Brugada syndrome 7

Summary

Brugada syndrome 7 (MONDO:0013146) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 130

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Brugada syndrome 7
Mondo ID	MONDO:0013146
MeSH	C567734
OMIM	613120
DOID	DOID:0110224
UMLS	C2751088
MedGen	413472
GARD	0015620
Is cancer (heuristic)	no

Also known as: BRGDA7 · Brugada syndrome 7 · Brugada syndrome caused by mutation in SCN3B · Brugada syndrome type 7 · SCN3B Brugada syndrome

Data availability: 130 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 7

Related subtypes (8): Brugada syndrome 1, Brugada syndrome 2, Brugada syndrome 3, Brugada syndrome 4, Brugada syndrome 5, Brugada syndrome 6, 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

130 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 43 likely benign, 10 conflicting classifications of pathogenicity, 7 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1005948	NM_001040151.2(SCN3B):c.73G>T (p.Val25Leu)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376285	NM_001040151.2(SCN3B):c.106G>A (p.Val36Met)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190884	NM_001040151.2(SCN3B):c.629C>T (p.Ala210Val)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190886	NM_001040151.2(SCN3B):c.328G>A (p.Val110Ile)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190888	NM_001040151.2(SCN3B):c.416G>A (p.Arg139Gln)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2470	NM_001040151.2(SCN3B):c.29T>C (p.Leu10Pro)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4614926	NM_001040151.2(SCN3B):c.584C>G (p.Ala195Gly)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
519233	NM_001040151.2(SCN3B):c.415C>T (p.Arg139Trp)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
642346	NM_001040151.2(SCN3B):c.583G>A (p.Ala195Thr)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
950266	NM_001040151.2(SCN3B):c.410C>T (p.Thr137Met)	SCN3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047664	NM_001040151.2(SCN3B):c.14A>G (p.Asn5Ser)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056663	NM_001040151.2(SCN3B):c.446C>G (p.Ala149Gly)	SCN3B	Uncertain significance	criteria provided, single submitter
1305211	NM_001040151.2(SCN3B):c.205G>A (p.Gly69Ser)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1390308	NM_001040151.2(SCN3B):c.31G>A (p.Ala11Thr)	SCN3B	Uncertain significance	criteria provided, single submitter
140596	NM_001040151.2(SCN3B):c.161T>G (p.Val54Gly)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
140597	NM_001040151.2(SCN3B):c.389C>T (p.Ala130Val)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1411586	NM_001040151.2(SCN3B):c.232C>T (p.Arg78Trp)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1412157	NC_000011.9:g.(?123504851)(123516478_?)dup	SCN3B	Uncertain significance	criteria provided, single submitter
1417250	NM_001040151.2(SCN3B):c.38T>C (p.Leu13Pro)	SCN3B	Uncertain significance	criteria provided, single submitter
1436068	NM_001040151.2(SCN3B):c.233G>A (p.Arg78Gln)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1438625	NM_001040151.2(SCN3B):c.295G>A (p.Asp99Asn)	SCN3B	Uncertain significance	criteria provided, single submitter
1444334	NM_001040151.2(SCN3B):c.260C>G (p.Pro87Arg)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1460899	NM_001040151.2(SCN3B):c.46A>G (p.Ile16Val)	SCN3B	Uncertain significance	criteria provided, single submitter
1474456	NM_001040151.2(SCN3B):c.392A>G (p.His131Arg)	SCN3B	Uncertain significance	criteria provided, single submitter
1484460	NM_001040151.2(SCN3B):c.584+2dup	SCN3B	Uncertain significance	criteria provided, single submitter
1486045	NM_001040151.2(SCN3B):c.392_397del (p.His131_Arg132del)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1495811	NM_001040151.2(SCN3B):c.219+2T>C	SCN3B	Uncertain significance	criteria provided, single submitter
1496868	NM_001040151.2(SCN3B):c.55+3A>G	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1504135	NM_001040151.2(SCN3B):c.256del (p.Ser86fs)	SCN3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1714500	NM_001040151.2(SCN3B):c.241C>T (p.His81Tyr)	SCN3B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SCN3B	Limited	Autosomal dominant	Brugada syndrome 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN3B	Orphanet:130	Brugada syndrome
SCN3B	Orphanet:334	Hereditary atrial fibrillation

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
SCN3B	HGNC:20665	ENSG00000166257	Q9NY72	Sodium channel regulatory subunit beta-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN3B	Sodium channel regulatory subunit beta-3	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization 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.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN3B	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set

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
cortical plate	1
middle temporal gyrus	1
orbitofrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN3B	193	broad	marker	middle temporal gyrus, orbitofrontal cortex, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN3B	2,219

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN3B	Q9NY72	3

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	SCN3B
Phase 0 - rapid depolarisation	1	346.1×	0.012	SCN3B
L1CAM interactions	1	120.2×	0.018	SCN3B
Cardiac conduction	1	108.8×	0.018	SCN3B
Muscle contraction	1	77.2×	0.021	SCN3B
Axon guidance	1	45.1×	0.027	SCN3B
Nervous system development	1	42.9×	0.027	SCN3B
Developmental Biology	1	14.5×	0.069	SCN3B

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
regulation of ventricular cardiac muscle cell membrane depolarization	1	2808.7×	0.002	SCN3B
SA node cell action potential	1	2808.7×	0.002	SCN3B
regulation of atrial cardiac muscle cell membrane depolarization	1	1872.4×	0.002	SCN3B
membrane depolarization during action potential	1	1685.2×	0.002	SCN3B
atrial cardiac muscle cell action potential	1	1685.2×	0.002	SCN3B
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.002	SCN3B
ventricular cardiac muscle cell action potential	1	991.3×	0.002	SCN3B
positive regulation of sodium ion transport	1	842.6×	0.002	SCN3B
positive regulation of heart rate	1	702.2×	0.002	SCN3B
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	SCN3B
membrane depolarization	1	510.7×	0.003	SCN3B
cardiac muscle contraction	1	401.2×	0.003	SCN3B
regulation of heart rate by cardiac conduction	1	374.5×	0.003	SCN3B
sodium ion transport	1	271.8×	0.004	SCN3B
sodium ion transmembrane transport	1	203.0×	0.006	SCN3B
protein localization to plasma membrane	1	108.7×	0.010	SCN3B
nervous system development	1	45.9×	0.022	SCN3B

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
SCN3B	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	1	SCN3B
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
SCN3B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.