TRDN

triadin

Basic information

Region (hg38): 6:123216339-123637189

Links

ENSG00000186439

∙ NCBI:10345 ∙ OMIM:603283 ∙ HGNC:12261 ∙ Uniprot:Q13061 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

catecholaminergic polymorphic ventricular tachycardia 5 (Strong), mode of inheritance: AR
catecholaminergic polymorphic ventricular tachycardia (Supportive), mode of inheritance: AD
catecholaminergic polymorphic ventricular tachycardia 5 (Strong), mode of inheritance: AR
catecholaminergic polymorphic ventricular tachycardia 5 (Definitive), mode of inheritance: AR
familial long QT syndrome (Strong), mode of inheritance: AR
long QT syndrome (Strong), mode of inheritance: AR
catecholaminergic polymorphic ventricular tachycardia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiac arrhythmia syndrome with or without skeletal muscle weakness	AR	Cardiovascular	Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including interventions such as medical treatment with beta-blockers or ICD placement) may allow early and beneficial management, which may decrease morbidity and mortality	Cardiovascular; Musculoskeletal; Neurologic	22422768; 25922419; 30649896

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRDN gene.

Catecholaminergic_polymorphic_ventricular_tachycardia_1 (954 variants)
Cardiovascular_phenotype (516 variants)
not_provided (211 variants)
Catecholaminergic_polymorphic_ventricular_tachycardia_5 (128 variants)
not_specified (84 variants)
TRDN-related_disorder (21 variants)
Catecholaminergic_polymorphic_ventricular_tachycardia (12 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRDN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006073.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			11 clinvar	170 clinvar		181
missense	2 clinvar	3 clinvar	412 clinvar	59 clinvar		476
nonsense	5 clinvar	6 clinvar	21 clinvar			32
start loss	1					1
frameshift	12 clinvar	17 clinvar	21 clinvar			50
splice donor/acceptor (+/-2bp)	2 clinvar	15 clinvar	44 clinvar			61
Total	22	41	509	229	0

Highest pathogenic variant AF is 0.00006237709

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRDN	protein_coding	protein_coding	ENST00000398178	41	420756

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.36e-22	0.0920	124508	2	127	124637	0.000518

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0770	294	290	1.01	0.0000136	4687
Missense in Polyphen		60	59.054	1.016		1102
Synonymous	0.0815	93	94.0	0.989	0.00000487	1180
Loss of Function	1.46	39	50.1	0.778	0.00000242	826

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.00148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000341	0.000334
Finnish	0.00	0.00
European (Non-Finnish)	0.000551	0.000531
Middle Eastern	0.000341	0.000334
South Asian	0.00134	0.00118
Other	0.000356	0.000330

dbNSFP

Source: dbNSFP

Function: FUNCTION: 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. Required for normal organization of the triad junction, where T-tubules and the sarcoplasmic reticulum terminal cisternae are in close contact (By similarity). Required for normal skeletal muscle strength. Plays a role in excitation- contraction coupling in the heart and in regulating the rate of heart beats. {ECO:0000250|UniProtKB:E9Q9K5, ECO:0000269|PubMed:22422768}.;
Disease: DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness (CPVT5) [MIM:615441]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, or sudden death after physical activity or emotional stress. Some patients have muscle weakness. CPVT5 inheritance is autosomal recessive. {ECO:0000269|PubMed:22422768}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.159

Intolerance Scores

loftool: 0.861
rvis_EVS: 1.98
rvis_percentile_EVS: 97.61

Haploinsufficiency Scores

pHI: 0.182
hipred: N
hipred_score: 0.203
ghis: 0.396

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.275

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Trdn
Phenotype: muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: cellular calcium ion homeostasis;muscle contraction;response to bacterium;regulation of cell communication by electrical coupling;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;cytoplasmic microtubule organization;ion transmembrane transport;regulation of release of sequestered calcium ion into cytosol;heart contraction;negative regulation of ryanodine-sensitive calcium-release channel activity;positive regulation of ryanodine-sensitive calcium-release channel activity;regulation of cardiac muscle cell membrane potential;endoplasmic reticulum membrane organization;positive regulation of cell communication by electrical coupling involved in cardiac conduction;regulation of cardiac conduction
Cellular component: endoplasmic reticulum;cytosol;plasma membrane;junctional sarcoplasmic reticulum membrane;integral component of membrane;sarcoplasmic reticulum;junctional membrane complex;sarcoplasmic reticulum membrane;sarcoplasmic reticulum lumen
Molecular function: signaling receptor binding;protein binding;protein binding, bridging;ion channel binding