Myoclonic dystonia 11

Summary

Myoclonic dystonia 11 (MONDO:0008044) is a disease caused by SGCE (GenCC Definitive), with 4 cohort genes and 1 clinical trial.

At a glance

• Causal gene: SGCE (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 636
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonic dystonia 11
Mondo ID	MONDO:0008044
OMIM	159900
DOID	DOID:0090034
UMLS	C1834570
MedGen	331778
GARD	0018616
Is cancer (heuristic)	no

Also known as: alcohol-responsive dystonia · dystonia 11, myoclonic · dystonia-11, myoclonic · DYT11 · myoclonic dystonia 11 · myoclonic dystonia type 11 · myoclonus-dystonia syndrome caused by mutation in SGCE · SGCE myoclonus-dystonia syndrome

Data availability: 636 ClinVar variants · 5 GenCC gene-disease records · 6 cell lines.

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 › combined dystonia › myoclonus-dystonia syndrome › myoclonic dystonia 11

Related subtypes (2): myoclonic dystonia 15, myoclonic dystonia 26

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

600 retrieved; paginated sample, class counts are floors:

267 uncertain significance, 156 likely benign, 112 pathogenic, 18 conflicting classifications of pathogenicity, 18 likely pathogenic, 13 pathogenic/likely pathogenic, 9 benign/likely benign, 7 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065199	NM_003919.3(SGCE):c.1011del (p.Ala336_Tyr337insTer)	CASD1	Pathogenic	no assertion criteria provided
1069378	NM_003919.3(SGCE):c.942C>A (p.Tyr314Ter)	CASD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070683	NM_003919.3(SGCE):c.623_650del (p.Gly208fs)	CASD1	Pathogenic	criteria provided, single submitter
1074768	NM_003919.3(SGCE):c.604dup (p.Thr202fs)	CASD1	Pathogenic	criteria provided, single submitter
1172914	NM_003919.3(SGCE):c.662G>T (p.Gly221Val)	CASD1	Pathogenic	no assertion criteria provided
1213596	NM_003919.3(SGCE):c.850del (p.Thr284fs)	CASD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1321115	NM_003919.3(SGCE):c.751G>T (p.Glu251Ter)	CASD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1323588	NM_003919.3(SGCE):c.1296dup (p.Gly433fs)	CASD1	Pathogenic	criteria provided, single submitter
1325061	NM_003919.3(SGCE):c.802dup (p.Ile268fs)	CASD1	Pathogenic	criteria provided, single submitter
1329499	NM_003919.3(SGCE):c.521del (p.Met174fs)	CASD1	Pathogenic	criteria provided, single submitter
1342071	NM_003919.3(SGCE):c.391-1G>A	CASD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1351337	NM_003919.3(SGCE):c.321del (p.Pro108fs)	CASD1	Pathogenic	criteria provided, single submitter
1403187	NM_003919.3(SGCE):c.865_866insGCAGGAAGTGA (p.Ile289delinsSerArgLysTer)	CASD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404117	NM_003919.3(SGCE):c.153C>G (p.Tyr51Ter)	CASD1	Pathogenic	criteria provided, single submitter
1420908	NM_003919.3(SGCE):c.193_194del (p.Glu65fs)	CASD1	Pathogenic	criteria provided, single submitter
1426795	NM_003919.3(SGCE):c.463+2T>A	CASD1	Pathogenic	criteria provided, single submitter
1429282	NM_003919.3(SGCE):c.942C>G (p.Tyr314Ter)	CASD1	Pathogenic	criteria provided, single submitter
1440019	NM_003919.3(SGCE):c.580del (p.Glu194fs)	CASD1	Pathogenic	criteria provided, single submitter
1442309	NM_003919.3(SGCE):c.704_707del (p.Cys235fs)	CASD1	Pathogenic	criteria provided, single submitter
1446049	NM_003919.3(SGCE):c.895G>T (p.Gly299Ter)	CASD1	Pathogenic	criteria provided, single submitter
1449245	NM_003919.3(SGCE):c.904_908dup (p.Pro304fs)	CASD1	Pathogenic	criteria provided, single submitter
1451374	NM_003919.3(SGCE):c.903C>A (p.Tyr301Ter)	CASD1	Pathogenic	criteria provided, single submitter
1451375	NM_003919.3(SGCE):c.448_452del (p.Ile150fs)	CASD1	Pathogenic	criteria provided, single submitter
1451845	NM_003919.3(SGCE):c.813C>A (p.Cys271Ter)	CASD1	Pathogenic	criteria provided, single submitter
1452174	NM_003919.3(SGCE):c.495_498del (p.Phe165fs)	CASD1	Pathogenic	criteria provided, single submitter
1454062	NM_003919.3(SGCE):c.663-2A>T	CASD1	Pathogenic	criteria provided, single submitter
1454373	NM_003919.3(SGCE):c.571_572del (p.Trp191fs)	CASD1	Pathogenic	criteria provided, single submitter
1454493	NM_003919.3(SGCE):c.344A>G (p.Tyr115Cys)	CASD1	Pathogenic	criteria provided, single submitter
1456373	NM_003919.3(SGCE):c.191_197dup (p.Tyr66Ter)	CASD1	Pathogenic	criteria provided, single submitter
1459921	NM_003919.3(SGCE):c.658del (p.Glu220fs)	CASD1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
SGCE	Definitive	Autosomal dominant	myoclonic dystonia 11	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCE	Orphanet:36899	Myoclonus-dystonia syndrome
DRD2	Orphanet:36899	Myoclonus-dystonia syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGCE	HGNC:10808	ENSG00000127990	O43556	Epsilon-sarcoglycan	gencc,clinvar
ASB4	HGNC:16009	ENSG00000005981	Q9Y574	Ankyrin repeat and SOCS box protein 4	clinvar
CASD1	HGNC:16014	ENSG00000127995	Q96PB1	N-acetylneuraminate (7)9-O-acetyltransferase	clinvar
DRD2	HGNC:3023	ENSG00000149295	P14416	D(2) dopamine receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCE	Epsilon-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
ASB4	Ankyrin repeat and SOCS box protein 4	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CASD1	N-acetylneuraminate (7)9-O-acetyltransferase	Key enzyme in the biosynthesis of O-acetylated (O-Ac) sialoglycans such as gangliosides O-AcGD3 and O-AcGD2, which affect various processes such as cell-cell interactions, host-pathogen recognition.
DRD2	D(2) dopamine receptor	Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

