Progressive myoclonic epilepsy type 7

Summary

Progressive myoclonic epilepsy type 7 (MONDO:0014521) is a disease caused by KCNC1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KCNC1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 452

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	progressive myoclonic epilepsy type 7
Mondo ID	MONDO:0014521
OMIM	616187
Orphanet	435438
DOID	DOID:0111447
NCIT	C142804
UMLS	C4015420
MedGen	863857
GARD	0017715
Is cancer (heuristic)	no

Also known as: epilepsy, progressive myoclonic 7 · epilepsy, progressive myoclonic type 7 · EPM7 · KCNC1 progressive myoclonic epilepsy · MEAK · meak · myoclonus epilepsy and ataxia due to potassium channel mutation · PME type 7 · progressive myoclonic epilepsy caused by mutation in KCNC1 · progressive myoclonic epilepsy due to KV3.1 deficiency · progressive myoclonus epilepsy type 7

Data availability: 452 ClinVar variants · 5 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › progressive myoclonic epilepsy type 7

Related subtypes (53): cerebellar ataxia, chronic tic disorder, choreatic disease, extrapyramidal and movement disease, benign shuddering attacks, transient tic disorder, essential tremor, lingual-facial-buccal dyskinesia, kuru, inherited Creutzfeldt-Jakob disease, Tourette syndrome, clonic hemifacial spasm, Huntington disease, multiple system atrophy, spinal muscular atrophy-progressive myoclonic epilepsy syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, hereditary geniospasm, tremor-nystagmus-duodenal ulcer syndrome, arthrogryposis, Lafora disease, Unverricht-Lundborg syndrome, neuronal intranuclear inclusion disease, Huntington disease-like 3, brain-lung-thyroid syndrome, myoclonus, familial, proximal myopathy with extrapyramidal signs, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, progressive non-fluent aphasia, opsoclonus-myoclonus syndrome, isolated facial myokymia, primary orthostatic tremor, familial congenital mirror movements, neuroacanthocytosis, behavioral variant of frontotemporal dementia, frontotemporal dementia with motor neuron disease, hyperekplexia, intellectual disability-hyperkinetic movement-truncal ataxia syndrome, neurodegeneration with brain iron accumulation, Huntington disease-like syndrome due to C9ORF72 expansions, variably protease-sensitive prionopathy, corticobasal syndrome, sensorineural hearing loss-early graying-essential tremor syndrome, progressive supranuclear palsy, Sandifer syndrome, psychogenic movement disorders, epilepsy with myoclonic absences, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, childhood-onset benign chorea with striatal involvement, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, PRRT2-associated paroxysmal movement disorder, SLC6A3-related dopamine transporter deficiency syndrome, dyskinesia with orofacial involvement, autosomal dominant, complex movement disorder with or without neurodevelopmental features

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

452 retrieved; paginated sample, class counts are floors:

206 likely benign, 204 uncertain significance, 13 conflicting classifications of pathogenicity, 10 benign/likely benign, 7 benign, 7 likely pathogenic, 4 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1367356	NM_001112741.2(KCNC1):c.1196C>T (p.Thr399Met)	KCNC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162519	NM_001112741.2(KCNC1):c.959G>A (p.Arg320His)	KCNC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2856264	NM_001112741.2(KCNC1):c.1199C>A (p.Thr400Asn)	KCNC1	Pathogenic	criteria provided, single submitter
426760	NM_001112741.2(KCNC1):c.1273G>A (p.Val425Met)	KCNC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488536	NM_001112741.2(KCNC1):c.1262C>T (p.Ala421Val)	KCNC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320194	NM_001112741.2(KCNC1):c.490C>T (p.Arg164Trp)	KCNC1	Likely pathogenic	criteria provided, single submitter
2575090	NM_001112741.2(KCNC1):c.1023C>G (p.Ser341Arg)	KCNC1	Likely pathogenic	criteria provided, single submitter
568146	NM_001112741.2(KCNC1):c.691A>G (p.Thr231Ala)	KCNC1	Likely pathogenic	criteria provided, single submitter
658535	NM_001112741.2(KCNC1):c.108del (p.Trp36fs)	KCNC1	Likely pathogenic	criteria provided, single submitter
692088	NM_001112741.2(KCNC1):c.1370del (p.Lys457fs)	KCNC1	Likely pathogenic	criteria provided, single submitter
813805	NM_001112741.2(KCNC1):c.1294G>C (p.Val432Leu)	KCNC1	Likely pathogenic	criteria provided, single submitter
938939	NM_001112741.2(KCNC1):c.1538C>T (p.Ala513Val)	KCNC1	Likely pathogenic	criteria provided, single submitter
1058747	NM_001112741.2(KCNC1):c.806A>G (p.Asn269Ser)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1659253	NM_001112741.2(KCNC1):c.1504+12C>G	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218659	NM_001112741.2(KCNC1):c.1426G>A (p.Val476Ile)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2603772	NM_001112741.2(KCNC1):c.1204G>A (p.Gly402Ser)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3340779	NM_001112741.2(KCNC1):c.1066G>A (p.Val356Met)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392871	NM_001112741.2(KCNC1):c.1294G>A (p.Val432Met)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475351	NM_001112741.2(KCNC1):c.1450C>G (p.Gln484Glu)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475356	NM_001112741.2(KCNC1):c.494C>T (p.Pro165Leu)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
578002	NM_001112741.2(KCNC1):c.709C>T (p.Arg237Trp)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580602	NM_001112741.2(KCNC1):c.1619G>A (p.Arg540His)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
590165	NM_001112741.2(KCNC1):c.1585G>A (p.Asp529Asn)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
661955	NM_001112741.2(KCNC1):c.421G>T (p.Asp141Tyr)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
856458	NM_001112741.2(KCNC1):c.1015C>T (p.Arg339Ter)	KCNC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
999235	NC_000011.9:g.(?17552691)(19213995_?)dup	CSRP3	Uncertain significance	criteria provided, single submitter
1000486	NM_001112741.2(KCNC1):c.1607G>A (p.Arg536His)	KCNC1	Uncertain significance	criteria provided, single submitter
1009942	NM_001112741.2(KCNC1):c.1537G>A (p.Ala513Thr)	KCNC1	Uncertain significance	criteria provided, single submitter
1011041	NM_001112741.2(KCNC1):c.1649C>T (p.Ser550Leu)	KCNC1	Uncertain significance	criteria provided, single submitter
1014282	NM_001112741.2(KCNC1):c.428G>A (p.Gly143Asp)	KCNC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
KCNC1	Definitive	Autosomal dominant	progressive myoclonic epilepsy type 7	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNC1	Orphanet:435438	Progressive myoclonic epilepsy type 7
CSRP3	Orphanet:154	Familial isolated dilated cardiomyopathy

