Tetralogy of fallot

disease

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Also known as Fallot tetralogyTOFventricular septal defect with pulmonary stenosis or atresia, dextraposition of aorta, and hypertrophy of right ventricle

Summary

Tetralogy of fallot (MONDO:0008542) is a disease caused by variants in NKX2-5, KDR, and ZFPM2, with 28 cohort genes and 74 clinical trials. The dominant Reactome pathway is Cardiogenesis (5 cohort genes). Top therapeutic interventions include dexmedetomidine, calcium gluconate, and eplerenone.

At a glance

Prevalence: Unknown (Worldwide) [Orphanet-validated]
Causal genes: NKX2-5 (GenCC Definitive), KDR (GenCC Strong), ZFPM2 (GenCC Strong)
Cohort genes: 28
ClinVar variants: 391
Phenotypes (HPO): 12
Clinical trials: 74

Clinical features

Epidemiology

Prevalence records

23 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000	34	Worldwide	Validated
Prevalence at birth	1-5 / 10 000	29.3	Europe	Validated
Prevalence at birth	1-5 / 10 000	39.3	Austria	Validated
Prevalence at birth	1-5 / 10 000	40.8	Belgium	Validated
Prevalence at birth	1-5 / 10 000	11.4	Croatia	Validated
Prevalence at birth	1-5 / 10 000	39.7	Denmark	Validated
Prevalence at birth	1-5 / 10 000	13.8	France	Validated
Prevalence at birth	1-5 / 10 000	11.9	Germany	Validated
Prevalence at birth	1-5 / 10 000	34.3	Hungary	Validated
Prevalence at birth	1-5 / 10 000	14.5	Ireland	Validated
Prevalence at birth	1-5 / 10 000	26.8	Italy	Validated
Prevalence at birth	1-5 / 10 000	48.2	Malta	Validated
Prevalence at birth	1-5 / 10 000	29.2	Netherlands	Validated
Prevalence at birth	1-5 / 10 000	31.1	Norway	Validated
Prevalence at birth	1-5 / 10 000	16.2	Poland	Validated
Prevalence at birth	1-5 / 10 000	23.7	Portugal	Validated
Prevalence at birth	6-9 / 10 000	63	Taiwan, Province of China	Validated
Prevalence at birth	1-5 / 10 000	11.9	Spain	Validated
Prevalence at birth	1-5 / 10 000	25.1	Switzerland	Validated
Prevalence at birth	1-5 / 10 000	32	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000337	Broad forehead	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0005105	Abnormal nasal morphology	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000268	Dolichocephaly	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0001636	Tetralogy of Fallot	Frequent (30-79%)
HP:0004467	Preauricular pit	Frequent (30-79%)
HP:0009891	Underdeveloped supraorbital ridges	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	tetralogy of fallot
Mondo ID	MONDO:0008542
MeSH	D013771
OMIM	187500
Orphanet	3303
DOID	DOID:6419
ICD-10-CM	Q21.3
ICD-11	90973426
NCIT	C84505
SNOMED CT	86299006
UMLS	C0039685
MedGen	21498
GARD	0002245
MedDRA	10016193
NORD	1764
Is cancer (heuristic)	no

Also known as: Fallot tetralogy · tetralogy of fallot · TOF · ventricular septal defect with pulmonary stenosis or atresia, dextraposition of aorta, and hypertrophy of right ventricle

Data availability: 391 ClinVar variants · 12 GenCC gene-disease records · 10 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › tetralogy of fallot

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

391 retrieved; paginated sample, class counts are floors:

