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Episodic pain syndrome, familial, 2

disease
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Also known as episodic pain syndrome, familial, type 2familial episodic pain syndrome caused by mutation in SCN10AFEPS2SCN10A familial episodic pain syndrome

Summary

Episodic pain syndrome, familial, 2 (MONDO:0014246) is a disease caused by SCN10A (GenCC Strong), with 1 cohort gene.

At a glance

  • Causal gene: SCN10A (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 136

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameepisodic pain syndrome, familial, 2
Mondo IDMONDO:0014246
OMIM615551
DOIDDOID:0111730
UMLSC3809893
MedGen816223
GARD0018440
Is cancer (heuristic)no

Also known as: episodic pain syndrome, familial, 2 · episodic pain syndrome, familial, type 2 · familial episodic pain syndrome caused by mutation in SCN10A · FEPS2 · SCN10A familial episodic pain syndrome

Data availability: 136 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › hereditary peripheral neuropathy › familial episodic pain syndrome › episodic pain syndrome, familial, 2

Related subtypes (2): familial episodic pain syndrome with predominantly upper body involvement, familial episodic pain syndrome with predominantly lower limb involvement

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

136 retrieved; paginated sample, class counts are floors:

64 uncertain significance, 41 conflicting classifications of pathogenicity, 12 benign/likely benign, 11 benign, 7 likely benign, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
4688148NM_006514.4(SCN10A):c.2231T>A (p.Leu744Gln)SCN10ALikely pathogeniccriteria provided, single submitter
1042304NM_006514.4(SCN10A):c.2965G>A (p.Ala989Thr)LOC110121288Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
407748NM_006514.4(SCN10A):c.2842G>C (p.Val948Leu)LOC110121288Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
463247NM_006514.4(SCN10A):c.3238G>A (p.Asp1080Asn)LOC110121288Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
463249NM_006514.4(SCN10A):c.3482T>C (p.Met1161Thr)LOC110121288Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
532064NM_006514.4(SCN10A):c.3417G>C (p.Trp1139Cys)LOC110121288Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1006881NM_006514.4(SCN10A):c.2616G>A (p.Thr872=)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1046224NM_006514.4(SCN10A):c.2221C>G (p.Leu741Val)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1310896NM_006514.4(SCN10A):c.5023C>A (p.Pro1675Thr)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1380283NM_006514.4(SCN10A):c.5588G>A (p.Arg1863Gln)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1429429NM_006514.4(SCN10A):c.4607C>G (p.Thr1536Arg)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1429567NM_006514.4(SCN10A):c.3727G>A (p.Val1243Met)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1524842NM_006514.4(SCN10A):c.4657+5G>ASCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
240671NM_006514.4(SCN10A):c.365C>T (p.Thr122Met)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
240673NM_006514.4(SCN10A):c.3803G>A (p.Arg1268Gln)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
373688NM_006514.4(SCN10A):c.3474C>G (p.Ile1158Met)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
376797NM_006514.4(SCN10A):c.905G>A (p.Arg302Gln)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
407745NM_006514.4(SCN10A):c.1858G>A (p.Val620Ile)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
414629NM_006514.4(SCN10A):c.1138G>A (p.Val380Ile)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
418471NM_006514.4(SCN10A):c.4849G>T (p.Val1617Phe)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
420025NM_006514.4(SCN10A):c.2441G>A (p.Arg814His)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
430247NM_006514.4(SCN10A):c.5548C>T (p.Gln1850Ter)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
449360NM_006514.4(SCN10A):c.724T>A (p.Ser242Thr)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
463232NM_006514.4(SCN10A):c.1370A>G (p.Glu457Gly)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
463239NM_006514.4(SCN10A):c.2428G>T (p.Gly810Trp)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
463259NM_006514.4(SCN10A):c.4709C>T (p.Thr1570Met)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
463260NM_006514.4(SCN10A):c.472T>G (p.Tyr158Asp)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
463273NM_006514.4(SCN10A):c.883C>T (p.Pro295Ser)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
532059NM_006514.4(SCN10A):c.2266C>T (p.Arg756Trp)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
532083NM_006514.4(SCN10A):c.5200G>A (p.Glu1734Lys)SCN10AConflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 6 · 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.

