Ventricular septal defect

Summary

Ventricular septal defect (MONDO:0002070) is a disease (an umbrella term covering 5 Mondo subtypes) with 23 cohort genes (134 GWAS associations across 1 studies) and 46 clinical trials. Top therapeutic interventions include enalapril, thiamine ion, and albuterol.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 23
• GWAS associations: 134
• ClinVar variants: 36
• Clinical trials: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ventricular septal defect
Mondo ID	MONDO:0002070
MeSH	D006345
OMIM	614429
Orphanet	1480
DOID	DOID:1657
ICD-10-CM	Q21.0
ICD-11	668140715
NCIT	C84506
SNOMED CT	30288003
UMLS	C0018818
MedGen	42366
Is cancer (heuristic)	no

Also known as: heart septal defects, ventricular · interventricular communication · interventricular septal defect · ventricular septal defect · ventricular septal defect (disease) · ventricular septal defects · VSD

Data availability: 36 ClinVar variants · 134 GWAS associations (1 study) · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › heart septal defect › ventricular septal defect

Related subtypes (2): atrial septal defect, familial atrioventricular septal defect

Subtypes (5): ventricular septal defect 1, ventricular septal defect 2, ventricular septal defect 3, double outlet right ventricle, anterior deviation infundibular septum

Genetics & variants

GWAS landscape

134 GWAS associations across 1 studies. Top hits map to 56 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs79112841	1e-18	MUC3A	?
rs200547048	3e-18	ANKRD36C	?
rs201829271	4e-18	ANKRD36	?
chr1:12907457	5e-18		?
chr17:60512662	5e-18		?
rs62074774	4e-17	NPEPPSP1	?
rs9380481	2e-16	ANKS1A	?
rs2686894	2e-16	SCGB1C1, BET1L	?
rs200791776	3e-16	MUC16	?
rs28523287	2e-15	FRG1BP, FRG1BP	?
rs4689585	2e-15	GRPEL1	?
rs28462372	2e-15	CCDC125	?
rs2256589	3e-15	IGHM	?
rs7125677	5e-15	GRM5P1, GRM5P1	?
rs77306665	7e-15	PABPC3	?
rs594178	8e-15	KMT2C	?
rs8006	1e-14	MRPS21	?
rs1080995	2e-14	NDUFA6-DT, CYP2D6	?
rs1747958	2e-14	PDE4DIP	?
rs72924126	2e-14	ESRRA	?
rs71443637	3e-14	PRR4, PRH1, TAS2R43, TAS2R14	?
rs34652473	5e-14	IGHV1-3	?
rs62039223	5e-14	ARHGAP23P1	?
rs7595595	5e-14	WDPCP	?
rs2974835	6e-14	CACNA1H	?
rs1041992	1e-13	CEACAM4	?
rs4317614	1e-13	CPSF1	?
rs2341893	1e-13	MAP9, MAP9-AS1	?
rs199626069	1e-13	MUC6	?
rs2153463	3e-13	ACP6	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90246230	Jin L	2022	80	0	Integrated genomic analysis identifies novel low-frequency cis-regulatory variant rs2279658 associated with VSD risk in Chinese children.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	7
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	7

