single submitter
4080998	NM_022575.4(VPS16):c.995C>T (p.Ala332Val)	VPS16	Uncertain significance	criteria provided, single submitter
4081000	NM_022575.4(VPS16):c.715G>A (p.Asp239Asn)	VPS16	Uncertain significance	criteria provided, single submitter
4846960	NM_022575.4(VPS16):c.59_60del (p.Lys19_Tyr20insTer)	VPS16	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 0 · 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
VPS16	Strong	Autosomal dominant	dystonia 30	5

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
VPS16	HGNC:14584	ENSG00000215305	Q9H269	Vacuolar protein sorting-associated protein 16 homolog	gencc,clinvar
PTPRA	HGNC:9664	ENSG00000132670	P18433	Receptor-type tyrosine-protein phosphatase alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VPS16	Vacuolar protein sorting-associated protein 16 homolog	Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways.
PTPRA	Receptor-type tyrosine-protein phosphatase alpha	Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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
Phosphatase	1	42.0×	0.047
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VPS16	Other/Unknown	no		Vps16_C, Vps16_N, VPS16
PTPRA	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
granulocyte	1
right hemisphere of cerebellum	1
calcaneal tendon	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VPS16	275	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, cerebellar hemisphere
PTPRA	295	ubiquitous	marker	calcaneal tendon, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRA	1,920
VPS16	1,832

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VPS16	Q9H269	1
PTPRA	P18433	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 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	519.1×	0.006	VPS16
NCAM signaling for neurite out-growth	1	135.9×	0.011	PTPRA
RAF/MAP kinase cascade	1	30.5×	0.032	PTPRA

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
vacuole fusion, non-autophagic	1	2808.7×	0.004	VPS16
regulation of SNARE complex assembly	1	648.1×	0.006	VPS16
endosomal vesicle fusion	1	561.7×	0.006	VPS16
regulation of focal adhesion assembly	1	300.9×	0.008	PTPRA
autophagosome maturation	1	175.5×	0.010	VPS16
endosome to lysosome transport	1	168.5×	0.010	VPS16
endosomal transport	1	122.1×	0.012	VPS16
integrin-mediated signaling pathway	1	80.2×	0.016	PTPRA
intracellular protein transport	1	32.4×	0.034	VPS16
signal transduction	1	8.0×	0.121	PTPRA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VPS16	0	0
PTPRA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTPRA	41	Binding:41

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRA	3.1.3.48	protein-tyrosine-phosphatase

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

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	1	PTPRA
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	VPS16

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
VPS16	0	—
PTPRA	41	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.