TRDN

Chr 6AR

triadin

Also known as: CARDAR, CPVT5, TDN, TRISK

NCBI Gene: 10345ENSG00000186439UniProt: Q13061

This gene encodes an integral membrane protein found in skeletal and cardiac muscle. The encoded protein plays a role in skeletal muscle excitation-contraction coupling as part of the calcium release complex and is required for normal skeletal muscle strength. This protein indirectly links triads and microtubules in skeletal muscle. Mutations in this gene are associated with cardiac arrythmia syndrome and some variants in this gene may be associated with sudden cardiac death. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

Cardiac arrhythmia syndrome, with or without skeletal muscle weaknessMIM #615441
AR
492
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRDN
🧬
Gene-Disease Validity (ClinGen)
catecholaminergic polymorphic ventricular tachycardia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 179 VUS of 492 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.02LOEUF
pLI 0.000
Z-score 1.46
OE 0.78 (0.60–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.08Z-score
OE missense 1.01 (0.92–1.11)
294 obs / 290.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.78 (0.60–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 39 / 50.1Missense obs/exp: 294 / 290.3Syn Z: 0.08

ClinVar Variant Classifications

492 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic17
VUS179
Likely Benign272
Benign9
Conflicting2
13
Pathogenic
17
Likely Pathogenic
179
VUS
272
Likely Benign
9
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
9
0
13
Likely Pathogenic
10
1
6
0
17
VUS
13
119
42
5
179
Likely Benign
0
15
184
73
272
Benign
0
0
9
0
9
Conflicting
—2
Total2713525078492

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRDN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TRDN-related long QT syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Cardiac
G2P ↗
frameshift variant NMD triggering

TRDN-related catecholaminergic polymorphic ventricular tachycardia

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cardiac
G2P ↗
missense variantstop gained NMD triggeringframeshift variant NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TRIADIN; TRDN
MIM #603283 · *

Cardiac arrhythmia syndrome, with or without skeletal muscle weakness

MIM #615441

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TRDN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.
Adler A et al.·Circulation
2020
[Clinical and genetic analysis of a case of Triadin knockout syndrome due to variant of TRDN gene and a literature review].
Li H et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Review
International Triadin Knockout Syndrome Registry.
Clemens DJ et al.·Circ Genom Precis Med
2019
Genetics, manifestations, and management of catecholaminergic polymorphic ventricular tachycardia.
Desai S et al.·Curr Opin Cardiol
2025Review
Generation of a Triadin KnockOut Syndrome Zebrafish Model.
Vecchi VM et al.·Int J Mol Sci
2021Functional
Phenotype-guided whole genome analysis in a patient with genetically elusive long QT syndrome yields a novel TRDN-encoded triadin pathogenetic substrate for triadin knockout syndrome and reveals a novel primate-specific cardiac TRDN transcript.
Clemens DJ et al.·Heart Rhythm
2020Case report
Novel cases of pediatric sudden cardiac death secondary to TRDN mutations presenting as long QT syndrome at rest and catecholaminergic polymorphic ventricular tachycardia during exercise: The TRDN arrhythmia syndrome.
Rabbani B et al.·Am J Med Genet A
2021Cohort
A novel homozygous mutation in the TRDN gene causes a severe form of pediatric malignant ventricular arrhythmia.
Rossi D et al.·Heart Rhythm
2020Case report
BASIC AND CLINICAL INSIGHTS IN CATECHOLAMINERGIC (FAMILIAL) POLYMORPHIC VENTRICULAR TACHYCARDIA.
Márquez MF et al.·Rev Invest Clin
2019Review
Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia.
Wleklinski MJ et al.·J Physiol
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools