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Atlas / Disease / Brugada syndrome 3

Brugada syndrome 3

disease
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Also known as BRGDA3Brugada syndrome caused by mutation in CACNA1CBrugada syndrome type 3CACNA1C Brugada syndrome

Summary

Brugada syndrome 3 (MONDO:0012742) is a disease with 2 cohort genes.

At a glance

  • Cohort genes: 2
  • ClinVar variants: 134

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameBrugada syndrome 3
Mondo IDMONDO:0012742
MeSHC567509
OMIM611875
DOIDDOID:0110220
UMLSC2678478
MedGen395633
GARD0010361
Is cancer (heuristic)no

Also known as: BRGDA3 · Brugada syndrome 3 · Brugada syndrome caused by mutation in CACNA1C · Brugada syndrome type 3 · CACNA1C Brugada syndrome

Data availability: 134 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › Brugada syndrome › Brugada syndrome 3

Related subtypes (8): Brugada syndrome 1, Brugada syndrome 2, Brugada syndrome 4, Brugada syndrome 5, Brugada syndrome 6, Brugada syndrome 7, Brugada syndrome 8, Brugada syndrome 9

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

134 retrieved; paginated sample, class counts are floors:

59 conflicting classifications of pathogenicity, 47 uncertain significance, 9 likely benign, 9 benign/likely benign, 3 benign, 3 likely pathogenic, 2 pathogenic, 2 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
17632NM_000719.7(CACNA1C):c.1216G>A (p.Gly406Arg)CACNA1CPathogeniccriteria provided, multiple submitters, no conflicts
17635NM_000719.7(CACNA1C):c.116C>T (p.Ala39Val)CACNA1CPathogenicno assertion criteria provided
190633NM_001167623.2(CACNA1C):c.1216G>A (p.Gly406Arg)CACNA1CPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
3382740NM_000719.7(CACNA1C):c.1832T>C (p.Met611Thr)CACNA1CPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
3382973NM_000719.7(CACNA1C):c.3487G>A (p.Gly1163Ser)CACNA1CLikely pathogeniccriteria provided, single submitter
3392514NM_000719.7(CACNA1C):c.794T>A (p.Met265Lys)CACNA1CLikely pathogeniccriteria provided, single submitter
973262NM_000719.7(CACNA1C):c.722T>C (p.Val241Ala)CACNA1CLikely pathogeniccriteria provided, multiple submitters, no conflicts
1003227NM_000719.7(CACNA1C):c.6091G>A (p.Gly2031Ser)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1015055NM_000719.7(CACNA1C):c.82G>A (p.Ala28Thr)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1053141NM_000719.7(CACNA1C):c.1026C>T (p.Gly342=)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1432134NM_000719.7(CACNA1C):c.5852C>G (p.Pro1951Arg)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1468528NM_000719.7(CACNA1C):c.4943C>T (p.Ala1648Val)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1525632NM_000719.7(CACNA1C):c.5987C>T (p.Ala1996Val)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
17634NM_000719.7(CACNA1C):c.1468G>A (p.Gly490Arg)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
180285NM_000719.7(CACNA1C):c.5444G>C (p.Arg1815Thr)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190614NM_001167623.2(CACNA1C):c.3883A>G (p.Ile1295Val)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190626NM_000719.7(CACNA1C):c.5885G>A (p.Arg1962Gln)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190628NM_000719.7(CACNA1C):c.5975G>T (p.Cys1992Phe)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190631NM_000719.7(CACNA1C):c.911T>C (p.Ile304Thr)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190639NM_000719.7(CACNA1C):c.1485C>A (p.His495Gln)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190640NM_000719.7(CACNA1C):c.1487G>A (p.Arg496Gln)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190679NM_000719.7(CACNA1C):c.98A>G (p.Asn33Ser)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190683NM_000719.7(CACNA1C):c.236C>T (p.Thr79Met)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190686NM_000719.7(CACNA1C):c.5198C>T (p.Ala1733Val)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190688NM_000719.7(CACNA1C):c.5338C>T (p.Arg1780Cys)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190694NM_000719.7(CACNA1C):c.5026GAG[2] (p.Glu1678del)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190710NM_000719.7(CACNA1C):c.2T>C (p.Met1Thr)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
190711NM_000719.7(CACNA1C):c.15_16del (p.Thr6fs)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
191427NM_000719.7(CACNA1C):c.5731G>C (p.Gly1911Arg)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications
195932NM_000719.7(CACNA1C):c.3234C>T (p.Asp1078=)CACNA1CConflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
CACNA1CSupportiveAutosomal dominantBrugada syndrome13

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CACNA1COrphanet:101016Romano-Ward syndrome
CACNA1COrphanet:130Brugada syndrome
CACNA1COrphanet:528084Non-specific syndromic intellectual disability
CACNA1COrphanet:595098Timothy syndrome type 1
CACNA1COrphanet:595105Timothy syndrome type 2
CACNA1COrphanet:595109Atypical Timothy syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CACNA1CHGNC:1390ENSG00000151067Q13936Voltage-dependent L-type calcium channel subunit alpha-1Cgencc,clinvar
ITFG2-AS1HGNC:53128ENSG00000258325ITFG2 antisense RNA 1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CACNA1CVoltage-dependent L-type calcium channel subunit alpha-1CPore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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.