149 uncertain significance, 116 conflicting classifications of pathogenicity, 37 likely benign, 30 pathogenic, 27 benign/likely benign, 13 likely pathogenic, 11 benign, 7 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
625669	GRCh37/hg19 8p23.3-23.1(chr8:194617-7787444)	AGPAT5	Pathogenic	criteria provided, single submitter
625634	GRCh37/hg19 8p23.1(chr8:8403375-11805960)	BLK	Pathogenic	criteria provided, single submitter
1707635	NM_001458.5(FLNC):c.1453C>T (p.Gln485Ter)	FLNC	Pathogenic	criteria provided, single submitter
4819649	NM_005257.6(GATA6):c.1020C>G (p.Tyr340Ter)	GATA6	Pathogenic	criteria provided, single submitter
977802	NM_005257.6(GATA6):c.23G>A (p.Trp8Ter)	GATA6	Pathogenic	criteria provided, single submitter
3777042	NM_012259.3(HEY2):c.171G>C (p.Glu57Asp)	HEY2	Pathogenic	criteria provided, single submitter
1032929	NM_000214.3(JAG1):c.3001_3002dup (p.Cys1002fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
177941	NM_000214.3(JAG1):c.2122_2125del (p.Gln708fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
213529	NM_000214.3(JAG1):c.439+1G>A	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
213538	NM_000214.3(JAG1):c.2230C>T (p.Arg744Ter)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
234320	NM_000214.3(JAG1):c.703C>T (p.Arg235Ter)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
234321	NM_000214.3(JAG1):c.1485_1486del (p.Cys496fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
2717767	NM_000214.3(JAG1):c.2999dup (p.Ala1001fs)	JAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280608	NM_000214.3(JAG1):c.311del (p.Gly104fs)	JAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289599	NM_000214.3(JAG1):c.1395+3A>G	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
3382532	NM_000214.3(JAG1):c.1794_1797del (p.Cys599fs)	JAG1	Pathogenic	criteria provided, single submitter
3382687	NM_000214.3(JAG1):c.2472C>A (p.Cys824Ter)	JAG1	Pathogenic	criteria provided, single submitter
598457	NM_000214.3(JAG1):c.1452_1453del (p.Cys484_Glu485delinsTer)	JAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7619	NM_000214.3(JAG1):c.550C>T (p.Arg184Cys)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
7620	NM_000214.3(JAG1):c.551G>A (p.Arg184His)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
7621	NM_000214.3(JAG1):c.2096_2100del (p.Gly699fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
849005	NM_000214.3(JAG1):c.2172_2173dup (p.Asp725fs)	JAG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
930690	NM_000214.3(JAG1):c.228del (p.Val77fs)	JAG1	Pathogenic	criteria provided, single submitter
587690	NC_012920.1(MT-CO1):m.6941del	MT-CO1	Pathogenic	no assertion criteria provided
590294	NC_012920.1(MT-CO1):m.6902del	MT-CO1	Pathogenic	no assertion criteria provided
590295	NC_012920.1(MT-CO1):m.6927del	MT-CO1	Pathogenic	no assertion criteria provided
590893	NC_012920.1(MT-CO1):m.5954del	MT-CO1	Pathogenic	no assertion criteria provided
587691	NC_012920.1(MT-CO2):m.7639del	MT-CO2	Pathogenic	no assertion criteria provided
599026	NC_012920.1(MT-CO3):m.9429_9430insCCC	MT-CO3	Pathogenic	no assertion criteria provided
599027	NC_012920.1(MT-CO3):m.9443_9444insTTT	MT-CO3	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 89 · Orphanet: 89 · 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
NKX2-5	Definitive	Autosomal dominant	tetralogy of fallot	17
KDR	Strong	Autosomal dominant	tetralogy of fallot	3
ZFPM2	Strong	Autosomal dominant	tetralogy of fallot	8
GATA6	Moderate	Autosomal dominant	tetralogy of fallot	16
FLT4	Supportive	Autosomal dominant	tetralogy of fallot	10
GATA4	Supportive	Autosomal dominant	tetralogy of fallot	15
GATA5	Supportive	Autosomal dominant	tetralogy of fallot	7
JAG1	Supportive	Autosomal dominant	tetralogy of fallot	8
POPDC1	Limited	Autosomal recessive	tetralogy of fallot	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZFPM2	Orphanet:2140	Congenital diaphragmatic hernia
ZFPM2	Orphanet:251510	46,XY partial gonadal dysgenesis
ZFPM2	Orphanet:3303	Tetralogy of Fallot
NKX2-5	Orphanet:101351	Familial isolated congenital asplenia
NKX2-5	Orphanet:1479	Atrial septal defect-atrioventricular conduction defects syndrome
NKX2-5	Orphanet:1627	Deletion 5q35 syndrome
NKX2-5	Orphanet:2248	Hypoplastic left heart syndrome
NKX2-5	Orphanet:3303	Tetralogy of Fallot
NKX2-5	Orphanet:334	Hereditary atrial fibrillation
NKX2-5	Orphanet:402075	Familial bicuspid aortic valve
NKX2-5	Orphanet:871	Hereditary progressive cardiac conduction defect
NKX2-5	Orphanet:95712	Thyroid ectopia
NKX2-5	Orphanet:95713	Athyreosis
NKX2-5	Orphanet:99103	Atrial septal defect, ostium secundum type
GATA4	Orphanet:251071	8p23.1 microdeletion syndrome
GATA4	Orphanet:251510	46,XY partial gonadal dysgenesis
GATA4	Orphanet:3303	Tetralogy of Fallot
GATA4	Orphanet:334	Hereditary atrial fibrillation
GATA4	Orphanet:576232	Partial atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
GATA4	Orphanet:99103	Atrial septal defect, ostium secundum type
GATA6	Orphanet:2140	Congenital diaphragmatic hernia
GATA6	Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
GATA6	Orphanet:3303	Tetralogy of Fallot
GATA6	Orphanet:334	Hereditary atrial fibrillation
GATA6	Orphanet:665044	Common arterial trunk with aortic dominance
GATA6	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
GATA6	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA6	Orphanet:99103	Atrial septal defect, ostium secundum type
JAG1	Orphanet:261600	Alagille syndrome due to 20p12 microdeletion
JAG1	Orphanet:261619	Alagille syndrome due to a JAG1 point mutation
JAG1	Orphanet:3303	Tetralogy of Fallot
KDR	Orphanet:3303	Tetralogy of Fallot
POPDC1	Orphanet:476084	BVES-related limb-girdle muscular dystrophy
GATA5	Orphanet:3303	Tetralogy of Fallot
GATA5	Orphanet:334	Hereditary atrial fibrillation
GATA5	Orphanet:402075	Familial bicuspid aortic valve
FLT4	Orphanet:3303	Tetralogy of Fallot
FLT4	Orphanet:79452	Milroy disease
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
TBX1	Orphanet:1727	22q11.2 duplication syndrome
TBX1	Orphanet:3303	Tetralogy of Fallot
TBX1	Orphanet:567	22q11.2 deletion syndrome
TBX1	Orphanet:665044	Common arterial trunk with aortic dominance
TBX1	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
TBX1	Orphanet:685017	Combined immunodeficiency due to TBX1 deficiency
CERS1	Orphanet:424027	Progressive myoclonic epilepsy type 8

