Progressive myoclonic epilepsy with dystonia

Summary

Progressive myoclonic epilepsy with dystonia (MONDO:0018126) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001332	Dystonia	Very frequent (80-99%)
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0002788	Recurrent upper respiratory tract infections	Very frequent (80-99%)
HP:0007256	Abnormal pyramidal sign	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0001326	EEG with irregular generalized spike and wave complexes	Frequent (30-79%)
HP:0002123	Generalized myoclonic seizure	Frequent (30-79%)
HP:0002133	Status epilepticus	Frequent (30-79%)
HP:0002188	Delayed CNS myelination	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0008935	Generalized neonatal hypotonia	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0200134	Epileptic encephalopathy	Frequent (30-79%)
HP:0001262	Excessive daytime somnolence	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001269	Hemiparesis	Occasional (5-29%)
HP:0002071	Abnormality of extrapyramidal motor function	Occasional (5-29%)
HP:0002301	Hemiplegia	Occasional (5-29%)
HP:0002506	Diffuse cerebral atrophy	Occasional (5-29%)
HP:0025152	Poor visual behavior for age	Occasional (5-29%)
HP:0100275	Diffuse cerebellar atrophy	Occasional (5-29%)
HP:0000648	Optic atrophy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive myoclonic epilepsy with dystonia
Mondo ID	MONDO:0018126
Orphanet	352596
SNOMED CT	763349002
UMLS	C4706413
MedGen	1642042
GARD	0017522
Is cancer (heuristic)	no

Also known as: PMED · progressive myoclonus epilepsy with dystonia

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › infantile epilepsy syndrome › progressive myoclonic epilepsy with dystonia

Related subtypes (8): intellectual disability, autosomal dominant 5, benign partial infantile seizures, infant epilepsy with migrant focal crisis, infantile spasms-broad thumbs syndrome, infantile-onset mesial temporal lobe epilepsy with severe cognitive regression, undetermined early-onset epileptic encephalopathy, idiopathic hemiconvulsion-hemiplegia syndrome, myoclonic epilepsy in infancy

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 8 · 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
TBC1D24	Definitive	Autosomal recessive	familial infantile myoclonic epilepsy	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBC1D24	Orphanet:163727	Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome
TBC1D24	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
TBC1D24	Orphanet:352582	Familial infantile myoclonic epilepsy
TBC1D24	Orphanet:352587	Focal epilepsy-intellectual disability-cerebro-cerebellar malformation
TBC1D24	Orphanet:352596	Progressive myoclonic epilepsy with dystonia
TBC1D24	Orphanet:79500	DOORS syndrome
TBC1D24	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TBC1D24	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
TBC1D24	HGNC:29203	ENSG00000162065	Q9ULP9	TBC1 domain family member 24	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D24	TBC1 domain family member 24	May act as a GTPase-activating protein for Rab family protein(s).

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)
TBC1D24	Other/Unknown	no		Rab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_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
Brodmann (1909) area 23	1
middle temporal gyrus	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D24	227	ubiquitous	marker	parotid gland, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBC1D24	1,016

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D24	Q9ULP9	84.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Rab regulation of trafficking	1	368.4×	0.008	TBC1D24
TBC/RABGAPs	1	259.6×	0.008	TBC1D24
Membrane Trafficking	1	37.1×	0.029	TBC1D24
Vesicle-mediated transport	1	34.8×	0.029	TBC1D24

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
negative regulation of cellular response to oxidative stress	1	4213.0×	0.002	TBC1D24
positive regulation of neuron migration	1	991.3×	0.003	TBC1D24
positive regulation of dendrite morphogenesis	1	887.0×	0.003	TBC1D24
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	TBC1D24
axon development	1	455.5×	0.003	TBC1D24
synaptic vesicle endocytosis	1	432.1×	0.003	TBC1D24
dendrite development	1	391.9×	0.003	TBC1D24
cellular response to oxidative stress	1	154.6×	0.007	TBC1D24
neuron projection development	1	122.1×	0.008	TBC1D24

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
TBC1D24	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	TBC1D24

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)
TBC1D24	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.