Oromandibular dystonia

Summary

Oromandibular dystonia (MONDO:0019771) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include levetiracetam.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 21
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000277	Abnormality of the mandible	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0001618	Dysphonia	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0005216	Impaired mastication	Frequent (30-79%)
HP:0010754	Abnormality of the temporomandibular joint	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0000159	Abnormal lip morphology	Occasional (5-29%)
HP:0000273	Facial grimacing	Occasional (5-29%)
HP:0000366	Abnormality of the nose	Occasional (5-29%)
HP:0000473	Torticollis	Occasional (5-29%)
HP:0000643	Blepharospasm	Occasional (5-29%)
HP:0002487	Hyperkinetic movements	Occasional (5-29%)
HP:0003763	Bruxism	Occasional (5-29%)
HP:0007325	Generalized dystonia	Occasional (5-29%)
HP:0012049	Laryngeal dystonia	Occasional (5-29%)
HP:0031008	Lingual dystonia	Occasional (5-29%)
HP:0001260	Dysarthria	Very rare (<1-4%)
HP:0002098	Respiratory distress	Very rare (<1-4%)
HP:0002451	Limb dystonia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oromandibular dystonia
Mondo ID	MONDO:0019771
Orphanet	93958
DOID	DOID:0050843
ICD-11	749381409
UMLS	C2242577
MedGen	473560
GARD	0019243
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

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 › oromandibular dystonia

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, dystonia 23, 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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
523307	NC_012920.1(MT-CO3):m.9355A>T	MT-CO3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-CO3	Orphanet:104	Leber hereditary optic neuropathy
MT-CO3	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO3	Orphanet:550	MELAS
MT-CO3	Orphanet:99845	Genetic recurrent myoglobinuria

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
MT-CO3	HGNC:7422	ENSG00000198938	P00414	Cytochrome c oxidase subunit 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MT-CO3	Cytochrome c oxidase subunit 3	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

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)
MT-CO3	Other/Unknown	no		Cyt_c_oxidase-like_su3, Cyt_c_oxidase_su3_a-hlx, Cyt_c/ubiquinol_Oxase_su3

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
endocervix	1
rectum	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-CO3	134	ubiquitous	marker	zone of skin, endocervix, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-CO3	1,791

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-CO3	P00414	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Complex IV assembly	1	228.4×	0.011	MT-CO3
Cytoprotection by HMOX1	1	184.2×	0.011	MT-CO3
TP53 Regulates Metabolic Genes	1	129.8×	0.011	MT-CO3
Mitochondrial translation termination	1	109.8×	0.011	MT-CO3
Respiratory electron transport	1	95.2×	0.011	MT-CO3

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
respiratory chain complex IV assembly	1	2407.4×	0.001	MT-CO3
mitochondrial electron transport, cytochrome c to oxygen	1	766.0×	0.002	MT-CO3
cellular respiration	1	432.1×	0.002	MT-CO3

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
MT-CO3	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
MT-CO3	1	Binding: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	0
E	Difficult family or no structure, no drug	1	MT-CO3

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)
MT-CO3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02199509	PHASE2	COMPLETED	Efficacy of Levetiracetam in Oromandibular and Cranial Dystonia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEVETIRACETAM	4	1