Cohort genes → proteins

28 cohort genes, 28 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	28

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZFPM2	HGNC:16700	ENSG00000169946	Q8WW38	Zinc finger protein ZFPM2	gencc,clinvar
NKX2-5	HGNC:2488	ENSG00000183072	P52952	Homeobox protein Nkx-2.5	gencc,clinvar
GATA4	HGNC:4173	ENSG00000136574	P43694	Transcription factor GATA-4	gencc,clinvar
GATA6	HGNC:4174	ENSG00000141448	Q92908	Transcription factor GATA-6	gencc,clinvar
JAG1	HGNC:6188	ENSG00000101384	P78504	Protein jagged-1	gencc,clinvar
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	gencc,clinvar
POPDC1	HGNC:1152	ENSG00000112276	Q8NE79	Popeye domain-containing protein 1	gencc
GATA5	HGNC:15802	ENSG00000130700	Q9BWX5	Transcription factor GATA-5	gencc
FLT4	HGNC:3767	ENSG00000037280	P35916	Vascular endothelial growth factor receptor 3	gencc
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	clinvar
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	clinvar
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	clinvar
TBX1	HGNC:11592	ENSG00000184058	O43435	T-box transcription factor TBX1	clinvar
CERS1	HGNC:14253	ENSG00000223802	P27544	Ceramide synthase 1	clinvar
CRELD1	HGNC:14630	ENSG00000163703	Q96HD1	Protein disulfide isomerase CRELD1	clinvar
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	clinvar
AGPAT5	HGNC:20886	ENSG00000155189	Q9NUQ2	1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
LIMS3	HGNC:30047	ENSG00000256977	P0CW19	LIM and senescent cell antigen-like-containing domain protein 3	clinvar
EPHB4	HGNC:3395	ENSG00000196411	P54760	Ephrin type-B receptor 4	clinvar
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	clinvar
HEY2	HGNC:4881	ENSG00000135547	Q9UBP5	Hairy/enhancer-of-split related with YRPW motif protein 2	clinvar
IRX4	HGNC:6129	ENSG00000113430	P78413	Iroquois-class homeodomain protein IRX-4	clinvar
MT-CO1	HGNC:7419	ENSG00000198804	P00395	Cytochrome c oxidase subunit 1	clinvar
MT-CO2	HGNC:7421	ENSG00000198712	P00403	Cytochrome c oxidase subunit 2	clinvar
MT-CO3	HGNC:7422	ENSG00000198938	P00414	Cytochrome c oxidase subunit 3	clinvar
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	clinvar
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZFPM2	Zinc finger protein ZFPM2	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.
NKX2-5	Homeobox protein Nkx-2.5	Transcription factor required for the development of the heart and the spleen.
GATA4	Transcription factor GATA-4	Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function.
GATA6	Transcription factor GATA-6	Transcriptional activator.
JAG1	Protein jagged-1	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
POPDC1	Popeye domain-containing protein 1	Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity.
GATA5	Transcription factor GATA-5	Transcription factor required during cardiovascular development.
FLT4	Vascular endothelial growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic developm…
ROBO1	Roundabout homolog 1	Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuro…
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.
TBX1	T-box transcription factor TBX1	Transcription factor that plays a key role in cardiovascular development by promoting pharyngeal arch segmentation during embryonic development.
CERS1	Ceramide synthase 1	Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA).
CRELD1	Protein disulfide isomerase CRELD1	Protein disulfide isomerase.
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
AGPAT5	1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon	Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
EPHB4	Ephrin type-B receptor 4	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
HEY2	Hairy/enhancer-of-split related with YRPW motif protein 2	Downstream effector of Notch signaling which may be required for cardiovascular development.
IRX4	Iroquois-class homeodomain protein IRX-4	Likely to be an important mediator of ventricular differentiation during cardiac development.
MT-CO1	Cytochrome c oxidase subunit 1	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CO2	Cytochrome c oxidase subunit 2	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
MT-CO3	Cytochrome c oxidase subunit 3	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…

