Congenital heart disease

Summary

Congenital heart disease (MONDO:0005453) is a disease (an umbrella term covering 23 Mondo subtypes) caused by variants in ISL1, NKX2-6, and RBFOX2, with 83 cohort genes (41 GWAS associations across 8 studies) and 679 clinical trials. The dominant Reactome pathway is Cardiogenesis (13 cohort genes). Top therapeutic interventions include bosentan, dopamine, and phenoxybenzamine.

At a glance

• Causal genes: ISL1 (GenCC Definitive), NKX2-6 (GenCC Strong), RBFOX2 (GenCC Strong)
• Umbrella term: 23 Mondo subtypes
• Cohort genes: 83
• GWAS associations: 41
• ClinVar variants: 135
• Clinical trials: 679

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital heart disease
Mondo ID	MONDO:0005453
EFO	EFO:0005207
MeSH	D006330
DOID	DOID:1682
ICD-11	2004408087
NCIT	C95834
SNOMED CT	13213009
UMLS	C0152021
MedGen	57501
Is cancer (heuristic)	no

Also known as: abnormalities, heart · Abnormality, heart · congenital anomaly of heart · congenital heart defect · congenital heart defects · defect, congenital heart · defects, congenital heart · heart abnormalities · heart abnormality · heart defect, congenital · heart malformation · heart, malformation Of

Data availability: 135 ClinVar variants · 41 GWAS associations (8 studies) · 93 GenCC gene-disease records · 7 cell lines.

Disease family

An umbrella term covering 23 Mondo subtypes.

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

Related subtypes (33): endocardium disorder, pericardium disorder, cardiac tuberculosis, heart conduction disease, hypertensive heart disease, heart valve disorder, cardiomyopathy, coronary artery disorder, heart failure, heart aneurysm, rheumatic heart disease, cardiac rhythm disease, white forelock with malformations, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, PHACE syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, cardiac anomalies-heterotaxy syndrome, polyvalvular heart disease syndrome, Thomas syndrome, 22q11.2 deletion syndrome, myocardial rupture, heart neoplasm, aortopulmonary window, cor biloculare, inflammation of heart layer, myocardial disorder, carcinoid heart disease, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, coronary microvascular disorder, cardiac ventricle disorder, cardiogenetic disease, cardiogenic shock

Subtypes (23): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, congenital pulmonary veins anomaly, mehta lewis patton syndrome, structural congenital heart disease, multiple types - GATA4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, HAND2 related congenital heart defect, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

Genetics & variants

GWAS landscape

41 GWAS associations across 8 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2360743	7e-13	SLC44A2	T	0.02
rs870142	3e-10	STX18-AS1	A	1.46
rs55877192	1e-09	CAPN11	G	0.42
rs2316327	2e-09	RPRML - LRRC37A17P	?	1.14
rs16941382	2e-09	GOSR2	?	1.15
rs185531658	5e-09	YTHDC2 - KCNN2	?	2.16
rs56409046	3e-07	HULC - OFCC1	?	1.34
rs1941023	4e-07	MS4A12 - MS4A13	?	1.25
rs75661265	5e-07	TOX-DT - RNA5SP267	?	1.18
rs188255766	5e-07	AP3S1 - LINCADL	T	0.41
rs11895588	7e-07	LRP1B	?	1.84
rs1176869	9e-07	FBXO33 - LINC02315	?	1.35
rs1245314	9e-07	NOVA1-DT, MIR4307HG	?	1.12
rs17111230	1e-06	FBXO33 - LINC02315	?	1.3
rs66678247	1e-06	DRD3 - ATOSBP1	?	1.7
rs146189703	1e-06	ADAM29 - TSEN2P1	?	1.01
rs2844660	1e-06	LINC02570 - RN7SKP186	?	1.37
rs7212330	2e-06	CLEC10A - ASGR2	?	1.42
rs1217752	2e-06	CARTPT - MAP1B	?	1.08
rs28549925	2e-06	AHR	?	1.16
rs78642028	2e-06	SOX5P1 - DCAF4L2	?	1.66
rs5913271	2e-06	TENT5D - HNRNPH3P1	A	0.27
rs11816084	3e-06	KRT8P37 - CHCHD3P1	?	1.36
rs35611996	3e-06	SCHIP1, IQCJ-SCHIP1	?	1.01
rs4688406	4e-06	SYNPR-AS1, SYNPR	?	1.29
rs56171387	4e-06	TMEM104	?	1.06
rs9341603	4e-06	LINC02540 - HTR1B	T	1.42
rs1450832	5e-06	FOXP2	?	1.1
rs9586881	5e-06	LINC00373	?	1.07
rs12716944	6e-06	MPHOSPH6-DT - CDH13	?	1.29