Functional consequences

Consequence	Count
intron_variant	30
missense_variant	7
synonymous_variant	6
unknown	3
3_prime_UTR_variant	2
non_coding_transcript_exon_variant	1
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs79112841	7	100952961	C>A	0.05	synonymous_variant	MUC3A	1e-18	Tier 4: intronic/intergenic
rs200547048	2	95944983	C>G,T	0.05	intron_variant	ANKRD36C	3e-18	Tier 4: intronic/intergenic
rs201829271	2	97167662	C>T	0.05	intron_variant	ANKRD36	4e-18	Tier 4: intronic/intergenic
chr1:12907457							5e-18	Tier 4: intronic/intergenic
chr17:60512662							5e-18	Tier 4: intronic/intergenic
rs62074774	17	38123993	A>C,G,T	0.05	intron_variant	NPEPPSP1	4e-17	Tier 4: intronic/intergenic
rs9380481	6	35009886	C>A,G,T	0.05	intron_variant	ANKS1A	2e-16	Tier 4: intronic/intergenic
rs2686894	11	193865	T>C,G	0.05	missense_variant	SCGB1C1, BET1L	2e-16	Tier 1: coding
rs200791776	19	8914928	A>G	0.05	synonymous_variant	MUC16	3e-16	Tier 4: intronic/intergenic
rs28523287	20	30397823	G>A,T	0.05	intron_variant	FRG1BP, FRG1BP	2e-15	Tier 4: intronic/intergenic
rs4689585	4	7062550	C>A,T	0.05	intron_variant	GRPEL1	2e-15	Tier 4: intronic/intergenic
rs28462372	5	69314182	A>C,G,T	0.05	intron_variant	CCDC125	2e-15	Tier 4: intronic/intergenic
rs2256589	14	105852108	C>A,G,T	0.05	intron_variant	IGHM	3e-15	Tier 4: intronic/intergenic
rs7125677	11	49615864	A>G	0.05	intron_variant	GRM5P1, GRM5P1	5e-15	Tier 4: intronic/intergenic
rs77306665	13	25097260	C>T	0.05	synonymous_variant	PABPC3	7e-15	Tier 4: intronic/intergenic
rs594178	7	152248130	T>A,C	0.05	synonymous_variant	KMT2C	8e-15	Tier 4: intronic/intergenic
rs8006	1	150308367	G>A,C	0.05	3_prime_UTR_variant	MRPS21	1e-14	Tier 2: splice/UTR
rs1080995	22	42130578	C>A,G,T	0.05	intron_variant	NDUFA6-DT, CYP2D6	2e-14	Tier 4: intronic/intergenic
rs1747958	1	149005097	A>G	0.05	missense_variant	PDE4DIP	2e-14	Tier 1: coding
rs72924126	11	64315780	T>C	0.05	synonymous_variant	ESRRA	2e-14	Tier 4: intronic/intergenic
rs71443637	12	11091595	T>C	0.05	missense_variant	PRR4, PRH1, TAS2R43, TAS2R14	3e-14	Tier 1: coding
rs34652473	14	106005446	C>A,G,T	0.05	intron_variant	IGHV1-3	5e-14	Tier 4: intronic/intergenic
rs62039223	16	33928317	T>C		non_coding_transcript_exon_variant	ARHGAP23P1	5e-14	Tier 4: intronic/intergenic
rs7595595	2	63153674	G>A,T	0.05	intron_variant	WDPCP	5e-14	Tier 4: intronic/intergenic
rs2974835	16	1205030	A>G,T	0.05	intron_variant	CACNA1H	6e-14	Tier 4: intronic/intergenic
rs1041992	19	41625899	C>A,T	0.05	synonymous_variant	CEACAM4	1e-13	Tier 4: intronic/intergenic
rs4317614	8	144398573	G>A,C,T	0.05	missense_variant	CPSF1	1e-13	Tier 1: coding
rs2341893	4	155355281	C>A,G,T	0.05	intron_variant	MAP9, MAP9-AS1	1e-13	Tier 4: intronic/intergenic
rs199626069	11	1016800	G>A,C	0.05	missense_variant	MUC6	1e-13	Tier 1: coding
rs2153463	1	147652507	T>A,C,G	0.05	missense_variant	ACP6	3e-13	Tier 1: coding