FamilyGenesFoldFDR
Ion channel155.8×0.036
Other/Unknown10.9×0.805

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CACNA1CIon channelyesVDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
ITFG2-AS1Other/Unknownno

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)2
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart1
muscle layer of sigmoid colon1
right coronary artery1
left testis1
male germ line stem cell (sensu Vertebrata) in testis1
primordial germ cell in gonad1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CACNA1C134broadmarkerapex of heart, right coronary artery, muscle layer of sigmoid colon
ITFG2-AS1131tissue_specificyesmale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CACNA1C3,145
ITFG2-AS10

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CACNA1CQ1393633

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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.

PathwayCohort genesFoldFDRSample cohort genes
Phase 2 - plateau phase1761.3×0.010CACNA1C
Adrenaline,noradrenaline inhibits insulin secretion1393.8×0.010CACNA1C
Phase 0 - rapid depolarisation1346.1×0.010CACNA1C
NCAM signaling for neurite out-growth1271.9×0.010CACNA1C
NCAM1 interactions1248.3×0.010CACNA1C
Regulation of insulin secretion1219.6×0.010CACNA1C
Integration of energy metabolism1175.7×0.011CACNA1C
Cardiac conduction1108.8×0.015CACNA1C
Muscle contraction177.2×0.019CACNA1C
Axon guidance145.1×0.028CACNA1C
Nervous system development142.9×0.028CACNA1C
Developmental Biology114.5×0.075CACNA1C
Metabolism111.6×0.086CACNA1C

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
calcium ion transmembrane transport via high voltage-gated calcium channel15617.3×0.001CACNA1C
membrane depolarization during atrial cardiac muscle cell action potential15617.3×0.001CACNA1C
immune system development14213.0×0.001CACNA1C
positive regulation of adenylate cyclase activity13370.4×0.001CACNA1C
membrane depolarization during AV node cell action potential13370.4×0.001CACNA1C
positive regulation of muscle contraction12407.4×0.001CACNA1C
cardiac conduction11685.2×0.001CACNA1C
membrane depolarization during cardiac muscle cell action potential11404.3×0.001CACNA1C
cell communication by electrical coupling involved in cardiac conduction11404.3×0.001CACNA1C
regulation of ventricular cardiac muscle cell action potential11404.3×0.001CACNA1C
calcium ion transport into cytosol11203.7×0.002CACNA1C
cardiac muscle cell action potential involved in contraction1702.2×0.002CACNA1C
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion1674.1×0.002CACNA1C
calcium ion import across plasma membrane1543.6×0.003CACNA1C
embryonic forelimb morphogenesis1495.6×0.003CACNA1C
regulation of heart rate by cardiac conduction1374.5×0.003CACNA1C
camera-type eye development1358.6×0.003CACNA1C
calcium ion transmembrane transport1210.7×0.005CACNA1C
positive regulation of cytosolic calcium ion concentration1117.0×0.009CACNA1C
heart development178.8×0.013CACNA1C

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
CACNA1CREMIFENTANIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
CACNA1C854
ITFG2-AS100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
REMIFENTANIL4CACNA1C
BEPRIDIL4CACNA1C
CLOTRIMAZOLE4CACNA1C
PROPIVERINE4CACNA1C
DIBUCAINE4CACNA1C
IMIPRAMINE4CACNA1C
DULOXETINE4CACNA1C
QUINIDINE4CACNA1C
ESTRADIOL4CACNA1C
TOLTERODINE4CACNA1C
PIMOZIDE4CACNA1C
NIMODIPINE4CACNA1C
NICARDIPINE4CACNA1C
AMLODIPINE4CACNA1C
VARDENAFIL4CACNA1C
CLEMASTINE4CACNA1C
ISRADIPINE4CACNA1C
TERFENADINE4CACNA1C
NISOLDIPINE4CACNA1C
SOLIFENACIN4CACNA1C
PINAVERIUM4CACNA1C
SILDENAFIL4CACNA1C
NIFEDIPINE4CACNA1C
XANOMELINE4CACNA1C
DILTIAZEM4CACNA1C
PRENYLAMINE4CACNA1C
OLICERIDINE4CACNA1C
PROPRANOLOL4CACNA1C
ALVIMOPAN4CACNA1C
ASTEMIZOLE4CACNA1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
CACNA1C575Binding:319, Functional:211, Toxicity:26, ADMET:19

Cohort genes with high screening signal

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

SymbolChEMBL assays
CACNA1C575

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

30 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)
REMIFENTANIL4CACNA1C
BEPRIDIL4CACNA1C
CLOTRIMAZOLE4CACNA1C
PROPIVERINE4CACNA1C
DIBUCAINE4CACNA1C
IMIPRAMINE4CACNA1C
DULOXETINE4CACNA1C
QUINIDINE4CACNA1C
ESTRADIOL4CACNA1C
TOLTERODINE4CACNA1C
PIMOZIDE4CACNA1C
NIMODIPINE4CACNA1C
NICARDIPINE4CACNA1C
AMLODIPINE4CACNA1C
VARDENAFIL4CACNA1C
CLEMASTINE4CACNA1C
ISRADIPINE4CACNA1C
TERFENADINE4CACNA1C
NISOLDIPINE4CACNA1C
SOLIFENACIN4CACNA1C
PINAVERIUM4CACNA1C
SILDENAFIL4CACNA1C
NIFEDIPINE4CACNA1C
XANOMELINE4CACNA1C
DILTIAZEM4CACNA1C
PRENYLAMINE4CACNA1C
OLICERIDINE4CACNA1C
PROPRANOLOL4CACNA1C
ALVIMOPAN4CACNA1C
ASTEMIZOLE4CACNA1C

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CACNA1C
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1ITFG2-AS1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
ITFG2-AS10—

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