Protein-family classification

Druggable: 10 · Difficult: 10 · Unknown: 8 · Druggable fraction: 0.36

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	5	5.0×	0.013
Transcription factor	9	2.6×	0.013
Antibody/Immunoglobulin	2	2.1×	0.498
Enzyme (other)	3	1.3×	0.626
Scaffold/PPI	1	0.6×	0.974
Other/Unknown	8	0.5×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZFPM2	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
NKX2-5	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
GATA4	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA
GATA6	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA
JAG1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, VWF_dom
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
POPDC1	Other/Unknown	no		POPDC1-3, RmlC-like_jellyroll, cNMP-bd_dom_sf
GATA5	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA
FLT4	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
TBX1	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
CERS1	Enzyme (other)	yes	2.3.1.299	TLC-dom, Lag1/Lac1-like
CRELD1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
AGPAT5	Enzyme (other)	yes	2.3.1.51	Plipid/glycerol_acylTrfase, Acyltransf_C
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
LIMS3	Transcription factor	no		Znf_LIM, PINCH-1-4-like
EPHB4	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
HEY2	Transcription factor	no		Orange_dom, bHLH_dom, HLH_DNA-bd_sf
IRX4	Transcription factor	no		HD, Iroquois_homeo, KN_HD
MT-CO1	Enzyme (other)	yes	7.1.1.9	Cyt_C_Oxase_1, Cyt_c_Oxase_su1_BS, Cyt_c_oxase-like_su1_dom
MT-CO2	Other/Unknown	no		Copper_CuA, CcO_II-like_C, Cupredoxin
MT-CO3	Other/Unknown	no		Cyt_c_oxidase-like_su3, Cyt_c_oxidase_su3_a-hlx, Cyt_c/ubiquinol_Oxase_su3
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom

Expression context

Cohort genes with no expression data: 0.

24 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)	28
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	4
germinal epithelium of ovary	3
hindlimb stylopod muscle	3
rectum	3
skeletal muscle tissue of biceps brachii	2
apex of heart	2
right atrium auricular region	2
jejunal mucosa	2
parietal pleura	2
tibialis anterior	2
male germ line stem cell (sensu Vertebrata) in testis	2
gastrocnemius	2
colonic epithelium	2
stromal cell of endometrium	2
granulocyte	2
biceps brachii	1
cardiac atrium	1
duodenum	1
heart left ventricle	1
blood vessel layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZFPM2	239	ubiquitous	marker	skeletal muscle tissue of biceps brachii, germinal epithelium of ovary, biceps brachii
NKX2-5	98	broad	yes	apex of heart, right atrium auricular region, cardiac atrium
GATA4	85	broad	marker	right atrium auricular region, heart left ventricle, duodenum
GATA6	204	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, jejunal mucosa
JAG1	297	ubiquitous	marker	upper leg skin, skin of hip, blood vessel layer
KDR	267	broad	marker	germinal epithelium of ovary, lower lobe of lung, parietal pleura
POPDC1	211	ubiquitous	yes	left ventricle myocardium, tibialis anterior, cardiac muscle of right atrium
GATA5	106	broad	yes	ileal mucosa, left uterine tube, jejunal mucosa
FLT4	172	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium
TBX1	220	broad	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
CERS1	177	broad	yes	C1 segment of cervical spinal cord, right frontal lobe, spinal cord
CRELD1	134	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ACTN2	226	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle
AGPAT5	137	ubiquitous	marker	corpus callosum, ventricular zone, cortical plate
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
LIMS3	129		marker	endometrium, stromal cell of endometrium, ascending aorta
EPHB4	282	ubiquitous	marker	olfactory bulb, type B pancreatic cell, body of uterus
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
HEY2	247	broad	marker	popliteal artery, tibial artery, heart right ventricle
IRX4	93	broad	marker	skin of abdomen, apex of heart, cervix squamous epithelium
MT-CO1	134	ubiquitous	marker	granulocyte, stromal cell of endometrium, rectum
MT-CO2	134	ubiquitous	marker	granulocyte, rectum, transverse colon
MT-CO3	134	ubiquitous	marker	zone of skin, endocervix, rectum
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH1	7,411
GATA4	4,994
KDR	4,960
JAG1	4,405
RET	4,203
MT-CO1	3,547
NIPBL	3,278
FLNC	3,174
BMP7	3,134
MT-CO2	3,057

