CTNNA3

Summary

CTNNA3 (catenin alpha 3, HGNC:2511) is a protein-coding gene on chromosome 10q21.3, encoding Catenin alpha-3 (Q9UI47). May be involved in formation of stretch-resistant cell-cell adhesion complexes.

This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29119 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arrhythmogenic right ventricular cardiomyopathy (Limited, ClinGen) — +2 more curated relationships
• GWAS associations: 39
• Clinical variants (ClinVar): 1,372 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 6
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_013266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2511
Approved symbol	CTNNA3
Name	catenin alpha 3
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	VR22, MGC26194
Ensembl gene	ENSG00000183230
Ensembl biotype	protein_coding
OMIM	607667
Entrez	29119

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000330298, ENST00000373735, ENST00000433211, ENST00000494580, ENST00000545309, ENST00000682166, ENST00000682505, ENST00000682758, ENST00000682945, ENST00000683272, ENST00000683624, ENST00000683630, ENST00000683771, ENST00000683963, ENST00000684154, ENST00000684489

RefSeq mRNA: 3 — MANE Select: NM_013266 NM_001127384, NM_001291133, NM_013266

CCDS: CCDS7269

Canonical transcript exons

ENST00000433211 — 18 exons

Exon	Start	End
ENSE00001290145	67180317	67180520
ENSE00001293786	66766264	66766416
ENSE00001297434	66520617	66520773
ENSE00001298371	66103157	66103249
ENSE00001300830	66280470	66280621
ENSE00001310737	66621692	66621784
ENSE00001319859	66379152	66379352
ENSE00001324335	67219607	67219870
ENSE00001461453	67696000	67696195
ENSE00001670676	67539503	67539669
ENSE00001721297	65912523	65920617
ENSE00002140709	67606857	67607049
ENSE00002159040	67647415	67647518
ENSE00003644301	66069308	66069489
ENSE00003707410	66775444	66775524
ENSE00003707919	65966612	65966746
ENSE00003711334	65988692	65988797
ENSE00003791256	67521842	67521961

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 96.83.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5424 / max 459.2876, expressed in 228 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109716	1.5924	125
109717	1.4658	188
109713	1.1289	85
109715	0.1357	54
109714	0.1350	49
205880	0.0505	40
205881	0.0179	10
109718	0.0161	10

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.83	gold quality
heart right ventricle	UBERON:0002080	96.55	gold quality
medial globus pallidus	UBERON:0002477	96.02	gold quality
globus pallidus	UBERON:0001875	95.83	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.39	gold quality
biceps brachii	UBERON:0001507	95.17	gold quality
inferior vagus X ganglion	UBERON:0005363	95.04	gold quality
subthalamic nucleus	UBERON:0001906	94.50	gold quality
lateral globus pallidus	UBERON:0002476	94.11	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.63	gold quality
endothelial cell	CL:0000115	91.38	gold quality
pons	UBERON:0000988	91.36	gold quality
spinal cord	UBERON:0002240	90.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.42	gold quality
sural nerve	UBERON:0015488	89.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.96	gold quality
vastus lateralis	UBERON:0001379	88.28	gold quality
substantia nigra pars compacta	UBERON:0001965	88.19	gold quality
ventral tegmental area	UBERON:0002691	87.31	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.22	gold quality
myocardium	UBERON:0002349	85.91	gold quality
quadriceps femoris	UBERON:0001377	85.88	gold quality
superior vestibular nucleus	UBERON:0007227	85.50	gold quality
trigeminal ganglion	UBERON:0001675	84.41	gold quality
skeletal muscle tissue	UBERON:0001134	83.53	gold quality
medulla oblongata	UBERON:0001896	83.28	gold quality
left ventricle myocardium	UBERON:0006566	83.12	gold quality
cardiac ventricle	UBERON:0002082	82.97	gold quality
heart left ventricle	UBERON:0002084	82.56	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	6510.52
E-HCAD-35	yes	6106.45
E-HCAD-30	yes	5531.24
E-HCAD-25	yes	5216.20
E-ANND-3	yes	6.30
E-MTAB-11268	no	4790.50
E-ENAD-17	no	223.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA4, MEF2C

miRNA regulators (miRDB)

310 targeting CTNNA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 37)

• gene localized on chromosome 10q21 and is 1,776 kb in length; mutation screening of all 18 exons of the CTNNA3 gene in a family showing dilated cardiomyopathy (DCM)linkage to the 10q21-q23 locus, however, has not detected any DCM-linked CTNNA3 mutations (PMID:12596047)
• Alpha-T catenin gene has variants which influence Abeta42 and contribute to the previously reported linkage for plasma Abeta42 in late-onset Alzheimer’s disease families. (PMID:14559775)
• We found no association between CTNNA3 and Alzheimer disease in subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. CTNNA3 is unlikely to account for the susceptibility locus on chromosome 10 (PMID:15075440)
• GATA-4 and MEF2C transcription factors transactivate the alphaT-catenin gene CTNNA3 in a tissue-specific manner. (PMID:15302915)
• Dosage compensation of CTNNA3 and p57KIP2 in the placenta shares a conserved regulatory mechanism. (PMID:15533819)
• VR22 or a nearby gene influences susceptibility to Alzheimer’s disease, and the effect is dependent on APOE status (PMID:16199552)
• This is the first study to report evidence of an association between a potentially functional, non-synonymous SNP in VR22 and the risk for Alzheimer’s disease. (PMID:17209133)
• In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression. (PMID:17366617)
• By providing an extra link between the cadherin-catenin complex and intermediate filaments, the binding of alphaT-catenin to plakophilin-2 is proposed to be a means of modulating and strengthening cell-cell adhesion between cardiac muscle cells. (PMID:17535849)
• CTNNA3 may affect late-onset Alzheimer’s disease through a female-specific mechanism independent of the APOE-epsilon4 allele. (PMID:17761686)
• Significant association with late-onset Alzheimer’s disease for 4 SNPs: rs1881747 near DKK1, rs2279420 in ANK3, rs2306402 in CTNNA3, and rs5030882 in CXXC6 in 1,160 cases and 1,389 controls. (PMID:18163421)
• Results suggest that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to toluene diisocyanate-induced induced asthma. (PMID:19187332)
• The risk allele (Y153H) of the preeclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein a-T-catenin (CTNNA3). (PMID:20400461)
• Our comprehensive mutation scanning did not identify any Arrhythmogenic right ventricular cardiomyopathy (ARVC) causing mutations. (PMID:21254927)
• Low alpha catenin is involved in colorectal cancer metastasis. (PMID:21562850)
• Apart from the complexity of its regulation, alterations in both CTNNA3 and LRTMM3 are implicated in human disease. (PMID:21598020)
• A VE-cadherin-PAR3-alpha-catenin complex regulates the Golgi localization and activity of cytosolic phospholipase A(2)alpha in endothelial cells. (PMID:22398721)
• Five genes have been directly disrupted in Tourette Syndrome by independent genomic rearrangements and copy number variations with unique breakpoints. (PMID:22948383)
• GWAS study of diisocyanate asthma demonstrates an association between two closely linked CTNNA3 gene SNPs and diisocyanate asthma. (PMID:22977168)
• Results suggest a causal relationship between CTNNA3 mutations and arrhythmogenic right ventricular cardiomyopathy (PMID:23136403)
• Significant interaction with maternal CMV infection was found for rs7902091 (PSNP x CMV=7.3 x 10-7) in CTNNA3, a gene not previously implicated in schizophrenia. (PMID:23358160)
• CTNNA2 and CTNNA3 are tumor suppressor genes frequently mutated in laryngeal carcinomas. (PMID:24100690)
• These results suggest aberrant Claudin 7, alpha - and beta-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively. (PMID:24358122)
• CTNNA3 is not major contributor or genetic risk factor for childhood asthma but rather influence the disease expression and response to therapy. (PMID:24407380)
• This study demonstrated that the copy number variations of CTNNA3 relate to opioid dependence. (PMID:25345593)
• CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies (PMID:26073756)
• Copy Number Variations in CTNNA3 and RBFOX1 Associate with Pediatric Food Allergy (PMID:26188062)
• Two African-ancestry specific variants were found to be significantly associated with metabolic syndrome S: SNP rs73989312[A] near CA10 that conferred increased risk; and SNP rs77244975[C] in CTNNA3 that conferred protection against this disease. (PMID:26507551)
• Loss of CTNNA3 expression is associated with hepatocellular carcinoma. (PMID:26882563)
• Among the genes replicated across the two samples (permutated p < 0.05 in both of them), CTNNA3 appeared promising. The inorganic cation transmembrane transporter activity pathway (GO:0022890) was associated with antidepressant response in both samples (p = 2.9e-5 and p = 0.001 in the Korean and STAR*D samples, respectively) (PMID:27091189)
• We conducted a meta-analysis of studies involving CHAT, TFAM, and VR22 polymorphisms and Alzheimer disease susceptibility. For TFAM and VR22, no significant association was detected in studied single-nucleotide polymorphisms (SNPs). Rs10997691 and rs7070570 of VR22 are not significantly associated with AD risk. (PMID:27272392)
• The functional investigations might indicate involvement of alpha-T-catenin/CTNNA3 in the biology of peripheral nerve sheath tumors. (PMID:27765635)
• CTNNA3 association with essential tremor. (PMID:27797806)
• Double MYH7 CTTNA3 heterozygotes showed a variable clinical expression of arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy. One carrier of double mutations in CTTNA3 and MYH7 genes did not fulfill the current diagnostic criteria for cardiomyopathy. (PMID:28699631)
• G allele of rs7903491 in CTNNA3 is a risk factor for essential tremor in Chinese population. (PMID:28801652)
• CTNNA3 genetic polymorphism may be a new genetic signal of type 2 diabetes in the Chinese Han population: a case control study. (PMID:34717601)
• Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3. (PMID:37126683)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ctnna3	ENSMUSG00000060843
rattus_norvegicus	Ctnna3	ENSRNOG00000000373
drosophila_melanogaster	alpha-Cat	FBGN0010215
caenorhabditis_elegans		WBGENE00001978

Paralogs (4): VCL (ENSG00000035403), CTNNA1 (ENSG00000044115), CTNNA2 (ENSG00000066032), CTNNAL1 (ENSG00000119326)

Protein

Protein identifiers

Catenin alpha-3 — Q9UI47 (reviewed: Q9UI47)

Alternative names: Alpha T-catenin, Cadherin-associated protein

All UniProt accessions (6): Q9UI47, A0A804HI07, A0A804HIE3, F2Z2R0, Q5SW23, V9GYW4

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in formation of stretch-resistant cell-cell adhesion complexes.

Subunit / interactions. Interacts with CTNNB1. Interacts with PKP2.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Desmosome.

Tissue specificity. Predominantly expressed in heart and testis. Expressed at lower levels in brain, kidney, liver and skeletal muscle.

Disease relevance. Arrhythmogenic right ventricular dysplasia, familial, 13 (ARVD13) [MIM:615616] A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the vinculin/alpha-catenin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UI47-1	1	yes
Q9UI47-2	2

RefSeq proteins (2): NP_001120856, NP_037398* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001033	Alpha_catenin	Family
IPR006077	Vinculin/catenin	Family
IPR036723	Alpha-catenin/vinculin-like_sf	Homologous_superfamily

Pfam: PF01044

UniProt features (14 total): modified residue 5, sequence variant 3, coiled-coil region 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI47-F1	81.65	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 56, 160, 637, 647, 649

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 224 (showing top): GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, KEGG_TIGHT_JUNCTION, chr10q21, TGACCTY_ERR1_Q2, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, EVI1_05, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_VENTRICULAR_CARDIAC_MUSCLE_CELL_ACTION_POTENTIAL, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, AML_Q6, BIOCARTA_CELL2CELL_PATHWAY

GO Biological Process (6): cell migration (GO:0016477), bundle of His cell-Purkinje myocyte adhesion involved in cell communication (GO:0086073), regulation of heart rate by cardiac conduction (GO:0086091), cell-cell adhesion (GO:0098609), regulation of ventricular cardiac muscle cell action potential (GO:0098911), cell adhesion (GO:0007155)

