epilepsy, progressive myoclonic, 1B

Summary

epilepsy, progressive myoclonic, 1B (MONDO:0012904) is a disease caused by PRICKLE1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PRICKLE1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 506

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, progressive myoclonic, 1B
Mondo ID	MONDO:0012904
MeSH	C580388
OMIM	612437
DOID	DOID:0111448
SNOMED CT	702326000
UMLS	C2676254
MedGen	394003
GARD	0015556
Is cancer (heuristic)	no

Also known as: epilepsy, progressive myoclonic 1B · epilepsy, progressive myoclonic, 1B · epilepsy, progressive myoclonic, type 1B · EPM1B · PRICKLE1 progressive myoclonic epilepsy · progressive myoclonic epilepsy caused by mutation in PRICKLE1

Data availability: 506 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › progressive myoclonus epilepsy › epilepsy, progressive myoclonic, 1B

Related subtypes (14): Lafora disease, Unverricht-Lundborg syndrome, action myoclonus-renal failure syndrome, MERRF syndrome, familial encephalopathy with neuroserpin inclusion bodies, neuronal ceroid lipofuscinosis 8 northern epilepsy variant, progressive myoclonic epilepsy type 3, progressive myoclonic epilepsy type 6, progressive myoclonic epilepsy type 7, progressive myoclonic epilepsy type 8, progressive myoclonic epilepsy type 9, early-onset Lafora body disease, epilepsy, progressive myoclonic, 11, epilepsy, progressive myoclonic, 12

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

506 retrieved; paginated sample, class counts are floors:

301 uncertain significance, 168 likely benign, 14 conflicting classifications of pathogenicity, 13 benign/likely benign, 7 benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2283	NM_153026.3(PRICKLE1):c.311G>A (p.Arg104Gln)	LOC130007700	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30730	NM_153026.3(PRICKLE1):c.1414T>C (p.Tyr472His)	PRICKLE1	Pathogenic	no assertion criteria provided
243056	Single allele	LOC130007705	Likely pathogenic	criteria provided, single submitter
198620	NM_153026.3(PRICKLE1):c.1248G>A (p.Thr416=)	LOC126861509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130025	NM_153026.3(PRICKLE1):c.2071A>G (p.Thr691Ala)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
138808	NM_153026.3(PRICKLE1):c.1461C>T (p.Ser487=)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167530	NM_153026.3(PRICKLE1):c.2262C>G (p.Leu754=)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198918	NM_153026.3(PRICKLE1):c.2216C>T (p.Ser739Phe)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206653	NM_153026.3(PRICKLE1):c.1639+3A>G	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206654	NM_153026.3(PRICKLE1):c.1985A>G (p.Asn662Ser)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206656	NM_153026.3(PRICKLE1):c.2404C>T (p.Pro802Ser)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206658	NM_153026.3(PRICKLE1):c.113C>T (p.Pro38Leu)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206667	NM_153026.3(PRICKLE1):c.1360G>A (p.Glu454Lys)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206676	NM_153026.3(PRICKLE1):c.1888C>G (p.Gln630Glu)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
308708	NM_153026.3(PRICKLE1):c.435G>A (p.Ala145=)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96505	NM_153026.3(PRICKLE1):c.114G>A (p.Pro38=)	PRICKLE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183157	NM_001199107.2(TBC1D24):c.1079G>T (p.Arg360Leu)	TBC1D24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002582	NM_153026.3(PRICKLE1):c.1240T>C (p.Tyr414His)	LOC126861509	Uncertain significance	criteria provided, single submitter
1006994	NM_153026.3(PRICKLE1):c.949dup (p.Ser317fs)	LOC126861509	Uncertain significance	criteria provided, single submitter
1025395	NM_153026.3(PRICKLE1):c.1208A>G (p.Glu403Gly)	LOC126861509	Uncertain significance	criteria provided, single submitter
1046392	NM_153026.3(PRICKLE1):c.1103A>G (p.Asp368Gly)	LOC126861509	Uncertain significance	criteria provided, single submitter
1059366	NM_153026.3(PRICKLE1):c.1012A>G (p.Lys338Glu)	LOC126861509	Uncertain significance	criteria provided, multiple submitters, no conflicts
1325519	NM_153026.3(PRICKLE1):c.910A>C (p.Lys304Gln)	LOC126861509	Uncertain significance	criteria provided, multiple submitters, no conflicts
1353024	NM_153026.3(PRICKLE1):c.987C>G (p.Asp329Glu)	LOC126861509	Uncertain significance	criteria provided, single submitter
1357954	NM_153026.3(PRICKLE1):c.857C>A (p.Ala286Asp)	LOC126861509	Uncertain significance	criteria provided, single submitter
1376932	NM_153026.3(PRICKLE1):c.820G>C (p.Ala274Pro)	LOC126861509	Uncertain significance	criteria provided, multiple submitters, no conflicts
1395713	NM_153026.3(PRICKLE1):c.1124T>C (p.Leu375Ser)	LOC126861509	Uncertain significance	criteria provided, single submitter
1407056	NM_153026.3(PRICKLE1):c.1219G>A (p.Glu407Lys)	LOC126861509	Uncertain significance	criteria provided, single submitter
1416382	NM_153026.3(PRICKLE1):c.778G>A (p.Val260Met)	LOC126861509	Uncertain significance	criteria provided, single submitter
1428491	NM_153026.3(PRICKLE1):c.986A>G (p.Asp329Gly)	LOC126861509	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 9 · 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
PRICKLE1	Strong	Autosomal recessive	epilepsy, progressive myoclonic, 1B	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRICKLE1	Orphanet:308	Progressive myoclonic epilepsy type 1
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRICKLE1	HGNC:17019	ENSG00000139174	Q96MT3	Prickle-like protein 1	gencc,clinvar
TBC1D24	HGNC:29203	ENSG00000162065	Q9ULP9	TBC1 domain family member 24	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRICKLE1	Prickle-like protein 1	Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.
TBC1D24	TBC1 domain family member 24	May act as a GTPase-activating protein for Rab family protein(s).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRICKLE1	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
TBC1D24	Other/Unknown	no		Rab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_sf

