Epilepsy, progressive myoclonic, 12

Summary

Epilepsy, progressive myoclonic, 12 (MONDO:0030936) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, progressive myoclonic, 12
Mondo ID	MONDO:0030936
OMIM	619191
UMLS	C5543069
MedGen	1778162
GARD	0025665
Is cancer (heuristic)	no

Also known as: epilepsy, progressive myoclonic, 12 · EPM12

Data availability: 3 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, 12

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, epilepsy, progressive myoclonic, 1B, 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

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
973432	NM_032178.3(SLC7A6OS):c.191A>G (p.Gln64Arg)	PRMT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299431	NM_032178.3(SLC7A6OS):c.709T>C (p.Tyr237His)	SLC7A6OS	Uncertain significance	criteria provided, single submitter
3581221	NM_032178.3(SLC7A6OS):c.41A>T (p.Lys14Met)	SLC7A6OS	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
SLC7A6OS	Limited	Autosomal recessive	epilepsy	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRMT7	Orphanet:464288	Short stature-brachydactyly-obesity-global developmental delay syndrome

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
SLC7A6OS	HGNC:25807	ENSG00000103061	Q96CW6	Probable RNA polymerase II nuclear localization protein SLC7A6OS	gencc,clinvar
PRMT7	HGNC:25557	ENSG00000132600	Q9NVM4	Protein arginine N-methyltransferase 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC7A6OS	Probable RNA polymerase II nuclear localization protein SLC7A6OS	Directs RNA polymerase II nuclear import.
PRMT7	Protein arginine N-methyltransferase 7	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · 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
Enzyme (other)	1	6.0×	0.228
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC7A6OS	Transcription factor	no		TF_Iwr1_dom, SLC7A6OS
PRMT7	Enzyme (other)	yes	2.1.1.321	MeTrfase_PRMT7, Arg_MeTrfase, SAM-dependent_MTases_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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
pancreatic ductal cell	1
tendon of biceps brachii	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC7A6OS	224	ubiquitous	yes	pancreatic ductal cell, tendon of biceps brachii, apex of heart
PRMT7	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRMT7	2,036
SLC7A6OS	626

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRMT7	Q9NVM4	93.19
SLC7A6OS	Q96CW6	66.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
RMTs methylate histone arginines	1	146.4×	0.014	PRMT7
Chromatin organization	1	81.6×	0.014	PRMT7
Chromatin modifying enzymes	1	72.3×	0.014	PRMT7

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
peptidyl-arginine methylation	1	2106.5×	0.004	PRMT7
genomic imprinting	1	495.6×	0.007	PRMT7
developmental process	1	337.0×	0.007	SLC7A6OS
spliceosomal snRNP assembly	1	290.6×	0.007	PRMT7
hematopoietic progenitor cell differentiation	1	118.7×	0.013	SLC7A6OS
chromatin remodeling	1	36.5×	0.036	PRMT7
protein transport	1	21.9×	0.051	SLC7A6OS
regulation of DNA-templated transcription	1	15.8×	0.062	PRMT7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRMT7	1	3
SLC7A6OS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADEMETIONINE	3	PRMT7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRMT7	100	Binding:98, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRMT7	2.1.1.321	type III protein arginine methyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRMT7	100

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

1 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)
ADEMETIONINE	3	PRMT7

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	1	PRMT7
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SLC7A6OS

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)
SLC7A6OS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.