Protein-family classification

Druggable: 2 · Difficult: 1 · 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
GPCR	1	6.0×	0.392
Scaffold/PPI	1	4.3×	0.392
Enzyme (other)	1	3.0×	0.392
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGCE	Other/Unknown	no		Cadg, Sarcoglycan_alpha/epsilon, Sarcoglycan_N
ASB4	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
CASD1	Enzyme (other)	yes	2.3.1.45	Cas1_AcylTrans_dom, Cyclin-like_sf, NXPE4_C
DRD2	GPCR	yes		GPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D2_rcpt

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	2
left ovary	1
right ovary	1
tendon of biceps brachii	1
right adrenal gland	1
right adrenal gland cortex	1
Ammon’s horn	1
postcentral gyrus	1
male germ line stem cell (sensu Vertebrata) in testis	1
nucleus accumbens	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGCE	289	ubiquitous	marker	tendon of biceps brachii, left ovary, right ovary
ASB4	168	tissue_specific	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
CASD1	278	ubiquitous	marker	adrenal tissue, postcentral gyrus, Ammon’s horn
DRD2	159	broad	yes	putamen, nucleus accumbens, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRD2	3,148
ASB4	1,645
SGCE	909
CASD1	426

Intra-cohort edges

A	B	Sources
ASB4	CASD1	string_interaction
ASB4	SGCE	string_interaction
CASD1	SGCE	string_interaction
DRD2	SGCE	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DRD2	P14416	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASB4	Q9Y574	92.69
CASD1	Q96PB1	87.87
SGCE	O43556	74.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dopamine receptors	1	761.3×	0.014	DRD2
Formation of the dystrophin-glycoprotein complex (DGC)	1	102.9×	0.053	SGCE
Non-integrin membrane-ECM interactions	1	51.4×	0.071	SGCE
Class I MHC mediated antigen processing & presentation	1	23.4×	0.103	ASB4
Extracellular matrix organization	1	21.0×	0.103	SGCE
Neddylation	1	15.8×	0.114	ASB4
Antigen processing: Ubiquitination & Proteasome degradation	1	12.4×	0.123	ASB4
Adaptive Immune System	1	9.9×	0.134	ASB4
Post-translational protein modification	1	6.4×	0.181	ASB4
Immune System	1	4.3×	0.223	ASB4
Metabolism of proteins	1	4.1×	0.223	ASB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of circadian sleep/wake cycle, sleep	1	4213.0×	0.007	DRD2
orbitofrontal cortex development	1	2106.5×	0.007	DRD2
regulation of locomotion involved in locomotory behavior	1	2106.5×	0.007	DRD2
positive regulation of glial cell-derived neurotrophic factor production	1	2106.5×	0.007	DRD2
nervous system process involved in regulation of systemic arterial blood pressure	1	1404.3×	0.007	DRD2
response to inactivity	1	1404.3×	0.007	DRD2
acid secretion	1	1404.3×	0.007	DRD2
positive regulation of dopamine uptake involved in synaptic transmission	1	1404.3×	0.007	DRD2
negative regulation of dopamine receptor signaling pathway	1	1404.3×	0.007	DRD2
negative regulation of dopamine secretion	1	1053.2×	0.007	DRD2
response to histamine	1	1053.2×	0.007	DRD2
negative regulation of dephosphorylation	1	1053.2×	0.007	DRD2
positive regulation of renal sodium excretion	1	1053.2×	0.007	DRD2
regulation of synapse structural plasticity	1	1053.2×	0.007	DRD2