ClinVar germline variants

36 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 7 conflicting classifications of pathogenicity, 6 pathogenic, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
268041	46;XY;t(5;7)(q35;q33)dn		Pathogenic	criteria provided, single submitter
638670	Single allele	APBA2	Pathogenic	no assertion criteria provided
13978	NM_004333.6(BRAF):c.1502A>G (p.Glu501Gly)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1472670	NM_001012426.2(FOXP4):c.1540G>A (p.Ala514Thr)	FOXP4	Pathogenic	criteria provided, multiple submitters, no conflicts
638672	GRCh37/hg19 22q11.22-11.23(chr22:22971867-23643138)	IGLL5	Pathogenic	no assertion criteria provided
495227	NM_181486.4(TBX5):c.1221C>G (p.Tyr407Ter)	TBX5	Pathogenic	criteria provided, single submitter
30053	NM_000459.5(TEK):c.2690A>G (p.Tyr897Cys)	TEK	Pathogenic	criteria provided, multiple submitters, no conflicts
242897	NM_001271874.2(AAR2):c.520G>A (p.Val174Met)	AAR2	Likely pathogenic	no assertion criteria provided
208506	GRCh37/hg19 14q24.2-q24.3(chr14:73152115..77698582)	ANGEL1	Likely pathogenic	no assertion criteria provided
374061	NM_001451.3(FOXF1):c.280A>T (p.Asn94Tyr)	FOXF1	Likely pathogenic	criteria provided, single submitter
374121	NM_004586.3(RPS6KA3):c.533C>G (p.Ala178Gly)	RPS6KA3	Likely pathogenic	criteria provided, single submitter
978557	NM_000089.4(COL1A2):c.280-7T>C	COL1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
617640	NM_001110556.2(FLNA):c.3934C>T (p.Arg1312Cys)	FLNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872918	NM_001384.5(DPH2):c.922C>T (p.Gln308Ter)	LOC126805726	Conflicting classifications of pathogenicity	no assertion criteria provided
872919	NM_001384.5(DPH2):c.601C>T (p.Arg201Cys)	LOC126805726	Conflicting classifications of pathogenicity	no assertion criteria provided
638278	NM_001042424.3(NSD2):c.3295G>A (p.Glu1099Lys)	NSD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374051	NM_003072.5(SMARCA4):c.1358C>T (p.Thr453Ile)	SMARCA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
816865	NM_003072.5(SMARCA4):c.2900G>A (p.Arg967His)	SMARCA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267820	46;XY;t(16;20)(q11.2;q13.2)dn		Uncertain significance	criteria provided, single submitter
267835	46;XX;der(6)t(6;13)(q23.3;q22)inv(6)(p21.3q15);der(13)t(6;13)dn		Uncertain significance	criteria provided, single submitter
267862	46;XY;t(1;3)(p22;q21)dn		Uncertain significance	criteria provided, single submitter
267864	46;XY;t(2;13)(p25.2;q31.3)dn		Uncertain significance	criteria provided, single submitter
267920	46;XY;t(6;20)(p12;q13.1)dn		Uncertain significance	criteria provided, single submitter
267988	46;XY;inv(9)(p24q12)		Uncertain significance	criteria provided, single submitter
638671	GRCh37/hg19 15q26.3(chr15:100923767-101626187)	ALDH1A3	Uncertain significance	no assertion criteria provided
917519	NM_030632.3(ASXL3):c.1354G>A (p.Glu452Lys)	ASXL3	Uncertain significance	no assertion criteria provided
2570675	NM_015089.4(CUL9):c.7237C>T (p.Arg2413Trp)	CUL9	Uncertain significance	criteria provided, single submitter
2570677	NM_015089.4(CUL9):c.2732C>T (p.Pro911Leu)	CUL9	Uncertain significance	criteria provided, single submitter
978558	NM_001999.4(FBN2):c.7663A>G (p.Thr2555Ala)	FBN2	Uncertain significance	criteria provided, single submitter
523310	GRCh37/hg19 14q24.3(chr14:76105695-76107636)	FLVCR2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 57 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS6KA3	Orphanet:192	Coffin-Lowry syndrome
RPS6KA3	Orphanet:276630	Symptomatic form of Coffin-Lowry syndrome in female carriers
RPS6KA3	Orphanet:777	X-linked non-syndromic intellectual disability
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
TEK	Orphanet:1059	Blue rubber bleb nevus
TEK	Orphanet:2451	Mucocutaneous venous malformations
TEK	Orphanet:714806	Multifocal sporadic venous malformation
TEK	Orphanet:98976	Congenital glaucoma
NSD2	Orphanet:280	Wolf-Hirschhorn syndrome
FLVCR2	Orphanet:221126	Fowler vasculopathy
COL1A2	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A2	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A2	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A2	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A2	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A2	Orphanet:230851	Cardiac-valvular Ehlers-Danlos syndrome
COL1A2	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A2	Orphanet:314029	High bone mass osteogenesis imperfecta
ASXL3	Orphanet:352577	Bainbridge-Ropers syndrome
HUWE1	Orphanet:528084	Non-specific syndromic intellectual disability
FBN2	Orphanet:115	Congenital contractural arachnodactyly
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction
FOXF1	Orphanet:210122	Congenital alveolar capillary dysplasia
ALDH1A3	Orphanet:35612	Nanophthalmos

