Arrhythmogenic right ventricular dysplasia 13

Summary

Arrhythmogenic right ventricular dysplasia 13 (MONDO:0000908) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 925

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arrhythmogenic right ventricular dysplasia 13
Mondo ID	MONDO:0000908
OMIM	615616
DOID	DOID:0110084
UMLS	C3810138
MedGen	816468
GARD	0022844
Is cancer (heuristic)	no

Also known as: arrhythmogenic right ventricular cardiomyopathy 13 · arrhythmogenic right ventricular cardiomyopathy caused by mutation in CTNNA3 · arrhythmogenic right ventricular dysplasia type 13 · arrhythmogenic right ventricular dysplasia, familial, 13 · arrhythmogenic right ventricular dysplasia, familial, type 13 · ARVC13 · ARVD13 · CTNNA3 arrhythmogenic right ventricular cardiomyopathy

Data availability: 925 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › familial cardiomyopathy › familial isolated arrhythmogenic right ventricular dysplasia › arrhythmogenic right ventricular dysplasia 13

Related subtypes (15): arrhythmogenic right ventricular dysplasia 1, arrhythmogenic right ventricular dysplasia 3, arrhythmogenic right ventricular dysplasia 4, arrhythmogenic right ventricular dysplasia 5, arrhythmogenic right ventricular dysplasia 6, catecholaminergic polymorphic ventricular tachycardia 1, arrhythmogenic right ventricular dysplasia 8, arrhythmogenic right ventricular dysplasia 9, arrhythmogenic right ventricular dysplasia 10, arrhythmogenic right ventricular dysplasia 11, arrhythmogenic right ventricular dysplasia 12, familial isolated arrhythmogenic ventricular dysplasia, left dominant form, familial isolated arrhythmogenic ventricular dysplasia, biventricular form, familial isolated arrhythmogenic ventricular dysplasia, right dominant form, arrhythmogenic right ventricular dysplasia, familial, 14

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

600 retrieved; paginated sample, class counts are floors:

358 uncertain significance, 200 likely benign, 15 conflicting classifications of pathogenicity, 14 benign, 10 benign/likely benign, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
100656	NM_013266.4(CTNNA3):c.281T>A (p.Val94Asp)	CTNNA3	Pathogenic	no assertion criteria provided
100657	NM_013266.4(CTNNA3):c.2293TTG[1] (p.Leu766del)	CTNNA3	Pathogenic	no assertion criteria provided
2583173	NM_013266.4(CTNNA3):c.2159+2T>C	CTNNA3	Likely pathogenic	criteria provided, single submitter
1085062	NM_013266.4(CTNNA3):c.1937G>A (p.Arg646His)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1144273	NM_013266.4(CTNNA3):c.1192G>A (p.Val398Ile)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1153884	NM_013266.4(CTNNA3):c.2404G>T (p.Asp802Tyr)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1164628	NM_013266.4(CTNNA3):c.1318G>A (p.Asp440Asn)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1317629	NM_013266.4(CTNNA3):c.1281+4A>G	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1350311	NM_013266.4(CTNNA3):c.770A>G (p.Gln257Arg)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
155780	NM_013266.4(CTNNA3):c.2573T>C (p.Leu858Ser)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180310	NM_013266.4(CTNNA3):c.457G>C (p.Ala153Pro)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2176203	NM_013266.4(CTNNA3):c.1431C>A (p.Asn477Lys)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220976	NM_013266.4(CTNNA3):c.1231A>G (p.Ile411Val)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220977	NM_013266.4(CTNNA3):c.1303A>G (p.Met435Val)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240866	NM_013266.4(CTNNA3):c.1900G>A (p.Glu634Lys)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2640516	NM_013266.4(CTNNA3):c.722T>C (p.Val241Ala)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3226228	NM_013266.4(CTNNA3):c.1803G>T (p.Leu601Phe)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3498309	NM_013266.4(CTNNA3):c.168T>A (p.Ser56Arg)	CTNNA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000115	NC_000010.10:g.(?69366605)(69366817_?)del	CTNNA3	Uncertain significance	criteria provided, single submitter
1000118	NC_000010.10:g.(?68940069)(68979634_?)dup	CTNNA3	Uncertain significance	criteria provided, single submitter
1000643	NM_013266.4(CTNNA3):c.181T>C (p.Ser61Pro)	CTNNA3	Uncertain significance	criteria provided, single submitter
1002294	NM_013266.4(CTNNA3):c.1282G>A (p.Val428Met)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1006536	NM_013266.4(CTNNA3):c.2265+2T>A	CTNNA3	Uncertain significance	criteria provided, single submitter
1006879	NM_013266.4(CTNNA3):c.2066C>T (p.Ala689Val)	CTNNA3	Uncertain significance	criteria provided, single submitter
1009070	NM_013266.4(CTNNA3):c.1774G>T (p.Ala592Ser)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1010241	NM_013266.4(CTNNA3):c.1853A>G (p.His618Arg)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1011424	NM_013266.4(CTNNA3):c.1739C>T (p.Pro580Leu)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014294	NM_013266.4(CTNNA3):c.2589G>T (p.Lys863Asn)	CTNNA3	Uncertain significance	criteria provided, single submitter
1015514	NM_013266.4(CTNNA3):c.674G>A (p.Cys225Tyr)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1016700	NM_013266.4(CTNNA3):c.421A>G (p.Met141Val)	CTNNA3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
CTNNA3	Limited	Autosomal dominant	arrhythmogenic right ventricular dysplasia 13	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNA3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
CTNNA3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
CTNNA3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNNA3	HGNC:2511	ENSG00000183230	Q9UI47	Catenin alpha-3	gencc,clinvar
CTNNA3-AS1	HGNC:58344	ENSG00000273360		CTNNA3 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNA3	Catenin alpha-3	May be involved in formation of stretch-resistant cell-cell adhesion complexes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNNA3	Other/Unknown	no		Alpha_catenin, Vinculin/catenin, Alpha-catenin/vinculin-like_sf
CTNNA3-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	2
heart right ventricle	1
medial globus pallidus	1
male germ line stem cell (sensu Vertebrata) in testis	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNA3	211	broad	marker	corpus callosum, heart right ventricle, medial globus pallidus
CTNNA3-AS1	45		yes	male germ line stem cell (sensu Vertebrata) in testis, corpus callosum, skeletal muscle tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNA3	2,306
CTNNA3-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CTNNA3	Q9UI47	81.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	2407.4×	0.002	CTNNA3
regulation of ventricular cardiac muscle cell action potential	1	1404.3×	0.002	CTNNA3
regulation of heart rate by cardiac conduction	1	374.5×	0.004	CTNNA3
cell-cell adhesion	1	101.5×	0.012	CTNNA3
cell migration	1	61.5×	0.016	CTNNA3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
CTNNA3	0	0
CTNNA3-AS1	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	2	CTNNA3, CTNNA3-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CTNNA3	0	—
CTNNA3-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.