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011989	Lahm H	2020	4,034	8,486	Congenital heart disease risk loci identified by genome-wide association study in European patients.
GCST90570531	Broberg M	2024	3,506	392,436	Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.
GCST002035	Cordell HJ	2013	1,479	5,159	Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.
GCST90131426	Rashkin SR	2022	0	0	A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.
GCST90131427	Rashkin SR	2022	0	0	A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.
GCST90131428	Rashkin SR	2022	0	0	A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.
GCST004718	Agopian AJ	2017	0	2,976	Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.
GCST004721	Agopian AJ	2017	0	0	Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	37
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	31
intergenic_variant	9
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2360743	19	10625838	C>T		intron_variant	SLC44A2	7e-13	Tier 4: intronic/intergenic
rs870142	4	4646320	C>G,T	0.228	intron_variant	STX18-AS1	3e-10	Tier 4: intronic/intergenic
rs55877192	6	44161476	A>G	0.05	intron_variant	CAPN11	1e-09	Tier 4: intronic/intergenic
rs2316327	17	47001132	G>A,C	0.05	intron_variant	RPRML - LRRC37A17P	2e-09	Tier 4: intronic/intergenic
rs16941382	17	46966142	T>C	0.05	intron_variant	GOSR2	2e-09	Tier 4: intronic/intergenic
rs185531658	5	113800824	T>C		intron_variant	YTHDC2 - KCNN2	5e-09	Tier 4: intronic/intergenic
rs56409046	6	9320073	C>T	0.05	intergenic_variant	HULC - OFCC1	3e-07	Tier 4: intronic/intergenic
rs1941023	11	60508428	G>A	0.05	intergenic_variant	MS4A12 - MS4A13	4e-07	Tier 4: intronic/intergenic
rs75661265	8	59275232	C>T	0.05	intron_variant	TOX-DT - RNA5SP267	5e-07	Tier 4: intronic/intergenic
rs188255766	5	115946361	C>T		intergenic_variant	AP3S1 - LINCADL	5e-07	Tier 4: intronic/intergenic
rs11895588	2	141204588	G>T	0.05	intron_variant	LRP1B	7e-07	Tier 4: intronic/intergenic
rs1176869	14	40807221	C>G	0.05	intron_variant	FBXO33 - LINC02315	9e-07	Tier 4: intronic/intergenic
rs1245314	14	27023434	A>C,G,T	0.05	intron_variant	NOVA1-DT, MIR4307HG	9e-07	Tier 4: intronic/intergenic
rs17111230	14	40922047	G>A,C,T	0.05	intergenic_variant	FBXO33 - LINC02315	1e-06	Tier 4: intronic/intergenic
rs66678247	3	114227412	T>C	0.05	intron_variant	DRD3 - ATOSBP1	1e-06	Tier 4: intronic/intergenic
rs146189703	4	175023930	T>A,C	0.05	intron_variant	ADAM29 - TSEN2P1	1e-06	Tier 4: intronic/intergenic
rs2844660	6	30855983	T>C	0.05	intergenic_variant	LINC02570 - RN7SKP186	1e-06	Tier 4: intronic/intergenic
rs7212330	17	7100096	A>G	0.05	intergenic_variant	CLEC10A - ASGR2	2e-06	Tier 4: intronic/intergenic
rs1217752	5	71956619	A>T	0.05	intron_variant	CARTPT - MAP1B	2e-06	Tier 4: intronic/intergenic
rs28549925	7	16931967	A>G	0.05	intron_variant	AHR	2e-06	Tier 4: intronic/intergenic
rs78642028	8	87811731	A>G	0.05	non_coding_transcript_exon_variant	SOX5P1 - DCAF4L2	2e-06	Tier 4: intronic/intergenic
rs5913271	X	80475711	T>A,C	0.05	intron_variant	TENT5D - HNRNPH3P1	2e-06	Tier 4: intronic/intergenic
rs11816084	10	8519464	C>A,T	0.05	intergenic_variant	KRT8P37 - CHCHD3P1	3e-06	Tier 4: intronic/intergenic
rs35611996	3	159298001	C>T	0.05	intron_variant	SCHIP1, IQCJ-SCHIP1	3e-06	Tier 4: intronic/intergenic
rs4688406	3	63495718	T>G	0.05	intron_variant	SYNPR-AS1, SYNPR	4e-06	Tier 4: intronic/intergenic
rs56171387	17	74829334	G>A	0.05	intron_variant	TMEM104	4e-06	Tier 4: intronic/intergenic
rs9341603	6	76825236	C>T	0.05	intron_variant	LINC02540 - HTR1B	4e-06	Tier 4: intronic/intergenic
rs1450832	7	114223329	G>A,T	0.05	intron_variant	FOXP2	5e-06	Tier 4: intronic/intergenic
rs9586881	13	88185775	A>G	0.05	intron_variant	LINC00373	5e-06	Tier 4: intronic/intergenic
rs12716944	16	82445019	C>A,G,T	0.05	intergenic_variant	MPHOSPH6-DT - CDH13	6e-06	Tier 4: intronic/intergenic