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
KCNC1	HGNC:6233	ENSG00000129159	P48547	Voltage-gated potassium channel KCNC1	gencc,clinvar
CSRP3	HGNC:2472	ENSG00000129170	P50461	Cysteine and glycine-rich protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNC1	Voltage-gated potassium channel KCNC1	Voltage-gated potassium channel that opens in response to the voltage difference across the membrane and through which potassium ions pass in accordance with their electrochemical gradient.
CSRP3	Cysteine and glycine-rich protein 3	Positive regulator of myogenesis.

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
Ion channel	1	55.8×	0.036
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNC1	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
CSRP3	Transcription factor	no		Znf_LIM

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
heart right ventricle	1
left ventricle myocardium	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNC1	186	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CSRP3	173	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, heart right ventricle, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNC1	3,000
CSRP3	1,376

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNC1	P48547	10
CSRP3	P50461	2

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
Voltage gated Potassium channels	1	243.0×	0.011	KCNC1
Potassium Channels	1	134.3×	0.011	KCNC1
Neuronal System	1	44.3×	0.023	KCNC1

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
positive regulation of actin filament severing	1	8426.0×	0.003	CSRP3
negative regulation of actin filament severing	1	4213.0×	0.003	CSRP3
response to nerve growth factor	1	2808.7×	0.003	KCNC1
globus pallidus development	1	1685.2×	0.003	KCNC1
muscle tissue development	1	1685.2×	0.003	CSRP3
T-tubule organization	1	1404.3×	0.003	CSRP3
phospholipase C/protein kinase C signal transduction	1	1404.3×	0.003	CSRP3
detection of muscle stretch	1	1203.7×	0.003	CSRP3
response to light intensity	1	1053.2×	0.003	KCNC1
response to potassium ion	1	1053.2×	0.003	KCNC1
response to fibroblast growth factor	1	1053.2×	0.003	KCNC1
response to amine	1	936.2×	0.003	KCNC1
establishment of protein localization to organelle	1	936.2×	0.003	CSRP3
cardiac muscle hypertrophy	1	842.6×	0.003	CSRP3
cardiac myofibril assembly	1	648.1×	0.004	CSRP3
optic nerve development	1	601.9×	0.004	KCNC1
regulation of the force of heart contraction	1	495.6×	0.005	CSRP3
positive regulation of potassium ion transmembrane transport	1	495.6×	0.005	KCNC1
cardiac muscle tissue development	1	443.5×	0.005	CSRP3
corpus callosum development	1	421.3×	0.005	KCNC1
response to auditory stimulus	1	366.4×	0.005	KCNC1
muscle cell cellular homeostasis	1	324.1×	0.005	CSRP3
regulation of protein localization to plasma membrane	1	324.1×	0.005	CSRP3
negative regulation of myoblast differentiation	1	312.1×	0.005	CSRP3
protein tetramerization	1	312.1×	0.005	KCNC1
cardiac muscle contraction	1	200.6×	0.008	CSRP3
sarcomere organization	1	191.5×	0.008	CSRP3
positive regulation of myoblast differentiation	1	183.2×	0.008	CSRP3
action potential	1	179.3×	0.008	KCNC1
cerebellum development	1	179.3×	0.008	KCNC1

Therapeutics

Drug target analysis

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

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
KCNC1	0	0
CSRP3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNC1	28	Binding:25, Functional:2, Toxicity:1

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	1	KCNC1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CSRP3

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)
KCNC1	28	—
CSRP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.