Cohort genes → proteins

23 cohort genes, 23 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	23

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS6KA3	HGNC:10432	ENSG00000177189	P51812	Ribosomal protein S6 kinase alpha-3	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	clinvar
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	clinvar
NSD2	HGNC:12766	ENSG00000109685	O96028	Histone-lysine N-methyltransferase NSD2	clinvar
AAR2	HGNC:15886	ENSG00000131043	Q9Y312	Protein AAR2 homolog	clinvar
CUL9	HGNC:15982	ENSG00000112659	Q8IWT3	Cullin-9	clinvar
ANGEL1	HGNC:19961	ENSG00000013523	Q9UNK9	RNA 2’,3’-cyclic phosphatase ANGEL1	clinvar
FLVCR2	HGNC:20105	ENSG00000119686	Q9UPI3	Choline/ethanolamine transporter FLVCR2	clinvar
FOXP4	HGNC:20842	ENSG00000137166	Q8IVH2	Forkhead box protein P4	clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	clinvar
WAPL	HGNC:23293	ENSG00000062650	Q7Z5K2	Wings apart-like protein homolog	clinvar
ASXL3	HGNC:29357	ENSG00000141431	Q9C0F0	Putative Polycomb group protein ASXL3	clinvar
HUWE1	HGNC:30892	ENSG00000086758	Q7Z6Z7	E3 ubiquitin-protein ligase HUWE1	clinvar
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
FOXF1	HGNC:3809	ENSG00000103241	Q12946	Forkhead box protein F1	clinvar
IGLL5	HGNC:38476	ENSG00000254709	B9A064	Immunoglobulin lambda-like polypeptide 5	clinvar
ALDH1A3	HGNC:409	ENSG00000184254	P47895	Retinaldehyde dehydrogenase 3	clinvar
APBA2	HGNC:579	ENSG00000034053	Q99767	Amyloid-beta A4 precursor protein-binding family A member 2	clinvar
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	clinvar
MYCN	HGNC:7559	ENSG00000134323	P04198	N-myc proto-oncogene protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS6KA3	Ribosomal protein S6 kinase alpha-3	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation thr…
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
TEK	Angiopoietin-1 receptor	Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskelet…
NSD2	Histone-lysine N-methyltransferase NSD2	Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at ‘Lys-36’ (H3K36me2).
AAR2	Protein AAR2 homolog	Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
CUL9	Cullin-9	Core component of a Cul9-RING ubiquitin-protein ligase complex composed of CUL9 and RBX1.
ANGEL1	RNA 2’,3’-cyclic phosphatase ANGEL1	Exhibits weak RNA 2’,3’-cyclic phosphatase, catalyzing the hydrolysis of RNA molecules with a 2’,3’-cyclic phosphate at the 3’ end to produce RNA with a linear 3’-phosphate group.
FLVCR2	Choline/ethanolamine transporter FLVCR2	Choline uniporter that specifically mediates choline uptake at the blood-brain-barrier.
FOXP4	Forkhead box protein P4	Transcriptional repressor that represses lung-specific expression.
COL1A2	Collagen alpha-2(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
WAPL	Wings apart-like protein homolog	Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin.
ASXL3	Putative Polycomb group protein ASXL3	Putative Polycomb group (PcG) protein.
HUWE1	E3 ubiquitin-protein ligase HUWE1	E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins.
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
FOXF1	Forkhead box protein F1	Probable transcription activator for a number of lung-specific genes.
ALDH1A3	Retinaldehyde dehydrogenase 3	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
APBA2	Amyloid-beta A4 precursor protein-binding family A member 2	Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery.
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.
MYCN	N-myc proto-oncogene protein	Positively regulates the transcription of MYCNOS in neuroblastoma cells.

Protein-family classification

Druggable: 9 · Difficult: 7 · Unknown: 7 · Druggable fraction: 0.39

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
Kinase	3	3.6×	0.206
Transcription factor	6	2.1×	0.206
Phosphatase	1	3.6×	0.412
Transporter	1	3.4×	0.412
Antibody/Immunoglobulin	2	2.5×	0.412
Enzyme (other)	2	1.0×	0.777
Scaffold/PPI	1	0.8×	0.853
Other/Unknown	7	0.6×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS6KA3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TEK	Kinase	yes	2.7.10.1	Prot_kinase_dom, EGF, Ser-Thr/Tyr_kinase_cat_dom
NSD2	Transcription factor	no	2.1.1.356	PWWP_dom, SET_dom, Znf_RING
AAR2	Other/Unknown	no		AAR2, Aar2_N, AAR2_C
CUL9	Transcription factor	no		Znf_RING, IBR_dom, APC_su10/DOC_dom
ANGEL1	Phosphatase	yes		Endo/exonuclease/phosphatase, Endo/exonu/phosph_ase_sf, CCR4/nocturin_mRNA_transcr
FLVCR2	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
FOXP4	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily
WAPL	Other/Unknown	no		ARM-like, WAPL_dom, ARM-type_fold
ASXL3	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
HUWE1	Enzyme (other)	yes	2.3.2.26	HECT_dom, WWE_dom, UBA-like_sf
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
FOXF1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
IGLL5	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig-like_dom
ALDH1A3	Enzyme (other)	yes	1.2.1.5	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
APBA2	Scaffold/PPI	no		PDZ, PTB/PI_dom, PH-like_dom_sf
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
MYCN	Transcription factor	no		Tscrpt_reg_Myc, bHLH_dom, Tscrpt_reg_Myc_N

Expression context

Cohort genes with no expression data: 0.

22 cohort genes 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)	23
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	4
buccal mucosa cell	3
secondary oocyte	3
cartilage tissue	2
ganglionic eminence	2
right lung	2
ventricular zone	2
left testis	2
right testis	2
stromal cell of endometrium	2
colonic mucosa	1
mucosa of sigmoid colon	1
calcaneal tendon	1
colonic epithelium	1
cervix squamous epithelium	1
cardiac muscle of right atrium	1
tendon of biceps brachii	1
diaphragm	1
visceral pleura	1
lower esophagus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS6KA3	285	ubiquitous	marker	cartilage tissue, mucosa of sigmoid colon, colonic mucosa
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
TEK	223	broad	marker	right lung, diaphragm, visceral pleura
NSD2	281	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
AAR2	262	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, smooth muscle tissue
CUL9	275	ubiquitous	marker	right testis, left testis, right frontal lobe
ANGEL1	279	ubiquitous	marker	right testis, left testis, body of pancreas
FLVCR2	211	ubiquitous	marker	secondary oocyte, tibial nerve, monocyte
FOXP4	235	ubiquitous	marker	kidney epithelium, pylorus, body of stomach
COL1A2	295	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip
WAPL	298	ubiquitous	marker	secondary oocyte, oocyte, sperm
ASXL3	205	broad	marker	buccal mucosa cell, secondary oocyte, cortical plate
HUWE1	300	ubiquitous	marker	skin of leg, skin of abdomen, right lobe of thyroid gland
FBN2	194	ubiquitous	marker	cartilage tissue, placenta, adrenal tissue
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
FOXF1	202	broad	marker	muscle layer of sigmoid colon, mucosa of stomach, right lung
IGLL5	117	tissue_specific	marker	duodenum, rectum, bone marrow cell
ALDH1A3	244	ubiquitous	marker	palpebral conjunctiva, pigmented layer of retina, parietal pleura
APBA2	131	ubiquitous	marker	superior frontal gyrus, right hemisphere of cerebellum, cerebellum
LRP1	293	ubiquitous	marker	stromal cell of endometrium, descending thoracic aorta, ascending aorta
MYCN	223	broad	yes	ventricular zone, cortical plate, embryo

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138
BRAF	7,394
MYCN	7,345
HUWE1	5,793
FLNA	5,321
ALDH1A3	4,146
NSD2	3,530
AAR2	3,006
TEK	2,762
RPS6KA3	2,713

Intra-cohort edges

A	B	Sources
FOXF1	LRP1	intact
HUWE1	MYCN	biogrid_interaction
SMARCA4	TBX5	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
SMARCA4	P51532	31
FLNA	P21333	26
NSD2	O96028	22
HUWE1	Q7Z6Z7	19
TEK	Q02763	17
RPS6KA3	P51812	15
ALDH1A3	P47895	10
LRP1	Q07954	7
FLVCR2	Q9UPI3	5
COL1A2	P08123	5
TBX5	Q99593	4
CUL9	Q8IWT3	4
WAPL	Q7Z5K2	3
MYCN	P04198	2
AAR2	Q9Y312	1
FOXP4	Q8IVH2	1
IGLL5	B9A064	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANGEL1	Q9UNK9	70.65
APBA2	Q99767	59.74
FOXF1	Q12946	59.41
ASXL3	Q9C0F0	39.70
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 190. Enrichment computed across 23 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
GP1b-IX-V activation signalling	2	112.0×	0.026	COL1A2, FLNA
Defective VWF binding to collagen type I	1	223.9×	0.098	COL1A2
Signaling by MRAS-complex mutants	1	167.9×	0.098	BRAF
Enhanced cleavage of VWF variant by ADAMTS13	1	167.9×	0.098	COL1A2
Defective VWF cleavage by ADAMTS13 variant	1	167.9×	0.098	COL1A2
Signalling to p38 via RIT and RIN	1	134.3×	0.098	BRAF
Formation of lateral plate mesoderm	1	134.3×	0.098	FOXF1
Negative feedback regulation of MAPK pathway	1	112.0×	0.098	BRAF
ARMS-mediated activation	1	96.0×	0.098	BRAF
CREB phosphorylation	1	96.0×	0.098	RPS6KA3
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	96.0×	0.098	COL1A2
Defective binding of VWF variant to GPIb:IX:V	1	96.0×	0.098	COL1A2
Prolonged ERK activation events	1	84.0×	0.098	BRAF
RSK activation	1	84.0×	0.098	RPS6KA3
SHOC2 M1731 mutant abolishes MRAS complex function	1	84.0×	0.098	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	84.0×	0.098	BRAF
OAS antiviral response	1	74.6×	0.098	FLNA
Cohesin Loading onto Chromatin	1	67.2×	0.098	WAPL
Signaling by FGFR3	1	67.2×	0.098	BRAF
Establishment of Sister Chromatid Cohesion	1	61.1×	0.098	WAPL
Signaling by FGFR4	1	61.1×	0.098	BRAF
Regulation of CDH11 gene transcription	1	61.1×	0.098	FOXF1
Regulation of CDH1 mRNA translation by microRNAs	1	61.1×	0.098	MYCN
Frs2-mediated activation	1	56.0×	0.098	BRAF
Scavenging of heme from plasma	1	51.7×	0.098	LRP1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	51.7×	0.098	RPS6KA3
Gastrin-CREB signalling pathway via PKC and MAPK	1	51.7×	0.098	RPS6KA3
Signaling by FGFR1	1	48.0×	0.098	BRAF
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	44.8×	0.098	TBX5
Anchoring fibril formation	1	44.8×	0.098	COL1A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic eye morphogenesis	2	133.2×	0.019	FBN2, ALDH1A3
endocardial cushion development	2	122.1×	0.019	TBX5, FOXF1
lung development	3	25.9×	0.019	TBX5, FOXF1, MYCN
animal organ morphogenesis	3	25.0×	0.019	BRAF, ASXL3, FOXF1
face development	2	69.8×	0.025	BRAF, ALDH1A3
detection of wounding	1	732.7×	0.027	FOXF1
nucleus accumbens development	1	732.7×	0.027	ALDH1A3
embryonic ectodermal digestive tract morphogenesis	1	732.7×	0.027	FOXF1
right lung morphogenesis	1	732.7×	0.027	FOXF1
cell migration involved in coronary vasculogenesis	1	732.7×	0.027	TBX5
protein heterotrimerization	1	732.7×	0.027	COL1A2
positive regulation of cardiac conduction	1	732.7×	0.027	TBX5
positive regulation of transcytosis	1	732.7×	0.027	LRP1
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	732.7×	0.027	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	732.7×	0.027	FLNA
positive regulation of mesenchymal cell proliferation	2	52.3×	0.027	FOXF1, MYCN
negative regulation of endothelial cell apoptotic process	2	43.1×	0.027	BRAF, TEK
embryonic limb morphogenesis	2	34.9×	0.028	TBX5, FBN2
optic cup morphogenesis involved in camera-type eye development	1	366.4×	0.028	ALDH1A3
cardiac left ventricle formation	1	366.4×	0.028	TBX5
atrial septum secundum morphogenesis	1	366.4×	0.028	NSD2
positive regulation of lipid transport	1	366.4×	0.028	LRP1
negative regulation of chromatin binding	1	366.4×	0.028	WAPL
negative regulation of sister chromatid cohesion	1	366.4×	0.028	WAPL
lateral mesodermal cell differentiation	1	366.4×	0.028	FOXF1
atrioventricular node cell fate commitment	1	366.4×	0.028	TBX5
bundle of His cell to Purkinje myocyte communication by electrical coupling	1	366.4×	0.028	TBX5
positive regulation of cell communication by electrical coupling involved in cardiac conduction	1	366.4×	0.028	TBX5
positive regulation of reverse cholesterol transport	1	366.4×	0.028	LRP1
regulation of endothelial cell apoptotic process	1	366.4×	0.028	TEK

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ketamine, Sodium Chloride.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 7 · Undrugged: 16

Druggability breadth: 14 of 23 evidence-associated genes (61%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPS6KA3	FEDRATINIB
BRAF	VEMURAFENIB
TEK	CETIRIZINE
NSD2	VENETOCLAX