GeneClassificationInheritanceDiseaseRecords
SCN10AStrongAutosomal dominantepisodic pain syndrome, familial, 26

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SCN10AOrphanet:101016Romano-Ward syndrome
SCN10AOrphanet:130Brugada syndrome
SCN10AOrphanet:306577Hereditary sodium channelopathy-related small fibers neuropathy
SCN10AOrphanet:46348Paroxysmal extreme pain disorder
SCN10AOrphanet:88642Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN10AOrphanet:90026Primary erythromelalgia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SCN10AHGNC:10582ENSG00000185313Q9Y5Y9Sodium channel protein type 10 subunit alphagencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SCN10ASodium channel protein type 10 subunit alphaTetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes.

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.

FamilyGenesFoldFDR
Ion channel1111.5×0.009

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SCN10AIon channelyesNa_channel_asu, Ion_trans_dom, Na_trans_assoc_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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
diaphragm1
olfactory bulb1
type B pancreatic cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SCN10A21markertype B pancreatic cell, olfactory bulb, diaphragm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SCN10A1,802

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SCN10AQ9Y5Y98

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.

PathwayCohort genesFoldFDRSample cohort genes
Interaction between L1 and Ankyrins1368.4×0.012SCN10A
Phase 0 - rapid depolarisation1346.1×0.012SCN10A
L1CAM interactions1120.2×0.018SCN10A
Cardiac conduction1108.8×0.018SCN10A
Muscle contraction177.2×0.021SCN10A
Axon guidance145.1×0.027SCN10A
Nervous system development142.9×0.027SCN10A
Developmental Biology114.5×0.069SCN10A

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 termCohort genesFoldFDRSample cohort genes
bundle of His cell action potential18426.0×0.001SCN10A
AV node cell action potential14213.0×0.001SCN10A
regulation of atrial cardiac muscle cell membrane depolarization11872.4×0.002SCN10A
membrane depolarization during action potential11685.2×0.002SCN10A
sensory perception11404.3×0.002SCN10A
regulation of cardiac muscle contraction1887.0×0.002SCN10A
regulation of monoatomic ion transmembrane transport1732.7×0.002SCN10A
cardiac muscle cell action potential involved in contraction1702.2×0.002SCN10A
regulation of heart rate1468.1×0.003SCN10A
odontogenesis of dentin-containing tooth1300.9×0.004SCN10A
sodium ion transmembrane transport1203.0×0.005SCN10A

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.

SymbolExample approved molecule
SCN10AIMIPRAMINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
SCN10A214

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
IMIPRAMINE4SCN10A
SERTINDOLE4SCN10A
PIMOZIDE4SCN10A
NIFEDIPINE4SCN10A
DILTIAZEM4SCN10A
MIBEFRADIL4SCN10A
HALOPERIDOL4SCN10A
MEXILETINE4SCN10A
AMITRIPTYLINE4SCN10A
AMIODARONE4SCN10A
CHLORPROMAZINE4SCN10A
LAMOTRIGINE4SCN10A
TEDISAMIL3SCN10A
NITRENDIPINE3SCN10A
AJMALINE3SCN10A
VIXOTRIGINE3SCN10A
ELECLAZINE3SCN10A
CIFENLINE2SCN10A
PF-045310832SCN10A
FUNAPIDE2SCN10A
PF-063055911SCN10A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
SCN10A144Binding:124, Functional:16, ADMET:4

Cohort genes with high screening signal

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

SymbolChEMBL assays
SCN10A144

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

21 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.

CompoundMax phaseCohort target (bioactivity)
IMIPRAMINE4SCN10A
SERTINDOLE4SCN10A
PIMOZIDE4SCN10A
NIFEDIPINE4SCN10A
DILTIAZEM4SCN10A
MIBEFRADIL4SCN10A
HALOPERIDOL4SCN10A
MEXILETINE4SCN10A
AMITRIPTYLINE4SCN10A
AMIODARONE4SCN10A
CHLORPROMAZINE4SCN10A
LAMOTRIGINE4SCN10A
TEDISAMIL3SCN10A
NITRENDIPINE3SCN10A
AJMALINE3SCN10A
VIXOTRIGINE3SCN10A
ELECLAZINE3SCN10A
CIFENLINE2SCN10A
PF-045310832SCN10A
FUNAPIDE2SCN10A
PF-063055911SCN10A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1SCN10A
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 69

This page pulls from 69 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot