Epilepsy, progressive myoclonic, 11

Summary

Epilepsy, progressive myoclonic, 11 (MONDO:0030034) is a disease caused by SEMA6B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SEMA6B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, progressive myoclonic, 11
Mondo ID	MONDO:0030034
OMIM	618876
UMLS	C5394362
MedGen	1716712
GARD	0025513
Is cancer (heuristic)	no

Also known as: EPILEPSY, PROGRESSIVE MYOCLONIC, 11 · epilepsy, progressive myoclonic, 11 · EPM11

Data availability: 35 ClinVar variants · 4 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, 11

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, 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

35 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 8 likely pathogenic, 5 benign, 5 pathogenic, 2 conflicting classifications of pathogenicity, 2 likely benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2579316	NM_032108.4(SEMA6B):c.1993del (p.Arg665fs)	SEMA6B	Pathogenic	criteria provided, multiple submitters, no conflicts
3773719	NM_032108.4(SEMA6B):c.2067_2070delinsAGCA (p.Trp689_Ala690delinsTer)	SEMA6B	Pathogenic	criteria provided, single submitter
4081865	NM_032108.4(SEMA6B):c.1957del (p.Arg653fs)	SEMA6B	Pathogenic	no assertion criteria provided
872932	NM_032108.4(SEMA6B):c.1950_1969dup (p.Arg657fs)	SEMA6B	Pathogenic	no assertion criteria provided
872933	NM_032108.4(SEMA6B):c.1976_1982del (p.Ala659fs)	SEMA6B	Pathogenic	criteria provided, single submitter
872934	NM_032108.4(SEMA6B):c.1991del (p.Gly664fs)	SEMA6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526211	NM_032108.4(SEMA6B):c.1534_1537del (p.Ala512fs)	SEMA6B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2430274	NM_032108.4(SEMA6B):c.2086C>T (p.Gln696Ter)	SEMA6B	Likely pathogenic	criteria provided, single submitter
2433296	NM_032108.4(SEMA6B):c.1739-2A>G	SEMA6B	Likely pathogenic	criteria provided, single submitter
3775309	NM_032108.4(SEMA6B):c.1977_1978delinsCT (p.Gln660Ter)	SEMA6B	Likely pathogenic	criteria provided, single submitter
3777724	NM_032108.4(SEMA6B):c.1680-2A>G	SEMA6B	Likely pathogenic	criteria provided, single submitter
4077496	NM_032108.4(SEMA6B):c.1951del (p.Val651fs)	SEMA6B	Likely pathogenic	criteria provided, single submitter
4293051	NM_032108.4(SEMA6B):c.1467dup (p.Gly490fs)	SEMA6B	Likely pathogenic	criteria provided, single submitter
4293230	NM_032108.4(SEMA6B):c.1988_1991del (p.Gly663fs)	SEMA6B	Likely pathogenic	criteria provided, single submitter
1339476	NM_032108.4(SEMA6B):c.2066G>A (p.Trp689Ter)	SEMA6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1709918	NM_032108.4(SEMA6B):c.2372C>G (p.Pro791Arg)	SEMA6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1334194	NM_032108.4(SEMA6B):c.1873del (p.Arg625fs)	SEMA6B	Uncertain significance	criteria provided, single submitter
1343254	NM_032108.4(SEMA6B):c.743T>C (p.Ile248Thr)	SEMA6B	Uncertain significance	criteria provided, single submitter
1679783	NM_032108.4(SEMA6B):c.2111C>T (p.Ser704Leu)	SEMA6B	Uncertain significance	criteria provided, single submitter
2435809	NM_032108.4(SEMA6B):c.1271+4G>T	SEMA6B	Uncertain significance	criteria provided, single submitter
3254901	NM_032108.4(SEMA6B):c.279del (p.Thr94fs)	SEMA6B	Uncertain significance	criteria provided, single submitter
3362544	NM_032108.4(SEMA6B):c.2096C>T (p.Pro699Leu)	SEMA6B	Uncertain significance	criteria provided, single submitter
3391405	NM_032108.4(SEMA6B):c.17C>T (p.Ala6Val)	SEMA6B	Uncertain significance	criteria provided, single submitter
4080002	NM_032108.4(SEMA6B):c.2361C>A (p.Phe787Leu)	SEMA6B	Uncertain significance	criteria provided, single submitter
4278034	NM_032108.4(SEMA6B):c.1612G>A (p.Gly538Ser)	SEMA6B	Uncertain significance	criteria provided, multiple submitters, no conflicts
4814101	NM_032108.4(SEMA6B):c.2377G>A (p.Ala793Thr)	SEMA6B	Uncertain significance	criteria provided, single submitter
978123	NM_032108.4(SEMA6B):c.1153T>C (p.Tyr385His)	SEMA6B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1237432	NM_032108.4(SEMA6B):c.39G>C (p.Leu13=)	SEMA6B	Benign	criteria provided, multiple submitters, no conflicts
1332939	NM_032108.4(SEMA6B):c.1601+24C>T	SEMA6B	Benign	criteria provided, multiple submitters, no conflicts
1332940	NM_032108.4(SEMA6B):c.1454+30G>T	SEMA6B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SEMA6B	Strong	Autosomal dominant	epilepsy, progressive myoclonic, 11	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEMA6B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
SEMA6B	HGNC:10739	ENSG00000167680	Q9H3T3	Semaphorin-6B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEMA6B	Semaphorin-6B	Functions as a cell surface repellent for mossy fibers of developing neurons in the hippocampus where it plays a role in axon guidance.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEMA6B	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_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
anterior cingulate cortex	1
cingulate cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEMA6B	177	ubiquitous	marker	right frontal lobe, anterior cingulate cortex, cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEMA6B	722

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEMA6B	Q9H3T3	74.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
semaphorin-plexin signaling pathway	1	401.2×	0.009	SEMA6B
neural crest cell migration	1	337.0×	0.009	SEMA6B
hippocampus development	1	230.8×	0.009	SEMA6B
central nervous system development	1	115.4×	0.013	SEMA6B
axon guidance	1	90.6×	0.013	SEMA6B
positive regulation of cell migration	1	61.7×	0.016	SEMA6B

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
SEMA6B	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	SEMA6B

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)
SEMA6B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.