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
buccal mucosa cell	1
lateral nuclear group of thalamus	1
tendon of biceps brachii	1
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
PRICKLE1	243	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral nuclear group of thalamus
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
PRICKLE1	1,485
TBC1D24	1,016

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D24	Q9ULP9	84.46
PRICKLE1	Q96MT3	55.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Rab regulation of trafficking	1	184.2×	0.016	TBC1D24
TBC/RABGAPs	1	129.8×	0.016	TBC1D24
Asymmetric localization of PCP proteins	1	102.0×	0.016	PRICKLE1
Membrane Trafficking	1	18.5×	0.057	TBC1D24
Vesicle-mediated transport	1	17.4×	0.057	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dendrite development	2	391.9×	3e-04	PRICKLE1, TBC1D24
polarized secretion of basement membrane proteins in epithelium	1	4213.0×	0.003	PRICKLE1
anterior visceral endoderm cell migration	1	4213.0×	0.003	PRICKLE1
negative regulation of cardiac muscle cell myoblast differentiation	1	4213.0×	0.003	PRICKLE1
establishment of bipolar cell polarity involved in cell morphogenesis	1	2808.7×	0.003	PRICKLE1
focal adhesion disassembly	1	2808.7×	0.003	PRICKLE1
renal tubule development	1	2106.5×	0.003	PRICKLE1
tear secretion	1	2106.5×	0.003	PRICKLE1
maintenance of postsynaptic density structure	1	2106.5×	0.003	PRICKLE1
negative regulation of cellular response to oxidative stress	1	2106.5×	0.003	TBC1D24
embryonic nail plate morphogenesis	1	1685.2×	0.003	PRICKLE1
mesenchyme development	1	1203.7×	0.004	PRICKLE1
primitive streak formation	1	702.2×	0.006	PRICKLE1
cornea development in camera-type eye	1	648.1×	0.006	PRICKLE1
eyelid development in camera-type eye	1	526.6×	0.006	PRICKLE1
positive regulation of neuron migration	1	495.6×	0.006	TBC1D24
cytoskeleton-dependent intracellular transport	1	468.1×	0.006	PRICKLE1
extracellular matrix assembly	1	468.1×	0.006	PRICKLE1
positive regulation of dendrite morphogenesis	1	443.5×	0.006	TBC1D24
regulation of postsynaptic density assembly	1	443.5×	0.006	PRICKLE1
embryonic brain development	1	401.2×	0.006	PRICKLE1
post-anal tail morphogenesis	1	366.4×	0.007	PRICKLE1
response to electrical stimulus	1	324.1×	0.007	PRICKLE1
cardiac muscle cell development	1	312.1×	0.007	PRICKLE1
coronary vasculature development	1	312.1×	0.007	PRICKLE1
tissue homeostasis	1	280.9×	0.007	PRICKLE1
aorta development	1	280.9×	0.007	PRICKLE1
neuron projection extension	1	263.3×	0.007	PRICKLE1
positive regulation of excitatory postsynaptic potential	1	263.3×	0.007	TBC1D24
basement membrane organization	1	255.3×	0.007	PRICKLE1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
PRICKLE1	0	0
TBC1D24	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PRICKLE1, TBC1D24

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)
PRICKLE1	0	—
TBC1D24	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.