negative regulation of cellular response to hypoxia	1	1053.2×	0.007	DRD2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	842.6×	0.007	DRD2
beta-arrestin-dependent dopamine receptor signaling pathway	1	842.6×	0.007	DRD2
cerebral cortex GABAergic interneuron migration	1	702.2×	0.008	DRD2
auditory behavior	1	702.2×	0.008	DRD2
adenohypophysis development	1	601.9×	0.008	DRD2
branching morphogenesis of a nerve	1	601.9×	0.008	DRD2
regulation of dopamine uptake involved in synaptic transmission	1	601.9×	0.008	DRD2
hyaloid vascular plexus regression	1	601.9×	0.008	DRD2
phospholipase C-activating dopamine receptor signaling pathway	1	526.6×	0.008	DRD2
regulation of potassium ion transport	1	468.1×	0.008	DRD2
dopamine uptake involved in synaptic transmission	1	468.1×	0.008	DRD2
positive regulation of growth hormone secretion	1	468.1×	0.008	DRD2
G protein-coupled receptor internalization	1	421.3×	0.008	DRD2
neuron-neuron synaptic transmission	1	421.3×	0.008	DRD2
negative regulation of synaptic transmission, glutamatergic	1	421.3×	0.008	DRD2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
DRD2	CABERGOLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRD2	298	4
SGCE	0	0
ASB4	0	0
CASD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABERGOLINE	4	DRD2
APOMORPHINE	4	DRD2
HALOPERIDOL	4	DRD2
ROPINIROLE	4	DRD2
DOPAMINE	4	DRD2
BEPRIDIL	4	DRD2
CLOTRIMAZOLE	4	DRD2
METHYSERGIDE	4	DRD2
OXAPROZIN	4	DRD2
ACETOPHENAZINE	4	DRD2
IMIPRAMINE	4	DRD2
DROPERIDOL	4	DRD2
ARIPIPRAZOLE	4	DRD2
AMOXAPINE	4	DRD2
IDARUBICIN	4	DRD2
SAQUINAVIR	4	DRD2
PONATINIB	4	DRD2
DESLORATADINE	4	DRD2
DULOXETINE	4	DRD2
BETAMETHASONE DIPROPIONATE	4	DRD2
TIOCONAZOLE	4	DRD2
NEFAZODONE HYDROCHLORIDE	4	DRD2
DIHYDROERGOTAMINE MESYLATE	4	DRD2
FEXOFENADINE HYDROCHLORIDE	4	DRD2
AZELASTINE HYDROCHLORIDE	4	DRD2
HALOPERIDOL DECANOATE	4	DRD2
THIOTHIXENE	4	DRD2
ARMODAFINIL	4	DRD2
BENZTROPINE	4	DRD2
PROPIOMAZINE	4	DRD2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DRD2	2,636	Binding:2064, Functional:517, ADMET:54, Unclassified:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CASD1	2.3.1.45	N-acetylneuraminate 9-O-acetyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DRD2	2,636

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
CABERGOLINE	4	DRD2
APOMORPHINE	4	DRD2
HALOPERIDOL	4	DRD2
ROPINIROLE	4	DRD2
DOPAMINE	4	DRD2
BEPRIDIL	4	DRD2
CLOTRIMAZOLE	4	DRD2
METHYSERGIDE	4	DRD2
OXAPROZIN	4	DRD2
ACETOPHENAZINE	4	DRD2
IMIPRAMINE	4	DRD2
DROPERIDOL	4	DRD2
ARIPIPRAZOLE	4	DRD2
AMOXAPINE	4	DRD2
IDARUBICIN	4	DRD2
SAQUINAVIR	4	DRD2
PONATINIB	4	DRD2
DESLORATADINE	4	DRD2
DULOXETINE	4	DRD2
BETAMETHASONE DIPROPIONATE	4	DRD2
TIOCONAZOLE	4	DRD2
NEFAZODONE HYDROCHLORIDE	4	DRD2
DIHYDROERGOTAMINE MESYLATE	4	DRD2
FEXOFENADINE HYDROCHLORIDE	4	DRD2
AZELASTINE HYDROCHLORIDE	4	DRD2
HALOPERIDOL DECANOATE	4	DRD2
THIOTHIXENE	4	DRD2
ARMODAFINIL	4	DRD2
BENZTROPINE	4	DRD2
PROPIOMAZINE	4	DRD2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DRD2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CASD1
E	Difficult family or no structure, no drug	2	SGCE, ASB4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SGCE	0	—
ASB4	0	—
CASD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05671068	Not specified	COMPLETED	EMOTION & COGNITION IN MYOCLONUS DYSTONIA (AGENT10-ECODYST)