GO Molecular Function (4): beta-catenin binding (GO:0008013), cadherin binding (GO:0045296), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (7): cytoskeleton (GO:0005856), adherens junction (GO:0005912), fascia adherens (GO:0005916), lamellipodium (GO:0030027), desmosome (GO:0030057), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell junction	3
cell motility	1
heterotypic cell-cell adhesion	1
cardiac muscle cell-cardiac muscle cell adhesion	1
bundle of His cell to Purkinje myocyte communication	1
regulation of heart rate	1
cardiac conduction	1
cell adhesion	1
regulation of cardiac muscle cell contraction	1
ventricular cardiac muscle cell action potential	1
regulation of cardiac muscle cell action potential	1
cellular process	1
protein binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
binding	1
intracellular membraneless organelle	1
intercalated disc	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

2154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTNNA3	PKP2	Q99959	976
CTNNA3	LRRTM3	Q86VH5	891
CTNNA3	CTNNB1	P35222	855
CTNNA3	CDH17	Q12864	788
CTNNA3	CALHM1	Q8IU99	755
CTNNA3	CDH1	P12830	713
CTNNA3	DSG2	Q14126	691
CTNNA3	CDH2	P19022	663
CTNNA3	TMEM43	Q9BTV4	659
CTNNA3	JUP	P14923	626
CTNNA3	LEF1	Q9UJU2	612
CTNNA3	DSC2	Q02487	602
CTNNA3	ATP11A	P98196	598
CTNNA3	VCL	P18206	595
CTNNA3	DLG2	Q15700	583

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CTNNA3	CTNNB1	psi-mi:“MI:2364”(proximity)	0.610
gag	CTNNA3	psi-mi:“MI:0915”(physical association)	0.500
gag	RNH1	psi-mi:“MI:0914”(association)	0.460
CTNNA3	PKP3	psi-mi:“MI:0915”(physical association)	0.370
EPS8	CTNNA3	psi-mi:“MI:0915”(physical association)	0.370
CTNNA3	ARVCF	psi-mi:“MI:0914”(association)	0.350
CTNNA3	FYN	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): CTNNB1 (Co-localization), CDH3 (Affinity Capture-MS), CDH12 (Affinity Capture-MS), CDH1 (Affinity Capture-MS), APC (Affinity Capture-MS), CDH24 (Affinity Capture-MS), BLZF1 (Affinity Capture-MS), CDH10 (Affinity Capture-MS), ARVCF (Affinity Capture-MS), PKP4 (Affinity Capture-MS), CDH4 (Affinity Capture-MS), CTNNBIP1 (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), VMA21 (Affinity Capture-MS)

ESM2 similar proteins: A2CEI4, A3KNI7, B7ZC77, E7FBU4, G8JYB2, O35095, O43156, O46037, O75800, O88327, O95273, P0DX19, P26231, P35220, P35221, Q08CY4, Q0V9L1, Q14746, Q2KIZ9, Q2KJ97, Q3MHM6, Q3TVC7, Q4R809, Q59I72, Q5BK06, Q5RC06, Q5RFN4, Q5U4I3, Q65CL1, Q69ZR2, Q6GPP1, Q6NVK9, Q6NY52, Q7T006, Q803M5, Q8BTG3, Q8C3S2, Q8JGR7, Q8K2Z4, Q91V83

Diamond homologs: A4IGI7, B7ZC77, P26231, P26232, P30997, P35220, P35221, P90947, Q04615, Q3MHM6, Q59I72, Q5R416, Q61301, Q65CL1, Q6GLP0, Q9PVF8, Q9UI47, O88327, Q5RC06, Q9UBT7, A0A3B6UES5, O46037, P12003, P18206, P19826, P26234, P85972, Q17162, Q54MH2, Q64727

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
GATA4	“up-regulates quantity by expression”	CTNNA3	“transcriptional regulation”
MEF2C	“up-regulates quantity by expression”	CTNNA3	“transcriptional regulation”
CTNNA3	“up-regulates quantity”	CDH1	relocalization
CTNNA3	“up-regulates quantity”	CTNNB1	relocalization
CTNNA3	“up-regulates quantity”	JUP	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

1372 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	834
Likely benign	382
Benign	93

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
100656	NM_013266.4(CTNNA3):c.281T>A (p.Val94Asp)	Pathogenic
100657	NM_013266.4(CTNNA3):c.2293TTG[1] (p.Leu766del)	Pathogenic
1700649	NM_013266.4(CTNNA3):c.2568del (p.Lys856fs)	Likely pathogenic
2574033	NM_013266.4(CTNNA3):c.160del (p.Arg54fs)	Likely pathogenic
2583173	NM_013266.4(CTNNA3):c.2159+2T>C	Likely pathogenic

