Myoclonus, familial, 2

Summary

Myoclonus, familial, 2 (MONDO:0100092) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonus, familial, 2
Mondo ID	MONDO:0100092
OMIM	618364
UMLS	C5193056
MedGen	1683864
GARD	0026042
Is cancer (heuristic)	no

Also known as: MYOCL2

Data availability: 37 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › myoclonus, familial › myoclonus, familial, 2

Related subtypes (1): myoclonus, familial, 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

37 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 9 benign, 5 conflicting classifications of pathogenicity, 5 likely pathogenic, 4 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1399415	NM_001330260.2(SCN8A):c.632T>G (p.Val211Gly)	SCN8A	Pathogenic	criteria provided, single submitter
253297	NM_001330260.2(SCN8A):c.5615G>A (p.Arg1872Gln)	SCN8A	Pathogenic	reviewed by expert panel
623637	NM_001330260.2(SCN8A):c.5156C>G (p.Pro1719Arg)	SCN8A	Pathogenic	no assertion criteria provided
4796515	NM_001330260.2(SCN8A):c.212del (p.Asp71fs)	LOC114803470	Likely pathogenic	criteria provided, single submitter
2582519	NM_001330260.2(SCN8A):c.2935_2936delinsAA (p.Ser979Asn)	SCN8A	Likely pathogenic	criteria provided, single submitter
3024271	NC_000012.11:g.52199766_52388207del	SCN8A	Likely pathogenic	criteria provided, single submitter
3238793	NM_001330260.2(SCN8A):c.677G>C (p.Arg226Pro)	SCN8A	Likely pathogenic	criteria provided, single submitter
3238817	NM_001330260.2(SCN8A):c.4442T>A (p.Met1481Lys)	SCN8A	Likely pathogenic	criteria provided, single submitter
1016014	NM_001330260.2(SCN8A):c.2985C>A (p.Asn995Lys)	SCN8A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1039121	NM_001330260.2(SCN8A):c.1396G>A (p.Glu466Lys)	SCN8A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2580849	NM_001330260.2(SCN8A):c.1676A>G (p.His559Arg)	SCN8A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
445379	NM_001330260.2(SCN8A):c.4282-10C>G	SCN8A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579919	NM_001330260.2(SCN8A):c.5479A>G (p.Ile1827Val)	SCN8A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626165	NM_001330260.2(SCN8A):c.71A>G (p.Asn24Ser)	LOC114803470	Uncertain significance	criteria provided, multiple submitters, no conflicts
1371411	NM_001330260.2(SCN8A):c.3136G>A (p.Ala1046Thr)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1406186	NM_001330260.2(SCN8A):c.1420C>T (p.Pro474Ser)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679749	NM_001330260.2(SCN8A):c.1264C>A (p.Leu422Met)	SCN8A	Uncertain significance	criteria provided, single submitter
2441961	NM_001330260.2(SCN8A):c.5307C>A (p.Phe1769Leu)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500085	NM_001330260.2(SCN8A):c.5740G>A (p.Gly1914Ser)	SCN8A	Uncertain significance	criteria provided, single submitter
2582310	NM_001330260.2(SCN8A):c.4082C>G (p.Ser1361Cys)	SCN8A	Uncertain significance	criteria provided, single submitter
3704518	NM_001330260.2(SCN8A):c.3320A>C (p.Asn1107Thr)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
567631	NM_001330260.2(SCN8A):c.3433G>A (p.Glu1145Lys)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
659277	NM_001330260.2(SCN8A):c.1655G>C (p.Gly552Ala)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
838164	NM_001330260.2(SCN8A):c.2139A>C (p.Glu713Asp)	SCN8A	Uncertain significance	criteria provided, multiple submitters, no conflicts
139075	NM_001330260.2(SCN8A):c.141C>T (p.Asp47=)	LOC114803470	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1169384	NM_001330260.2(SCN8A):c.2545-7dup	SCN8A	Benign	criteria provided, multiple submitters, no conflicts
1221685	NM_001330260.2(SCN8A):c.4796-38C>A	SCN8A	Benign	criteria provided, multiple submitters, no conflicts
1250894	NM_001330260.2(SCN8A):c.2371-32A>C	SCN8A	Benign	criteria provided, multiple submitters, no conflicts
130242	NM_001330260.2(SCN8A):c.1833G>T (p.Arg611=)	SCN8A	Benign	criteria provided, multiple submitters, no conflicts
130246	NM_001330260.2(SCN8A):c.4122T>A (p.Thr1374=)	SCN8A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 4 · 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
SCN8A	Limited	Autosomal dominant	myoclonus, familial, 2	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN8A	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SCN8A	Orphanet:306	Self-limited infantile epilepsy
SCN8A	Orphanet:352582	Familial infantile myoclonic epilepsy
SCN8A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
SCN8A	HGNC:10596	ENSG00000196876	Q9UQD0	Sodium channel protein type 8 subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN8A	Sodium channel protein type 8 subunit alpha	Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradie…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN8A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom

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
Brodmann (1909) area 23	1
middle temporal gyrus	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN8A	194	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN8A	2,120

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN8A	Q9UQD0	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Interaction between L1 and Ankyrins	1	368.4×	0.012	SCN8A
Phase 0 - rapid depolarisation	1	346.1×	0.012	SCN8A
L1CAM interactions	1	120.2×	0.018	SCN8A
Cardiac conduction	1	108.8×	0.018	SCN8A
Muscle contraction	1	77.2×	0.021	SCN8A
Axon guidance	1	45.1×	0.027	SCN8A
Nervous system development	1	42.9×	0.027	SCN8A
Developmental Biology	1	14.5×	0.069	SCN8A

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
cardiac muscle cell action potential involved in contraction	1	702.2×	0.005	SCN8A
peripheral nervous system development	1	581.1×	0.005	SCN8A
action potential	1	358.6×	0.005	SCN8A
sodium ion transport	1	271.8×	0.005	SCN8A
myelination	1	251.5×	0.005	SCN8A
sodium ion transmembrane transport	1	203.0×	0.005	SCN8A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN8A	IMIPRAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN8A	25	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	SCN8A
SERTINDOLE	4	SCN8A
PIMOZIDE	4	SCN8A
NIFEDIPINE	4	SCN8A
DILTIAZEM	4	SCN8A
MIBEFRADIL	4	SCN8A
HALOPERIDOL	4	SCN8A
MEXILETINE	4	SCN8A
AMITRIPTYLINE	4	SCN8A
AMIODARONE	4	SCN8A
CHLORPROMAZINE	4	SCN8A
TETRACAINE	4	SCN8A
TEDISAMIL	3	SCN8A
NITRENDIPINE	3	SCN8A
AJMALINE	3	SCN8A
VIXOTRIGINE	3	SCN8A
ELECLAZINE	3	SCN8A
TETRODOTOXIN	3	SCN8A
CIFENLINE	2	SCN8A
PF-05089771	2	SCN8A
FUNAPIDE	2	SCN8A
DS-1971	2	SCN8A
ZANDATRIGINE	2	SCN8A
PF-05150122	1	SCN8A
PF-05186462	1	SCN8A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN8A	173	Binding:148, Functional:16, ADMET:7, Toxicity:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN8A	173

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

25 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)
IMIPRAMINE	4	SCN8A
SERTINDOLE	4	SCN8A
PIMOZIDE	4	SCN8A
NIFEDIPINE	4	SCN8A
DILTIAZEM	4	SCN8A
MIBEFRADIL	4	SCN8A
HALOPERIDOL	4	SCN8A
MEXILETINE	4	SCN8A
AMITRIPTYLINE	4	SCN8A
AMIODARONE	4	SCN8A
CHLORPROMAZINE	4	SCN8A
TETRACAINE	4	SCN8A
TEDISAMIL	3	SCN8A
NITRENDIPINE	3	SCN8A
AJMALINE	3	SCN8A
VIXOTRIGINE	3	SCN8A
ELECLAZINE	3	SCN8A
TETRODOTOXIN	3	SCN8A
CIFENLINE	2	SCN8A
PF-05089771	2	SCN8A
FUNAPIDE	2	SCN8A
DS-1971	2	SCN8A
ZANDATRIGINE	2	SCN8A
PF-05150122	1	SCN8A
PF-05186462	1	SCN8A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN8A
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.