ClinVar germline variants

135 retrieved; paginated sample, class counts are floors:

58 uncertain significance, 23 conflicting classifications of pathogenicity, 17 pathogenic, 11 benign/likely benign, 9 likely pathogenic, 8 pathogenic/likely pathogenic, 5 benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
374794	NM_005157.6(ABL1):c.1009G>A (p.Ala337Thr)	ABL1	Pathogenic	criteria provided, multiple submitters, no conflicts
374795	NM_005157.6(ABL1):c.677A>G (p.Tyr226Cys)	ABL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4846746	GRCh38/hg38 22q11.21(chr22:18932238-20324016)x3	ARVCF	Pathogenic	criteria provided, single submitter
1307836	NM_015557.3(CHD5):c.4852C>T (p.Arg1618Ter)	CHD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1358881	NM_001372.4(DNAH9):c.4719T>G (p.Tyr1573Ter)	DNAH9	Pathogenic	criteria provided, single submitter
1911635	NM_001372.4(DNAH9):c.4030C>T (p.Arg1344Ter)	DNAH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219226	NM_001308093.3(GATA4):c.23C>A (p.Ala8Asp)	GATA4	Pathogenic	no assertion criteria provided
219228	NM_001308093.3(GATA4):c.383A>T (p.Glu128Val)	GATA4	Pathogenic	no assertion criteria provided
219229	NM_001308093.3(GATA4):c.397A>T (p.Ser133Cys)	GATA4	Pathogenic	no assertion criteria provided
219230	NM_001308093.3(GATA4):c.685T>A (p.Trp229Arg)	GATA4	Pathogenic	no assertion criteria provided
219231	NM_001308093.3(GATA4):c.27C>A (p.Ala9=)	GATA4	Pathogenic	no assertion criteria provided
219232	NM_001308093.3(GATA4):c.1266C>T (p.Ser422=)	GATA4	Pathogenic	no assertion criteria provided
219233	NM_001308093.3(GATA4):c.1000+2T>G	GATA4	Pathogenic	no assertion criteria provided
433018	NM_001308093.3(GATA4):c.913-55T>C	GATA4	Pathogenic	no assertion criteria provided
4075076	NM_147191.1(MMP21):c.1260C>G (p.Asp420Glu)	MMP21	Pathogenic	criteria provided, single submitter
1202626	NM_000432.4(MYL2):c.473T>C (p.Ile158Thr)	MYL2	Pathogenic	no assertion criteria provided
219165	NM_004387.4(NKX2-5):c.335-1G>T	NKX2-5	Pathogenic	no assertion criteria provided
219168	NM_004387.4(NKX2-5):c.391G>A (p.Glu131Lys)	NKX2-5	Pathogenic	no assertion criteria provided
219170	NM_004387.4(NKX2-5):c.182C>G (p.Ala61Gly)	NKX2-5	Pathogenic	no assertion criteria provided
219378	NM_017617.5(NOTCH1):c.1649dup (p.Tyr550Ter)	NOTCH1	Pathogenic	criteria provided, multiple submitters, no conflicts
41442	NM_002834.5(PTPN11):c.178G>T (p.Gly60Cys)	PTPN11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2753661	NM_004260.4(RECQL4):c.236_237insCA (p.Pro80fs)	RECQL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56407	NM_004260.4(RECQL4):c.3072del (p.Val1026fs)	RECQL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
181522	NM_006912.6(RIT1):c.246T>G (p.Phe82Leu)	RIT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1077090	NM_002941.4(ROBO1):c.2758C>T (p.Arg920Ter)	ROBO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929503	NM_005632.2:c.2904+1_2905-45del	CAPN15	Likely pathogenic	criteria provided, single submitter
4075256	NM_001791.4(CDC42):c.67T>C (p.Tyr23His)	CDC42	Likely pathogenic	criteria provided, single submitter