Intra-cohort edges

A	B	Sources
CRELD1	GATA4	string_interaction
CRELD1	NKX2-5	string_interaction
EPHB4	HEY2	string_interaction
FLT4	KDR	intact, string_interaction
GATA4	HEY2	string_interaction
GATA4	IRX4	string_interaction
GATA4	NKX2-5	biogrid_interaction, intact, string_interaction
GATA4	POPDC1	string_interaction
GATA4	ZFPM2	biogrid_interaction, string_interaction
GATA5	NKX2-5	string_interaction
GATA5	ZFPM2	string_interaction
HEY2	IRX4	string_interaction
HEY2	JAG1	string_interaction
HEY2	NKX2-5	string_interaction
HEY2	NOTCH1	string_interaction
IRX4	NKX2-5	string_interaction
JAG1	NOTCH1	intact, string_interaction
MT-CO1	MT-CO2	string_interaction
MT-CO1	MT-CO3	string_interaction
MT-CO2	MT-CO3	intact, string_interaction
NKX2-5	TBX1	string_interaction
NKX2-5	ZFPM2	string_interaction

Structural data

PDB: 17 · AlphaFold-only: 11 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDR	P35968	54
RET	P07949	34
NOTCH1	P46531	29
EPHB4	P54760	23
ACTN2	P35609	16
FLNC	Q14315	14
ROBO1	Q9Y6N7	12
JAG1	P78504	7
NKX2-5	P52952	4
BMP7	P18075	4
MT-CO2	P00403	4
GATA4	P43694	3
NIPBL	Q6KC79	3
MT-CO1	P00395	3
MT-CO3	P00414	3
FLT4	P35916	2
TBX1	O43435	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGPAT5	Q9NUQ2	94.23
CERS1	P27544	88.95
BLK	P51451	81.89
CRELD1	Q96HD1	81.68
POPDC1	Q8NE79	76.08
LIMS3	P0CW19	73.65
HEY2	Q9UBP5	65.56
GATA5	Q9BWX5	59.91
IRX4	P78413	54.03
GATA6	Q92908	53.48
ZFPM2	Q8WW38	51.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 135. Enrichment computed across 28 evidence-associated genes (24 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 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cardiogenesis	5	88.1×	3e-07	NKX2-5, GATA4, GATA6, TBX1, HEY2
NOTCH4 Intracellular Domain Regulates Transcription	3	71.4×	6e-04	FLT4, HEY2, NOTCH1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	2	135.9×	0.004	JAG1, NOTCH1
VEGF binds to VEGFR leading to receptor dimerization	2	105.7×	0.004	KDR, FLT4
Complex IV assembly	3	28.6×	0.004	MT-CO1, MT-CO2, MT-CO3
Constitutive Signaling by NOTCH1 PEST Domain Mutants	3	24.6×	0.004	JAG1, HEY2, NOTCH1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	3	24.6×	0.004	JAG1, HEY2, NOTCH1
Cytoprotection by HMOX1	3	23.0×	0.005	MT-CO1, MT-CO2, MT-CO3
RUNX3 regulates NOTCH signaling	2	68.0×	0.005	JAG1, NOTCH1
YAP1- and WWTR1 (TAZ)-stimulated gene expression	2	63.4×	0.005	NKX2-5, GATA4
Constitutive Signaling by NOTCH1 HD Domain Mutants	2	63.4×	0.005	JAG1, NOTCH1
Transcriptional regulation of testis differentiation	2	59.5×	0.005	ZFPM2, GATA4
Formation of definitive endoderm	2	59.5×	0.005	GATA4, GATA6
Factors involved in megakaryocyte development and platelet production	4	11.1×	0.005	ZFPM2, GATA4, GATA6, GATA5
Physiological factors	2	56.0×	0.005	NKX2-5, GATA4
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	2	50.1×	0.006	GATA4, GATA6
TP53 Regulates Metabolic Genes	3	16.2×	0.006	MT-CO1, MT-CO2, MT-CO3
NOTCH3 Intracellular Domain Regulates Transcription	2	36.6×	0.009	HEY2, NOTCH1
Mitochondrial translation termination	3	13.7×	0.009	MT-CO1, MT-CO2, MT-CO3
Activated NOTCH1 Transmits Signal to the Nucleus	2	29.7×	0.013	JAG1, NOTCH1
