myoclonic epilepsy of Lafora 2

Summary

myoclonic epilepsy of Lafora 2 (MONDO:0800306) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonic epilepsy of Lafora 2
Mondo ID	MONDO:0800306
OMIM	620681
DOID	DOID:0061211
UMLS	C1850764
MedGen	340621
GARD	0026491
Is cancer (heuristic)	no

Also known as: epilepsy, progressive myoclonic, 2B · EPM2B · Lafora disease 2 · MELF2 · myoclonic epilepsy of Lafora 2

Data availability: 17 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › Lafora disease › myoclonic epilepsy of Lafora 2

Related subtypes (1): myoclonic epilepsy of Lafora 1

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

17 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 uncertain significance, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
162618	NM_198586.3(NHLRC1):c.436G>A (p.Asp146Asn)	NHLRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206187	NM_198586.3(NHLRC1):c.386C>A (p.Pro129His)	NHLRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2586	NM_198586.3(NHLRC1):c.76T>A (p.Cys26Ser)	NHLRC1	Pathogenic	criteria provided, single submitter
2587	NM_198586.3(NHLRC1):c.205C>G (p.Pro69Ala)	NHLRC1	Pathogenic	criteria provided, multiple submitters, no conflicts
2588	NM_198586.3(NHLRC1):c.468_469del (p.Gly158fs)	NHLRC1	Pathogenic	criteria provided, multiple submitters, no conflicts
2589	NM_198586.3(NHLRC1):c.992del (p.Gly331fs)	NHLRC1	Pathogenic	criteria provided, single submitter
2590	NM_198586.3(NHLRC1):c.793C>T (p.Arg265Ter)	NHLRC1	Pathogenic	no assertion criteria provided
2592	NM_198586.3(NHLRC1):c.923A>C (p.Asp308Ala)	NHLRC1	Pathogenic	no assertion criteria provided
933637	NM_198586.3(NHLRC1):c.361G>A (p.Gly121Ser)	NHLRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2591	NM_198586.3(NHLRC1):c.593T>A (p.Ile198Asn)	NHLRC1	Likely pathogenic	criteria provided, single submitter
4279605	NM_198586.3(NHLRC1):c.488_542del (p.Gln163fs)	NHLRC1	Likely pathogenic	criteria provided, single submitter
167350	NM_198586.3(NHLRC1):c.32C>A (p.Ala11Glu)	NHLRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193518	NM_198586.3(NHLRC1):c.46A>G (p.Met16Val)	NHLRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013606	NM_198586.3(NHLRC1):c.254C>G (p.Pro85Arg)	NHLRC1	Uncertain significance	criteria provided, single submitter
3891834	NM_198586.3(NHLRC1):c.55G>T (p.Ala19Ser)	NHLRC1	Uncertain significance	criteria provided, single submitter
3891835	NM_198586.3(NHLRC1):c.56C>T (p.Ala19Val)	NHLRC1	Uncertain significance	criteria provided, single submitter
977342	NM_198586.3(NHLRC1):c.721C>G (p.Leu241Val)	NHLRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NHLRC1	Orphanet:501	Lafora disease

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
NHLRC1	HGNC:21576	ENSG00000187566	Q6VVB1	E3 ubiquitin-protein ligase NHLRC1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NHLRC1	E3 ubiquitin-protein ligase NHLRC1	E3 ubiquitin-protein ligase.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NHLRC1	Transcription factor	no		NHL_repeat, Znf_RING, 6-blade_b-propeller_TolB-like

Expression context

Cohort genes with no expression data: 0.

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
hindlimb stylopod muscle	1
islet of Langerhans	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NHLRC1	129	broad	yes	prefrontal cortex, islet of Langerhans, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NHLRC1	939

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NHLRC1	Q6VVB1	85.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Myoclonic epilepsy of Lafora	1	1268.9×	0.001	NHLRC1
Glycogen synthesis	1	815.7×	0.001	NHLRC1

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
glycogen biosynthetic process	1	936.2×	0.007	NHLRC1
regulation of protein localization to plasma membrane	1	648.1×	0.007	NHLRC1
positive regulation of protein ubiquitination	1	213.3×	0.013	NHLRC1
response to endoplasmic reticulum stress	1	166.8×	0.013	NHLRC1
protein polyubiquitination	1	115.4×	0.014	NHLRC1
autophagy	1	110.1×	0.014	NHLRC1
regulation of gene expression	1	83.4×	0.015	NHLRC1
ubiquitin-dependent protein catabolic process	1	74.2×	0.015	NHLRC1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	NHLRC1

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
NHLRC1	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	NHLRC1

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)
NHLRC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.