Dystonia 31

Summary

Dystonia 31 (MONDO:0030455) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 31
Mondo ID	MONDO:0030455
OMIM	619565
DOID	DOID:0060938
UMLS	C5562001
MedGen	1794211
GARD	0025566
Is cancer (heuristic)	no

Also known as: DYT31

Data availability: 11 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 31

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 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

11 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 4 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1319959	NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter)	AOPEP	Pathogenic	criteria provided, single submitter
1319960	NM_001193329.3(AOPEP):c.777G>A (p.Trp259Ter)	AOPEP	Pathogenic	no assertion criteria provided
1319963	NM_001193329.3(AOPEP):c.1744del (p.Met582fs)	AOPEP	Pathogenic	criteria provided, single submitter
2663844	NM_001193329.3(AOPEP):c.964+2T>G	AOPEP	Pathogenic	criteria provided, single submitter
1319961	NM_001193329.3(AOPEP):c.763C>T (p.Arg255Ter)	AOPEP	Likely pathogenic	criteria provided, single submitter
1319962	NM_001193329.3(AOPEP):c.1215del (p.Val406fs)	AOPEP	Likely pathogenic	criteria provided, single submitter
2498245	NM_001193329.3(AOPEP):c.703C>T (p.Gln235Ter)	AOPEP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3391298	NM_001193329.3(AOPEP):c.219del (p.Lys73fs)	AOPEP	Likely pathogenic	criteria provided, single submitter
3779335	NM_001193329.3(AOPEP):c.2207dup (p.Tyr736Ter)	AOPEP	Likely pathogenic	criteria provided, single submitter
3779336	NM_001193329.3(AOPEP):c.1134_1135del (p.Cys378fs)	AOPEP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4057234	NM_001193329.3(AOPEP):c.1201C>T (p.Arg401Trp)	AOPEP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold

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
ascending aorta	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AOPEP	991

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AOPEP	Q8N6M6	83.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
proteolysis	1	34.2×	0.029	AOPEP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AOPEP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
AOPEP	1	ADMET:1

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	1	AOPEP
E	Difficult family or no structure, no drug	0

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)
AOPEP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.