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRAF	48	4
RPS6KA3	46	4
TEK	46	4
NSD2	8	4
SMARCA4	2	2
WAPL	1	2
FLNA	1	2
TBX5	0	0
AAR2	0	0
CUL9	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	BRAF, RPS6KA3, TEK
PALBOCICLIB	4	RPS6KA3
ENTRECTINIB	4	RPS6KA3
BOSUTINIB	4	RPS6KA3, TEK
GILTERITINIB	4	RPS6KA3
BRIGATINIB	4	RPS6KA3
UPADACITINIB	4	RPS6KA3
NINTEDANIB	4	RPS6KA3, TEK
SUNITINIB	4	RPS6KA3
QUIZARTINIB	4	RPS6KA3, TEK
MIDOSTAURIN	4	RPS6KA3, TEK
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
SORAFENIB	4	BRAF, TEK
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, TEK
INFIGRATINIB	4	BRAF, TEK
REGORAFENIB	4	BRAF, TEK
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, TEK
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, TEK
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
RPS6KA3	770	Binding:768, Functional:1, ADMET:1
TEK	707	Binding:701, Functional:4, ADMET:2
NSD2	264	Binding:256, Functional:8
SMARCA4	230	Binding:207, ADMET:12, Functional:11
ALDH1A3	55	Binding:55
MYCN	11	Binding:11
FLNA	7	Binding:7
WAPL	6	Binding:6
COL1A2	4	Functional:4
HUWE1	4	Binding:3, Functional:1
CUL9	2	Binding:2
TBX5	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPS6KA3	2.7.11.1	non-specific serine/threonine protein kinase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TEK	2.7.10.1	receptor protein-tyrosine kinase
NSD2	2.1.1.356, 2.1.1.357, 2.1.1.359	[histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine36 N-dimethyltransferase, [histone H3]-lysine36 N-trimethyltransferase
HUWE1	2.3.2.26	HECT-type E3 ubiquitin transferase
ALDH1A3	1.2.1.5	aldehyde dehydrogenase [NAD(P)+]

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RPS6KA3	770
BRAF	1,442
SMARCA4	230
TEK	707
NSD2	264