Respiratory electron transport	3	11.9×	0.013	MT-CO1, MT-CO2, MT-CO3
NOTCH1 Intracellular Domain Regulates Transcription	2	19.8×	0.028	HEY2, NOTCH1
Neuropilin interactions with VEGF and VEGFR	1	119.0×	0.045	KDR
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	119.0×	0.045	JAG1
SLIT2:ROBO1 increases RHOA activity	1	119.0×	0.045	ROBO1
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	95.2×	0.046	NOTCH1
Defective LFNG causes SCDO3	1	95.2×	0.046	NOTCH1
Regulation of cortical dendrite branching	1	95.2×	0.046	ROBO1
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	95.2×	0.046	KDR
Formation of lateral plate mesoderm	1	95.2×	0.046	GATA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
aortic valve morphogenesis	7	112.0×	1e-10	NKX2-5, GATA4, JAG1, ROBO1, GATA5, HEY2, NOTCH1
cardiac septum morphogenesis	5	222.9×	4e-09	NKX2-5, JAG1, BMP7, HEY2, NOTCH1
atrioventricular node development	4	416.1×	2e-08	NKX2-5, GATA4, GATA6, NOTCH1
outflow tract septum morphogenesis	5	120.0×	7e-08	ZFPM2, NKX2-5, GATA6, ROBO1, TBX1
ventricular septum morphogenesis	5	80.0×	5e-07	ZFPM2, NKX2-5, ROBO1, HEY2, NOTCH1
pulmonary valve morphogenesis	4	138.7×	2e-06	JAG1, ROBO1, HEY2, NOTCH1
cell fate commitment	5	54.8×	2e-06	GATA4, GATA6, KDR, GATA5, HEY2
heart development	7	20.4×	3e-06	ZFPM2, NKX2-5, BMP7, POPDC1, TBX1, IRX4, NOTCH1
positive regulation of cardiac muscle cell proliferation	4	92.5×	6e-06	ZFPM2, GATA6, HEY2, NOTCH1
cardiac muscle cell proliferation	4	86.1×	7e-06	NKX2-5, GATA6, HEY2, NOTCH1
negative regulation of cardiac muscle cell apoptotic process	4	80.5×	9e-06	NKX2-5, GATA4, HEY2, NOTCH1
lymph vessel development	3	208.1×	1e-05	KDR, TBX1, FLT4
cardiac ventricle morphogenesis	3	208.1×	1e-05	GATA4, HEY2, NOTCH1
intestinal epithelial cell differentiation	3	170.2×	2e-05	GATA4, GATA6, GATA5
positive regulation of transcription by RNA polymerase II	11	6.1×	2e-05	ZFPM2, NKX2-5, GATA4, GATA6, JAG1, BMP7, TBX1, GATA5 (+3 more)
heart morphogenesis	4	55.5×	3e-05	NKX2-5, TBX1, NIPBL, EPHB4
cardiac right ventricle morphogenesis	3	156.0×	3e-05	GATA4, JAG1, HEY2
positive regulation of Notch signaling pathway	4	52.0×	3e-05	JAG1, ROBO1, GATA5, NOTCH1
atrial septum morphogenesis	3	144.0×	3e-05	NKX2-5, GATA4, HEY2
negative regulation of cardiac muscle hypertrophy	3	124.8×	5e-05	CERS1, GATA5, NOTCH1
outflow tract morphogenesis	4	45.4×	5e-05	TBX1, NIPBL, HEY2, NOTCH1
ventricular trabecula myocardium morphogenesis	3	117.0×	5e-05	NKX2-5, HEY2, NOTCH1
right ventricular cardiac muscle tissue morphogenesis	2	624.1×	6e-05	ZFPM2, NKX2-5
positive regulation of DNA-templated transcription	8	8.3×	8e-05	NKX2-5, GATA4, GATA6, BMP7, TBX1, IRX4, NOTCH1, RET
vasculogenesis	4	37.8×	8e-05	ZFPM2, NKX2-5, KDR, HEY2
pharyngeal system development	3	89.2×	1e-04	NKX2-5, BMP7, TBX1
mitochondrial electron transport, cytochrome c to oxygen	3	85.1×	1e-04	MT-CO1, MT-CO2, MT-CO3
cardiac vascular smooth muscle cell development	2	416.1×	2e-04	HEY2, NOTCH1
distal tubule development	2	416.1×	2e-04	JAG1, NOTCH1
negative regulation of transcription by RNA polymerase II	9	5.9×	2e-04	ZFPM2, NKX2-5, GATA4, GATA6, GATA5, NIPBL, HEY2, IRX4 (+1 more)