SpliceAI

4148 predictions. Top by Δscore:

Variant	Effect	Δscore
10:65966610:A:AC	donor_gain	1.0000
10:65966611:C:CC	donor_gain	1.0000
10:65966611:CAG:C	donor_gain	1.0000
10:65966747:C:CC	acceptor_gain	1.0000
10:65988687:CTCA:C	donor_loss	1.0000
10:65988688:TCACC:T	donor_loss	1.0000
10:65988689:CAC:C	donor_loss	1.0000
10:65988690:A:AC	donor_gain	1.0000
10:65988691:C:CC	donor_gain	1.0000
10:65988793:TGCCC:T	acceptor_gain	1.0000
10:65988794:GCCC:G	acceptor_gain	1.0000
10:65988795:CCC:C	acceptor_gain	1.0000
10:65988795:CCCC:C	acceptor_gain	1.0000
10:65988796:CC:C	acceptor_gain	1.0000
10:65988796:CCC:C	acceptor_gain	1.0000
10:65988797:CC:C	acceptor_gain	1.0000
10:65988798:C:CC	acceptor_gain	1.0000
10:65988799:T:A	acceptor_loss	1.0000
10:66033865:T:TA	donor_gain	1.0000
10:66069303:ATTAC:A	donor_loss	1.0000
10:66069304:TTA:T	donor_loss	1.0000
10:66069305:TAC:T	donor_loss	1.0000
10:66069306:ACCTA:A	donor_loss	1.0000
10:66069485:TTAGC:T	acceptor_gain	1.0000
10:66069486:TAGC:T	acceptor_gain	1.0000
10:66069486:TAGCC:T	acceptor_gain	1.0000
10:66069487:AGCCT:A	acceptor_gain	1.0000
10:66069488:GC:G	acceptor_gain	1.0000
10:66069488:GCCT:G	acceptor_gain	1.0000
10:66069489:CC:C	acceptor_gain	1.0000

AlphaMissense

5912 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:65920476:A:G	W848R	1.000
10:65920476:A:T	W848R	1.000
10:65920474:C:A	W848C	0.999
10:65920474:C:G	W848C	0.999
10:65920475:C:G	W848S	0.999
10:66069387:A:G	W694R	0.999
10:66069387:A:T	W694R	0.999
10:66775454:A:G	L373P	0.999
10:67180339:A:G	L342P	0.999
10:65920587:C:G	A811P	0.998
10:65988754:C:G	A735P	0.998
10:65988790:C:G	G723R	0.998
10:65988790:C:T	G723R	0.998
10:66069353:G:T	A705D	0.998
10:66069407:A:G	L687P	0.998
10:66520628:A:G	L507P	0.998
10:66520662:C:G	A496P	0.998
10:66766415:A:G	L377P	0.998
10:67180348:A:G	L339P	0.998
10:65920598:A:G	L807P	0.997
10:65966676:A:G	L779P	0.997
10:65988789:C:T	G723E	0.997
10:66069313:G:C	F718L	0.997
10:66069313:G:T	F718L	0.997
10:66069315:A:G	F718L	0.997
10:66069323:A:C	M715R	0.997
10:66069354:C:G	A705P	0.997
10:66069370:G:C	N699K	0.997
10:66069370:G:T	N699K	0.997
10:66069385:C:A	W694C	0.997

dbSNP variants (sampled 300 via entrez): RS1000001150 (10:66607587 C>A,T), RS1000001416 (10:66571240 T>C), RS1000003534 (10:66802359 A>G), RS1000004392 (10:66760791 A>C,G), RS1000008329 (10:67698660 T>A,C), RS1000010451 (10:67745498 G>A), RS1000012255 (10:66232973 T>C), RS1000013807 (10:66356956 A>G), RS1000015847 (10:66278868 T>A), RS1000016315 (10:67486333 A>G), RS1000016831 (10:65917543 G>A,C,T), RS1000018322 (10:67617350 T>G), RS1000018889 (10:67189315 C>G,T), RS1000020010 (10:65940642 T>C), RS1000020141 (10:66276453 T>C)

