Brugada syndrome 2
diseaseOn this page
Also known as BRGDA2Brugada syndrome caused by mutation in GPD1LBrugada syndrome type 2GPD1L Brugada syndrome
Summary
Brugada syndrome 2 (MONDO:0012728) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 36
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Brugada syndrome 2 |
| Mondo ID | MONDO:0012728 |
| MeSH | C567087 |
| OMIM | 611777 |
| DOID | DOID:0110219 |
| UMLS | C2673193 |
| MedGen | 382031 |
| GARD | 0015526 |
| Is cancer (heuristic) | no |
Also known as: BRGDA2 · Brugada syndrome 2 · Brugada syndrome caused by mutation in GPD1L · Brugada syndrome type 2 · GPD1L Brugada syndrome
Data availability: 36 ClinVar variants · 2 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 2
Related subtypes (8): Brugada syndrome 1, Brugada syndrome 3, 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
36 retrieved; paginated sample, class counts are floors:
17 uncertain significance, 9 conflicting classifications of pathogenicity, 7 benign/likely benign, 3 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1041106 | NM_015141.4(GPD1L):c.619-9C>A | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1056227 | NM_015141.4(GPD1L):c.376del (p.Glu126fs) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 180369 | NM_015141.4(GPD1L):c.520G>A (p.Glu174Lys) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 463286 | NM_015141.4(GPD1L):c.467A>G (p.Asn156Ser) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 644362 | NM_015141.4(GPD1L):c.838G>A (p.Ala280Thr) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 786 | NM_015141.4(GPD1L):c.839C>T (p.Ala280Val) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 787 | NM_015141.4(GPD1L):c.247G>A (p.Glu83Lys) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 788 | NM_015141.4(GPD1L):c.370A>G (p.Ile124Val) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 789 | NM_015141.4(GPD1L):c.817C>T (p.Arg273Cys) | GPD1L | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1047243 | NM_015141.4(GPD1L):c.416G>A (p.Arg139His) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1326864 | NM_015141.4(GPD1L):c.914CTG[1] (p.Ala306del) | GPD1L | Uncertain significance | criteria provided, single submitter |
| 1423143 | NM_015141.4(GPD1L):c.878T>C (p.Met293Thr) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1496581 | NM_015141.4(GPD1L):c.158C>G (p.Thr53Arg) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1515725 | NM_015141.4(GPD1L):c.853-2A>G | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 191446 | NM_015141.4(GPD1L):c.415C>T (p.Arg139Cys) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 218714 | NM_015141.4(GPD1L):c.977C>A (p.Ala326Glu) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 410225 | NM_015141.4(GPD1L):c.997G>A (p.Glu333Lys) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 452285 | NM_015141.4(GPD1L):c.505G>A (p.Gly169Ser) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 487599 | NM_015141.4(GPD1L):c.775G>A (p.Gly259Arg) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 519421 | NM_015141.4(GPD1L):c.905C>T (p.Pro302Leu) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 560688 | NM_015141.4(GPD1L):c.257A>G (p.Gln86Arg) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 571418 | NM_015141.4(GPD1L):c.560A>G (p.Asn187Ser) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 656217 | NM_015141.4(GPD1L):c.658C>T (p.Arg220Cys) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 809441 | NM_015141.4(GPD1L):c.505+2T>G | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 843122 | NM_015141.4(GPD1L):c.818G>A (p.Arg273His) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 849031 | NM_015141.4(GPD1L):c.482A>G (p.Glu161Gly) | GPD1L | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1245688 | NM_015141.4(GPD1L):c.367-10A>T | GPD1L | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 1250797 | NM_015141.4(GPD1L):c.367-11C>A | GPD1L | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 137491 | NM_015141.4(GPD1L):c.981G>A (p.Val327=) | GPD1L | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 190760 | NM_015141.4(GPD1L):c.81T>C (p.Asn27=) | GPD1L | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 1 · 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 |
|---|---|---|---|---|
| GPD1L | Limited | Unknown | Brugada syndrome 2 | 3 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GPD1L | Orphanet:130 | Brugada syndrome |
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 |
|---|---|---|---|---|---|
| GPD1L | HGNC:28956 | ENSG00000152642 | Q8N335 | Glycerol-3-phosphate dehydrogenase 1-like protein | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GPD1L | Glycerol-3-phosphate dehydrogenase 1-like protein | Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium c… |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GPD1L | Other/Unknown | no | G3P_DH_NAD-dep_C, G3P_DH_NAD-dep, 6-PGluconate_DH-like_C_sf |
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 |
|---|---|
| biceps brachii | 1 |
| heart right ventricle | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GPD1L | 297 | ubiquitous | marker | biceps brachii, heart right ventricle, skeletal muscle tissue of biceps brachii |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GPD1L | 2,618 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| GPD1L | Q8N335 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. 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 |
|---|---|---|---|---|
| Synthesis of PA | 1 | 292.8× | 0.003 | GPD1L |
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 |
|---|---|---|---|---|
| glycerol-3-phosphate catabolic process | 1 | 8426.0× | 9e-04 | GPD1L |
| regulation of ventricular cardiac muscle cell membrane depolarization | 1 | 2808.7× | 0.001 | GPD1L |
| NAD+ metabolic process | 1 | 1872.4× | 0.001 | GPD1L |
| ventricular cardiac muscle cell action potential | 1 | 991.3× | 0.002 | GPD1L |
| positive regulation of sodium ion transport | 1 | 842.6× | 0.002 | GPD1L |
| positive regulation of protein localization to cell surface | 1 | 766.0× | 0.002 | GPD1L |
| regulation of heart rate | 1 | 468.1× | 0.002 | GPD1L |
| carbohydrate metabolic process | 1 | 135.9× | 0.007 | GPD1L |
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 |
|---|---|---|
| GPD1L | 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | GPD1L |
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) |
|---|---|---|
| GPD1L | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: GPD1L