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 21

Druggability breadth: 13 of 28 evidence-associated genes (46%) 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
KDR	VANDETANIB
FLT4	FEDRATINIB
BLK	AFATINIB
EPHB4	PONATINIB
MT-CO2	CELECOXIB
RET	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDR	172	4
RET	135	4
FLT4	72	4
BLK	62	4
EPHB4	46	4
MT-CO2	6	4
NOTCH1	1	2
ZFPM2	0	0
NKX2-5	0	0
GATA4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VANDETANIB	4	BLK, EPHB4, FLT4, KDR, RET
ERLOTINIB	4	BLK, EPHB4, FLT4, KDR, RET
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	EPHB4, KDR, RET
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR, RET
FEDRATINIB	4	BLK, EPHB4, FLT4, KDR, RET
TIVOZANIB	4	EPHB4, FLT4, KDR, RET
LENVATINIB	4	FLT4, KDR, RET
AXITINIB	4	BLK, FLT4, KDR, RET
SORAFENIB	4	BLK, EPHB4, FLT4, KDR, RET
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR, RET
ESTRAMUSTINE PHOSPHATE	4	KDR
NERATINIB	4	BLK, KDR
INFIGRATINIB PHOSPHATE	4	FLT4, KDR, RET
INFIGRATINIB	4	FLT4, KDR, RET
IBRUTINIB	4	BLK, KDR, RET
REGORAFENIB	4	FLT4, KDR, RET
ENTRECTINIB	4	BLK, FLT4, KDR, RET
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	FLT4, KDR, RET
TOFACITINIB	4	KDR, RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
RET	1,586	Binding:1573, Functional:10, ADMET:3
FLT4	717	Binding:683, Functional:32, ADMET:2
BLK	483	Binding:477, ADMET:4, Functional:2
EPHB4	437	Binding:437
MT-CO2	47	Binding:41, ADMET:5, Toxicity:1
NOTCH1	23	Binding:19, ADMET:4
MT-CO1	19	Binding:12, Functional:4, ADMET:2, Toxicity:1
GATA4	5	Binding:5
CERS1	2	Binding:2
JAG1	1	Binding:1
AGPAT5	1	Binding:1
MT-CO3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDR	2.7.10.1	receptor protein-tyrosine kinase
FLT4	2.7.10.1	receptor protein-tyrosine kinase
BLK	2.7.10.2	non-specific protein-tyrosine kinase
CERS1	2.3.1.299	sphingoid base N-stearoyltransferase
AGPAT5	2.3.1.51	1-acylglycerol-3-phosphate O-acyltransferase
EPHB4	2.7.10.1	receptor protein-tyrosine kinase
MT-CO1	7.1.1.9	cytochrome-c oxidase
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KDR	2,687
FLT4	717
BLK	483
EPHB4	437
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 28; 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)
VANDETANIB	4	BLK, EPHB4, FLT4, KDR, RET
ERLOTINIB	4	BLK, EPHB4, FLT4, KDR, RET
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	EPHB4, KDR, RET
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR, RET
FEDRATINIB	4	BLK, EPHB4, FLT4, KDR, RET
TIVOZANIB	4	EPHB4, FLT4, KDR, RET
LENVATINIB	4	FLT4, KDR, RET
AXITINIB	4	BLK, FLT4, KDR, RET
SORAFENIB	4	BLK, EPHB4, FLT4, KDR, RET
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR, RET
ESTRAMUSTINE PHOSPHATE	4	KDR
NERATINIB	4	BLK, KDR
INFIGRATINIB PHOSPHATE	4	FLT4, KDR, RET
INFIGRATINIB	4	FLT4, KDR, RET
IBRUTINIB	4	BLK, KDR, RET
REGORAFENIB	4	FLT4, KDR, RET
ENTRECTINIB	4	BLK, FLT4, KDR, RET
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	FLT4, KDR, RET
TOFACITINIB	4	KDR, RET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	KDR, FLT4, BLK, EPHB4, MT-CO2, RET
B	Phased (≥1) drug, not yet approved	1	NOTCH1
C	Druggable family + PDB, no drug	3	ROBO1, FLNC, MT-CO1
D	Druggable family + AlphaFold only, no drug	2	CERS1, AGPAT5
E	Difficult family or no structure, no drug	16	ZFPM2, NKX2-5, GATA4, GATA6, JAG1, POPDC1, GATA5, BMP7, TBX1, CRELD1 (+6 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
JAG1	1	NOTCH1
HEY2	0	NOTCH1
MT-CO1	19	MT-CO2
MT-CO3	1	MT-CO2
ZFPM2	0	—
NKX2-5	0	—
GATA4	5	—
GATA6	0	—
POPDC1	0	—
GATA5	0	—
ROBO1	0	—
BMP7	0	—
TBX1	0	—
CERS1	2	—
CRELD1	0	—
ACTN2	0	—
AGPAT5	1	—
NIPBL	0	—
LIMS3	0	—
FLNC	0	—
IRX4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 74.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	63
PHASE1	3
PHASE2/PHASE3	2
PHASE2	2
PHASE4	1
PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT02590679	PHASE2/PHASE3	UNKNOWN	Multi-center Trial of Percutaneous Pulmonary Valve Implantation With Venus-p
NCT05579964	PHASE2/PHASE3	COMPLETED	The Role of Dexmedetomidine as Myocardial Protector in Pediatric Cardiac Surgery Total Correction of Tetralogy of Fallot
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905	PHASE2	UNKNOWN	Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