Disease associations

OMIM: gene MIM:607667 | disease phenotypes: MIM:615616, MIM:109800, MIM:192600

GenCC curated gene-disease

Disease	Classification	Inheritance
arrhythmogenic right ventricular dysplasia 13	Limited	Autosomal dominant
congenital heart disease	Disputed Evidence	Unknown

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
arrhythmogenic right ventricular cardiomyopathy	Limited	AD
congenital heart disease	Disputed	UD

Mondo (8): arrhythmogenic right ventricular dysplasia 13 (MONDO:0000908), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), congenital heart disease (MONDO:0005453), dilated cardiomyopathy (MONDO:0005021), urinary bladder cancer (MONDO:0001187), long QT syndrome (MONDO:0002442), familial hypertrophic cardiomyopathy (MONDO:0024573), primary ovarian failure (MONDO:0005387)

Orphanet (6): Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

6 total (7 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0003621	Juvenile onset
HP:0004756	Ventricular tachycardia
HP:0005133	Right ventricular dilatation
HP:0011705	First degree atrioventricular block
HP:0011713	Left bundle branch block
HP:0001644	Dilated cardiomyopathy

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000010_2	Nicotine dependence	6.000000e-06
GCST000330_1	Asthma (toluene diisocyanate-induced)	6.000000e-06
GCST001713_27	Dental caries	4.000000e-06
GCST001762_571	Obesity-related traits	8.000000e-06
GCST001833_1	Schizophrenia (cytomegalovirus infection interaction)	7.000000e-07
GCST002104_4	Bronchopulmonary dysplasia	1.000000e-06
GCST002118_10	Metabolite levels (Pyroglutamine)	5.000000e-08
GCST002162_9	Lung function (FVC)	4.000000e-06
GCST002928_9	Nickel levels	8.000000e-06
GCST003270_2	Psoriatic arthritis	1.000000e-06
GCST003542_208	Night sleep phenotypes	3.000000e-06
GCST003672_12	Docetaxel-induced peripheral neuropathy in metastatic castrate-resistant prostate cancer	9.000000e-06
GCST003762_1	Essential tremor	1.000000e-08
GCST004076_5	Optic disc area	5.000000e-08
GCST004735_35	Epstein-Barr virus copy number in lymphoblastoid cell lines	7.000000e-06
GCST005091_5	Subcutaneous adipose tissue	2.000000e-07
GCST005091_6	Subcutaneous adipose tissue	6.000000e-06
GCST005752_40	Systemic lupus erythematosus	4.000000e-06
GCST007096_55	Pulse pressure	6.000000e-10
GCST007099_13	Systolic blood pressure	8.000000e-06
GCST007324_111	Adventurousness	1.000000e-08
GCST007324_125	Adventurousness	2.000000e-08
GCST007325_12	General risk tolerance (MTAG)	8.000000e-09
GCST007393_7	Mitochondrial DNA copy number	2.000000e-07
GCST007637_46	Diffusing capacity of carbon monoxide	5.000000e-06
GCST008595_143	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST009028_25	Adverse response to drug	8.000000e-07
GCST009391_1893	Metabolite levels	3.000000e-06
GCST009391_636	Metabolite levels	9.000000e-06
GCST009524_202	Household income (MTAG)	6.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0005408	pyroglutamine measurement
EFO:0004312	vital capacity
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0006312	mitochondrial DNA measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009658	adverse effect
EFO:0010414	triacylglycerol 52:2 measurement
EFO:0010503	inosine measurement
EFO:0009695	household income
EFO:0004327	electrocardiography

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10997242	Efficacy	3	antidepressants	Major Depressive Disorder

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1786929	CTNNA3	3	2.25	1	fluticasone propionate;montelukast
rs10997242	CTNNA3	3	0.00	1	antidepressants
rs10997459	CTNNA3, LRRTM3		0.00	0

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	affects methylation, increases expression	2
Aflatoxin B1	increases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
aflatoxin B2	decreases methylation	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	decreases expression	1
Cyanates	increases response to substance	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phenobarbital	decreases expression	1
Phthalic Acids	decreases methylation	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
Palmitic Acid	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1TE	SHETi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

337 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE