Brugada syndrome 6

Summary

Brugada syndrome 6 (MONDO:0013145) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 70

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Brugada syndrome 6
Mondo ID	MONDO:0013145
MeSH	C567735
OMIM	613119
DOID	DOID:0110223
UMLS	C2751089
MedGen	413473
GARD	0015619
Is cancer (heuristic)	no

Also known as: BRGDA6 · Brugada syndrome 6 · Brugada syndrome caused by mutation in KCNE3 · Brugada syndrome type 6 · KCNE3 Brugada syndrome

Data availability: 70 ClinVar variants · 5 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 6

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

70 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 15 conflicting classifications of pathogenicity, 13 likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1041613	NM_005472.5(KCNE3):c.94C>T (p.Arg32Trp)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
126426	NM_005472.5(KCNE3):c.10A>G (p.Thr4Ala)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1783395	NM_005472.5(KCNE3):c.195G>A (p.Met65Ile)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1791148	NM_005472.5(KCNE3):c.242G>A (p.Arg81His)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190800	NM_005472.5(KCNE3):c.20C>T (p.Thr7Met)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2180362	NM_005472.5(KCNE3):c.140G>A (p.Arg47Gln)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264211	NM_005472.5(KCNE3):c.26C>T (p.Thr9Ile)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
402993	NM_005472.5(KCNE3):c.158G>A (p.Arg53His)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
470686	NM_005472.5(KCNE3):c.95G>A (p.Arg32Gln)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523951	NM_005472.5(KCNE3):c.69del (p.Thr24fs)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5541	NM_005472.5(KCNE3):c.248G>A (p.Arg83His)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5542	NM_005472.5(KCNE3):c.296G>A (p.Arg99His)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
582464	NM_005472.5(KCNE3):c.116C>G (p.Pro39Arg)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
658553	NM_005472.5(KCNE3):c.49G>A (p.Val17Met)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
972690	NM_005472.5(KCNE3):c.241C>T (p.Arg81Cys)	KCNE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1003756	NM_005472.5(KCNE3):c.304A>G (p.Met102Val)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1010885	NM_005472.5(KCNE3):c.113G>A (p.Gly38Glu)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035425	NM_005472.5(KCNE3):c.222C>G (p.Ser74Arg)	KCNE3	Uncertain significance	criteria provided, single submitter
1053155	NM_005472.5(KCNE3):c.35A>G (p.Glu12Gly)	KCNE3	Uncertain significance	criteria provided, single submitter
1402058	NM_005472.5(KCNE3):c.158G>T (p.Arg53Leu)	KCNE3	Uncertain significance	criteria provided, single submitter
1406921	NM_005472.5(KCNE3):c.248G>C (p.Arg83Pro)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1475770	NM_005472.5(KCNE3):c.25A>G (p.Thr9Ala)	KCNE3	Uncertain significance	criteria provided, single submitter
1477151	NM_005472.5(KCNE3):c.134A>C (p.Glu45Ala)	KCNE3	Uncertain significance	criteria provided, single submitter
1489105	NM_005472.5(KCNE3):c.194T>C (p.Met65Thr)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1763229	NM_005472.5(KCNE3):c.83A>G (p.Asn28Ser)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1766493	NM_005472.5(KCNE3):c.92G>A (p.Cys31Tyr)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1771720	NM_005472.5(KCNE3):c.139C>G (p.Arg47Gly)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1771723	NM_005472.5(KCNE3):c.139C>T (p.Arg47Trp)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1776585	NM_005472.5(KCNE3):c.104C>T (p.Pro35Leu)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1795900	NM_005472.5(KCNE3):c.277C>T (p.His93Tyr)	KCNE3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
KCNE3	Limited	Unknown	Brugada syndrome 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNE3	Orphanet:130	Brugada syndrome
KCNE3	Orphanet:681	Hypokalemic periodic paralysis

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
KCNE3	HGNC:6243	ENSG00000175538	Q9Y6H6	Potassium voltage-gated channel subfamily E member 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNE3	Potassium voltage-gated channel subfamily E member 3	Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.

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)
KCNE3	Ion channel	yes		K_chnl_KCNE, K_chnl_volt-dep_bsu_KCNE3

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
leukocyte	1
monocyte	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNE3	227	broad	marker	nasal cavity epithelium, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNE3	1,467

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNE3	Q9Y6H6	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Phase 3 - rapid repolarisation	1	1142.0×	0.003	KCNE3
Phase 2 - plateau phase	1	761.3×	0.003	KCNE3
Cardiac conduction	1	108.8×	0.012	KCNE3
Muscle contraction	1	77.2×	0.013	KCNE3

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
negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential	1	16852.0×	7e-04	KCNE3
negative regulation of delayed rectifier potassium channel activity	1	2808.7×	0.001	KCNE3
negative regulation of potassium ion export across plasma membrane	1	2407.4×	0.001	KCNE3
intracellular chloride ion homeostasis	1	1685.2×	0.001	KCNE3
membrane repolarization during action potential	1	1685.2×	0.001	KCNE3
membrane repolarization during ventricular cardiac muscle cell action potential	1	1685.2×	0.001	KCNE3
potassium ion export across plasma membrane	1	1053.2×	0.001	KCNE3
ventricular cardiac muscle cell action potential	1	991.3×	0.001	KCNE3
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.001	KCNE3
regulation of heart rate by cardiac conduction	1	374.5×	0.003	KCNE3
sodium ion transport	1	271.8×	0.004	KCNE3

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
KCNE3	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	KCNE3
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)
KCNE3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.