Pharmacogenomics

Cohort genes with a PharmGKB record: 23; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	BRAF, RPS6KA3, TEK
PALBOCICLIB	4	RPS6KA3
ENTRECTINIB	4	RPS6KA3
BOSUTINIB	4	RPS6KA3, TEK
GILTERITINIB	4	RPS6KA3
BRIGATINIB	4	RPS6KA3
UPADACITINIB	4	RPS6KA3
NINTEDANIB	4	RPS6KA3, TEK
SUNITINIB	4	RPS6KA3
QUIZARTINIB	4	RPS6KA3, TEK
MIDOSTAURIN	4	RPS6KA3, TEK
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
SORAFENIB	4	BRAF, TEK
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, TEK
INFIGRATINIB	4	BRAF, TEK
REGORAFENIB	4	BRAF, TEK
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, TEK
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, TEK
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	RPS6KA3, BRAF, TEK, NSD2
B	Phased (≥1) drug, not yet approved	3	SMARCA4, WAPL, FLNA
C	Druggable family + PDB, no drug	4	FLVCR2, HUWE1, IGLL5, ALDH1A3
D	Druggable family + AlphaFold only, no drug	1	ANGEL1
E	Difficult family or no structure, no drug	11	TBX5, AAR2, CUL9, FOXP4, COL1A2, ASXL3, FBN2, FOXF1, APBA2, LRP1 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TBX5	1	—
AAR2	0	—
CUL9	2	—
ANGEL1	0	—
FLVCR2	0	—
FOXP4	0	—
COL1A2	4	—
ASXL3	0	—
HUWE1	4	—
FBN2	0	—
FOXF1	0	—
IGLL5	0	—
ALDH1A3	55	—
APBA2	0	—
LRP1	0	—
MYCN	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 46.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	33
PHASE2	4
PHASE3	3
PHASE4	2
PHASE1	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02914652	PHASE4	COMPLETED	The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Patients Born With Ventricular Septum Defects.
NCT05688670	PHASE4	COMPLETED	Regional Anesthesia Following Pediatric Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00113698	PHASE3	TERMINATED	Angiotensin Converting Enzyme Inhibition in Children With Mitral Regurgitation
NCT05253209	PHASE3	TERMINATED	A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
NCT04017975	PHASE2	ACTIVE_NOT_RECRUITING	Optical Tissue Identification for Myocardial Architecture
NCT00199771	PHASE2	COMPLETED	Hypertonic Saline Dextran in Pediatric Cardiac Surgery
NCT00556361	PHASE2	COMPLETED	Use of Ketamine Prior to Cardiopulmonary Bypass in Children
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT01120964	PHASE1/PHASE2	COMPLETED	Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery : Revised Protocol
NCT01825369	PHASE1	WITHDRAWN	Aberrations in Carnitine Homeostasis in Congenital Heart Disease With Increased Pulmonary Blood Flow
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT06298344	EARLY_PHASE1	COMPLETED	The Role of Thiamine After Transcatheter Closure in Children With Left-to-Right Shunt Congenital Heart Disease
NCT06492473	Not specified	RECRUITING	Clinical Evaluation Of Ventricular Septal Defect (VSD) In Children at Sohag Univesity Hospital
NCT06676345	Not specified	RECRUITING	Mechanical Complications of Acute Myocardial Infarction: a Multicenter Prospective Study
NCT06822400	Not specified	RECRUITING	Investigation of Tetralogy of Fallot in Neonates
NCT07040579	Not specified	NOT_YET_RECRUITING	Bioabsorbable Occluder for Outlet VSD: Safety and Aortic Valve Effects
NCT07267884	Not specified	NOT_YET_RECRUITING	IABP for MI-VSD Patients in SCAI SHOCK Stage B
NCT07375602	Not specified	RECRUITING	A Multimodal AI Prediction Model for Complications After Transcatheter Closure of Perimembranous VSD in Children
NCT07393243	Not specified	NOT_YET_RECRUITING	Bypass Clear Priming VSD Cardiopulmonary Bypass Circuit Reduce Bypass Associated Inflammation?
NCT00005190	Not specified	COMPLETED	Reproduction and Survival After Cardiac Defect Repair
NCT00005322	Not specified	COMPLETED	Molecular Genetic Epidemiology of Endocardial Cushion Defects - SCOR in Pediatric Cardiovascular Disease
NCT00005546	Not specified	COMPLETED	Molecular Genetic Epidemiology of Three Cardiac Defects -SCOR in Pediatric Cardiovascular Disease
NCT00006272	Not specified	UNKNOWN	Study of Energy Expenditure in Infants With Ventricular Septal Defects
NCT00173186	Not specified	UNKNOWN	Aortic Regurgitation After Surgical Repair of Outlet-Type Ventricular Septal Defect
NCT00229827	Not specified	TERMINATED	Optimal Timing for Repair of Left to Right Shunt Lesions
NCT00390702	Not specified	COMPLETED	Safety and Effectiveness of the Nit-Occlud® Lê VSD Spiral Coil System
NCT00583505	Not specified	NO_LONGER_AVAILABLE	Emergency/Compassionate Use - Membranous VSD Occluder
NCT00583791	Not specified	COMPLETED	Closure of Muscular Ventricular Septal Defects With The AMPLATZER™ Muscular VSD Occluder
NCT00590382	Not specified	APPROVED_FOR_MARKETING	Emergency/Compassionate Use - Muscular VSD Occluder
NCT00647387	Not specified	COMPLETED	Closure of Muscular Ventricular Septal Defects (VSDs) With the AMPLATZER Muscular VSD (MuVSD) Occluder - Post Approval Study
NCT00890799	Not specified	COMPLETED	Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects
NCT01313832	Not specified	COMPLETED	The Effect of Remote Ischemic Preconditioning on the Ischemic Reperfusion Injury in Infants With Ventricular Septal Defect and Pulmonary Hypertension
NCT01480908	Not specified	COMPLETED	Right Bundle Branch Block After Surgical Closure of Ventricular Septal Defect
NCT02138435	Not specified	COMPLETED	Longterm Outcome After Ventricular Septal Defect Closure
NCT02361008	Not specified	COMPLETED	A Randomized Controlled Trial:Treatments on Infundibular Ventricular Septal Defect
NCT02552485	Not specified	COMPLETED	Evaluation of Latent Pulmonary Arterial Hypertension in Congenital Shunt Lesions
NCT03127748	Not specified	UNKNOWN	Cardiac Function After Transcatheter VSD Closure
NCT03684161	Not specified	COMPLETED	Cardiopulmonary Function in Adults Born With a Ventricular Septal Defect
NCT03941691	Not specified	UNKNOWN	A Trial to Evaluate the Safety and Efficacy of a Fully Degradable Ventricular Septal Defect (VSD) Closure

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ENALAPRIL	4	3
THIAMINE ION	4	2
ALBUTEROL	4	1
FLUORESCEIN SODIUM	4	1
L-CITRULLINE	3	2
PLASMALYTE A	3	1