Catecholaminergic polymorphic ventricular tachycardia 5

Summary

Catecholaminergic polymorphic ventricular tachycardia 5 (MONDO:0014191) is a disease caused by TRDN (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TRDN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 143

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	catecholaminergic polymorphic ventricular tachycardia 5
Mondo ID	MONDO:0014191
OMIM	615441
DOID	DOID:0060679
UMLS	C3809536
MedGen	815866
GARD	0015967
Is cancer (heuristic)	no

Also known as: cardiac arrhythmia syndrome, with or without skeletal muscle weakness · catecholaminergic polymorphic ventricular tachycardia 5 · catecholaminergic polymorphic ventricular tachycardia caused by mutation in TRDN · catecholaminergic polymorphic ventricular tachycardia type 5 · CPVT5 · TRDN catecholaminergic polymorphic ventricular tachycardia · ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness

Data availability: 143 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › catecholaminergic polymorphic ventricular tachycardia › catecholaminergic polymorphic ventricular tachycardia 5

Related subtypes (6): catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 2, catecholaminergic polymorphic ventricular tachycardia 3, catecholaminergic polymorphic ventricular tachycardia 4, long QT syndrome 16, ventricular tachycardia, catecholaminergic polymorphic 6

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

143 retrieved; paginated sample, class counts are floors:

54 uncertain significance, 27 conflicting classifications of pathogenicity, 15 likely benign, 15 benign/likely benign, 11 likely pathogenic, 8 pathogenic/likely pathogenic, 7 benign, 5 pathogenic, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070395	NM_006073.4(TRDN):c.22+29A>G	TRDN	Pathogenic	criteria provided, multiple submitters, no conflicts
1075032	NM_006073.4(TRDN):c.531del (p.Glu178fs)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1427034	NM_006073.4(TRDN):c.541G>T (p.Glu181Ter)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708485	NM_006073.4(TRDN):c.508G>T (p.Gly170Ter)	TRDN	Pathogenic	criteria provided, single submitter
225497	NM_006073.4(TRDN):c.568dup (p.Ile190fs)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2634568	NM_006073.4(TRDN):c.326del (p.Leu109fs)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2732852	NM_006073.4(TRDN):c.483del (p.Val162fs)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449691	NM_006073.4(TRDN):c.438_442del (p.Asp146_Lys147insTer)	TRDN	Pathogenic	criteria provided, multiple submitters, no conflicts
66015	NM_006073.4(TRDN):c.53_56del (p.Asp18fs)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66016	NM_006073.4(TRDN):c.613C>T (p.Gln205Ter)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66017	NM_006073.4(TRDN):c.176C>G (p.Thr59Arg)	TRDN	Pathogenic	no assertion criteria provided
838068	NM_006073.4(TRDN):c.502G>T (p.Glu168Ter)	TRDN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
915308	NM_006073.4(TRDN):c.22+1G>T	TRDN	Pathogenic	criteria provided, multiple submitters, no conflicts
1325231	NM_006073.4(TRDN):c.1050del (p.Glu351fs)	TRDN	Likely pathogenic	criteria provided, single submitter
1517713	NM_006073.4(TRDN):c.391+1G>A	TRDN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2434223	NM_006073.4(TRDN):c.424+1G>T	TRDN	Likely pathogenic	criteria provided, single submitter
2434224	NM_006073.4(TRDN):c.1558G>T (p.Glu520Ter)	TRDN	Likely pathogenic	criteria provided, single submitter
3592999	NM_006073.4(TRDN):c.680_681del (p.Gln227fs)	TRDN	Likely pathogenic	criteria provided, single submitter
3593000	NM_006073.4(TRDN):c.383del (p.Thr128fs)	TRDN	Likely pathogenic	criteria provided, single submitter
3780742	NM_006073.4(TRDN):c.1246+1G>T	TRDN	Likely pathogenic	criteria provided, single submitter
3780743	NM_006073.4(TRDN):c.1784-1G>T	TRDN	Likely pathogenic	criteria provided, single submitter
4077704	NM_006073.4(TRDN):c.224dup (p.Asn75fs)	TRDN	Likely pathogenic	criteria provided, single submitter
4077705	NM_006073.4(TRDN):c.1393A>T (p.Lys465Ter)	TRDN	Likely pathogenic	criteria provided, single submitter
408740	NM_006073.4(TRDN):c.167T>C (p.Leu56Pro)	TRDN	Likely pathogenic	criteria provided, single submitter
1040678	NM_006073.4(TRDN):c.1721-4A>T	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1417266	NM_006073.4(TRDN):c.604G>A (p.Ala202Thr)	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1751076	NM_006073.4(TRDN):c.601_610+45delinsG	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1963630	NM_006073.4(TRDN):c.1672+6T>C	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229345	NM_006073.4(TRDN):c.1367A>G (p.Gln456Arg)	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229347	NM_006073.4(TRDN):c.1193A>T (p.Glu398Val)	TRDN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
TRDN	Definitive	Autosomal recessive	catecholaminergic polymorphic ventricular tachycardia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRDN	Orphanet:101016	Romano-Ward syndrome
TRDN	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia

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
TRDN	HGNC:12261	ENSG00000186439	Q13061	Triadin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRDN	Triadin	Contributes to the regulation of lumenal Ca2+ release via the sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key step in triggering skeletal and heart muscle contraction.

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)
TRDN	Other/Unknown	no		Asp-B-hydro/Triadin_dom, Triadin

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
gastrocnemius	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRDN	182	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRDN	1,799

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRDN	Q13061	47.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Ion homeostasis	1	203.9×	0.007	TRDN
Stimuli-sensing channels	1	135.9×	0.007	TRDN

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
positive regulation of cell communication by electrical coupling involved in cardiac conduction	1	8426.0×	0.001	TRDN
regulation of cell communication by electrical coupling	1	2407.4×	0.001	TRDN
regulation of cardiac muscle cell membrane potential	1	2407.4×	0.001	TRDN
endoplasmic reticulum membrane organization	1	2407.4×	0.001	TRDN
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	1685.2×	0.002	TRDN
heart contraction	1	766.0×	0.002	TRDN
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	674.1×	0.002	TRDN
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.002	TRDN
cytoplasmic microtubule organization	1	343.9×	0.004	TRDN
muscle contraction	1	208.1×	0.006	TRDN
response to bacterium	1	193.7×	0.006	TRDN
establishment of localization in cell	1	160.5×	0.007	TRDN
intracellular calcium ion homeostasis	1	145.3×	0.007	TRDN

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
TRDN	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	TRDN

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)
TRDN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.