Catecholaminergic polymorphic ventricular tachycardia 3

Summary

Catecholaminergic polymorphic ventricular tachycardia 3 (MONDO:0013529) is a disease caused by TECRL (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TECRL (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	catecholaminergic polymorphic ventricular tachycardia 3
Mondo ID	MONDO:0013529
OMIM	614021
DOID	DOID:0060677
UMLS	C3151463
MedGen	462813
GARD	0015744
Is cancer (heuristic)	no

Also known as: catecholaminergic polymorphic ventricular tachycardia 3 · catecholaminergic polymorphic ventricular tachycardia caused by mutation in TECRL · catecholaminergic polymorphic ventricular tachycardia type 3 · CPVT3 · TECRL catecholaminergic polymorphic ventricular tachycardia · ventricular tachycardia, catecholaminergic polymorphic, 3

Data availability: 21 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

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 3

Related subtypes (6): catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 2, catecholaminergic polymorphic ventricular tachycardia 4, catecholaminergic polymorphic ventricular tachycardia 5, 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

21 retrieved; paginated sample, class counts are floors:

6 conflicting classifications of pathogenicity, 5 pathogenic, 3 likely pathogenic, 2 likely benign, 2 uncertain significance, 1 benign/likely benign, 1 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1750178	NM_001010874.5(TECRL):c.586C>T (p.Arg196Ter)	TECRL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1755289	NM_001010874.5(TECRL):c.675G>A (p.Trp225Ter)	TECRL	Pathogenic	criteria provided, multiple submitters, no conflicts
3255077	NM_001010874.5(TECRL):c.395_408dup (p.Leu137fs)	TECRL	Pathogenic	criteria provided, single submitter
372283	NM_001010874.5(TECRL):c.331+1G>A	TECRL	Pathogenic	criteria provided, single submitter
3805415	NM_001010874.5(TECRL):c.567T>A (p.Cys189Ter)	TECRL	Pathogenic	criteria provided, multiple submitters, no conflicts
814027	NM_001010874.5(TECRL):c.918+3A>G	TECRL	Pathogenic	no assertion criteria provided
1210126	NM_001010874.5(TECRL):c.742_758del (p.Arg248fs)	TECRL	Likely pathogenic	criteria provided, single submitter
2442197	NM_001010874.5(TECRL):c.271_272del (p.Lys91fs)	TECRL	Likely pathogenic	criteria provided, single submitter
372284	NM_001010874.5(TECRL):c.587G>A (p.Arg196Gln)	TECRL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1034365	NM_001010874.5(TECRL):c.172A>G (p.Thr58Ala)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1178321	NM_001010874.5(TECRL):c.454A>G (p.Thr152Ala)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1187774	NM_001010874.5(TECRL):c.33A>T (p.Glu11Asp)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1321522	NM_001010874.5(TECRL):c.893T>C (p.Val298Ala)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1766009	NM_001010874.5(TECRL):c.915T>G (p.Tyr305Ter)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1794643	NM_001010874.5(TECRL):c.1009del (p.Ala337fs)	TECRL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1804999	NM_001010874.5(TECRL):c.55C>T (p.Gln19Ter)	TECRL	Uncertain significance	criteria provided, single submitter
2497301	NM_001010874.5(TECRL):c.236T>C (p.Val79Ala)	TECRL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1217074	NM_001010874.5(TECRL):c.536G>A (p.Arg179His)	TECRL	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1757723	NM_001010874.5(TECRL):c.720T>C (p.Tyr240=)	TECRL	Likely benign	criteria provided, multiple submitters, no conflicts
3766511	NM_001010874.5(TECRL):c.964+15T>A	TECRL	Likely benign	criteria provided, single submitter
710201	NM_001010874.5(TECRL):c.552-13dup	TECRL	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TECRL	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
TECRL	HGNC:27365	ENSG00000205678	Q5HYJ1	Trans-2,3-enoyl-CoA reductase-like	gencc,clinvar

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)
TECRL	Other/Unknown	no		3-oxo-5_a-steroid_4-DH_C, SRD5A/TECR, TECRL_Ubl

Expression context

Cohort genes with no expression data: 0.

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
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TECRL	135	tissue_specific	yes	myocardium, heart right ventricle, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TECRL	814

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TECRL	Q5HYJ1	84.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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 very long-chain fatty acyl-CoAs	1	456.8×	0.006	TECRL
Fatty acyl-CoA biosynthesis	1	439.2×	0.006	TECRL
Fatty acid metabolism	1	131.3×	0.013	TECRL
Metabolism of lipids	1	31.6×	0.040	TECRL
Metabolism	1	11.6×	0.086	TECRL

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
very long-chain fatty acid biosynthetic process	1	1296.3×	0.001	TECRL
sphingolipid metabolic process	1	991.3×	0.001	TECRL

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
TECRL	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	TECRL

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)
TECRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.