NCT05186415	PHASE1/PHASE2	COMPLETED	Contrast Enhanced 3D Echocardiographic Quantification of Right Ventricular Volumes in Repaired CHD
NCT04713657	PHASE1	RECRUITING	Beta-blocker Administration for Cardiomyocyte Division
NCT00573066	PHASE1	COMPLETED	Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT07194304	EARLY_PHASE1	COMPLETED	Effect of Parenteral Alpha-Tocopherol in the Definitive Surgery of Tetralogy of Fallot
NCT00243776	Not specified	RECRUITING	Molecular and Cellular Characterization of Cardiac Tissue in Postnatal Development
NCT03130777	Not specified	ACTIVE_NOT_RECRUITING	ALTERRA: SAPIEN 3 THV With the Alterra Adaptive Prestent
NCT03441971	Not specified	ACTIVE_NOT_RECRUITING	Evaluation of the GORE PV1 Device in Patients With Pulmonary Valve Dysfunction
NCT03837574	Not specified	RECRUITING	French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator
NCT03983512	Not specified	ACTIVE_NOT_RECRUITING	PULSTA Transcatheter Pulmonary Valve Pre-Approval Study
NCT04084132	Not specified	RECRUITING	Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation
NCT04106479	Not specified	RECRUITING	NIRS in Congenital Heart Defects - Correlation With Echocardiography
NCT04288596	Not specified	NOT_YET_RECRUITING	Canadian Adult Congenital Heart Disease Intervention Registry
NCT04737135	Not specified	ACTIVE_NOT_RECRUITING	Myocardial FIbrosis in Repaired Tetralogy of FAllot- FIFA Study)
NCT05122962	Not specified	RECRUITING	Pathophysiologic Mechanism for Arrhythmias and Impaired Aerobic Capacity in Tetralogy of Fallot and Other Congenital Heart Diseases
NCT05236153	Not specified	RECRUITING	Electroanatomic Interactions Between Transcatheter Pulmonary Valve Prostheses and Anatomic Isthmuses in Repaired Tetralogy of Fallot
NCT05288894	Not specified	RECRUITING	Repaired Tetralogy of Fallot Italian Registry
NCT05378386	Not specified	ACTIVE_NOT_RECRUITING	ALTERRA Post-Approval Study
NCT05809310	Not specified	RECRUITING	Effects Branch PA Stenting d-TGA, ToF and TA
NCT06282926	Not specified	ACTIVE_NOT_RECRUITING	Role of 3D Echocardiography Knowledge-based Reconstruction in ACHD
NCT06768008	Not specified	RECRUITING	An Integrated Prenatal and Postnatal Treatment Model for the Treatment of Newborns With Critical Congenital Heart Disease
NCT06771687	Not specified	RECRUITING	High Intensity Interval Training in Patients With a Right Ventricle to Pulmonary Artery Conduit
NCT06822400	Not specified	RECRUITING	Investigation of Tetralogy of Fallot in Neonates
NCT06932081	Not specified	RECRUITING	Adult Congenital Heart Disease International EValuation of the Effectiveness of SGLT2i Registry
NCT07010510	Not specified	NOT_YET_RECRUITING	Quality of Life in Operated Adult Patients With Tetralogy of Fallot and Correlation With Myocardial Strain Analysis by CMR
NCT07326228	Not specified	NOT_YET_RECRUITING	Effect of Exercises on Ventilatory Function in Adult With TOF
NCT07607821	Not specified	NOT_YET_RECRUITING	Validation of ECG-Based Ventricular Arrhythmia Localization Algorithms in Patients With Repaired Tetralogy of Fallot
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects
NCT00005190	Not specified	COMPLETED	Reproduction and Survival After Cardiac Defect Repair
NCT00112320	Not specified	COMPLETED	Comparison of Two Pulmonary Valve Replacement Methods to Treat Tetralogy of Fallot
NCT00155428	Not specified	UNKNOWN	Biomodel in Tetralogy of Fallot
NCT00266188	Not specified	COMPLETED	Follow up of Post-repair Tetralogy of Fallot
NCT00412685	Not specified	COMPLETED	Myocardial Contrast Echocardiography in Congenital Heart Disease
NCT00536432	Not specified	COMPLETED	Early Re-intervention in Infants and Small Children After Correction of Tetralogy of Fallot

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXMEDETOMIDINE	4	4
CALCIUM GLUCONATE	4	1
EPLERENONE	4	1
SODIUM CITRATE	4	1
CHEMBL4292901	0	1
alpha-TOCHOPHEROL	0	1

Cohort genes: ZFPM2, NKX2-5, GATA4, GATA6, JAG1, KDR, POPDC1, GATA5, FLT4, ROBO1, BLK, BMP7, TBX1, CERS1, CRELD1, ACTN2, AGPAT5, NIPBL, LIMS3, EPHB4, FLNC, HEY2, IRX4, MT-CO1, MT-CO2, MT-CO3, NOTCH1, RET
Drugs: Dexmedetomidine, Calcium Gluconate, Eplerenone, Sodium