4074816	NM_006766.5(KAT6A):c.5202del (p.Ile1735fs)	KAT6A	Likely pathogenic	criteria provided, single submitter
4820339	NM_003482.4(KMT2D):c.7207dup (p.Leu2403fs)	KMT2D	Likely pathogenic	criteria provided, single submitter
3900742	NM_004991.4(MECOM):c.2831C>T (p.Thr944Ile)	MECOM	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 378 · Orphanet: 113 · 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
ISL1	Definitive	Autosomal dominant	congenital heart disease
GJA1	Strong	Autosomal dominant	autosomal dominant palmoplantar keratoderma and congenital alopecia	25
NKX2-6	Strong	Autosomal recessive	congenital heart disease	4
PRKD1	Strong	Autosomal dominant	congenital heart defects and ectodermal dysplasia	14
RBFOX2	Strong	Autosomal dominant	congenital heart defects, multiple types	3
SCN5A	Strong	Autosomal dominant	progressive familial heart block, type 1A	23
SMAD2	Strong	Autosomal dominant	congenital heart defects, multiple types, 8, with or without heterotaxy	11
CITED2	Moderate	Autosomal dominant	congenital heart defects, multiple types	4
ETS1	Moderate	Autosomal dominant	congenital heart disease	4
FGF8	Moderate	Autosomal dominant	congenital heart disease	9
FOXH1	Moderate	Autosomal dominant	congenital heart disease	2
HAND1	Moderate	Autosomal dominant	congenital heart disease	2
HAND2	Moderate	Autosomal dominant	HAND2 related congenital heart defect	4
KLF13	Moderate	Autosomal dominant	congenital heart disease
MESP1	Moderate	Autosomal dominant	congenital heart disease	2
ROCK2	Moderate	Autosomal dominant	congenital heart disease	2
TBX20	Moderate	Autosomal dominant	congenital heart disease	5
MYH7	Supportive	Autosomal dominant	congenital myopathy 7A, myosin storage, autosomal dominant	20
ACVR1	Limited	Autosomal dominant	congenital heart disease	7
ADAM17	Limited	Autosomal dominant	congenital heart disease	6
ADAMTS19	Limited	Autosomal recessive	congenital heart disease	4
ANKRD1	Limited	Autosomal dominant	congenital heart disease	5
BCL9	Limited	Autosomal dominant	congenital heart disease
BMP10	Limited	Autosomal dominant	congenital heart disease	4
CASZ1	Limited	Autosomal dominant	congenital heart disease
CHRD	Limited	Autosomal recessive	congenital heart disease
CRELD1	Limited	Autosomal dominant	congenital heart disease	5
CRIPTO	Limited	Autosomal dominant	congenital heart disease	2
EFNB2	Limited	Autosomal dominant	congenital heart disease
ETV2	Limited	Autosomal recessive	congenital heart disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome
SCN5A	Orphanet:101016	Romano-Ward syndrome
SCN5A	Orphanet:130	Brugada syndrome
SCN5A	Orphanet:1344	Isolated atrial standstill
SCN5A	Orphanet:154	Familial isolated dilated cardiomyopathy
SCN5A	Orphanet:166282	Hereditary sick sinus syndrome
SCN5A	Orphanet:228140	Idiopathic ventricular fibrillation
SCN5A	Orphanet:334	Hereditary atrial fibrillation
SCN5A	Orphanet:871	Hereditary progressive cardiac conduction defect
DCHS1	Orphanet:314679	Cerebrofacioarticular syndrome
DCHS1	Orphanet:741	Familial mitral valve prolapse
CRELD1	Orphanet:576235	Partial atrioventricular septal defect without ventricular hypoplasia
CRELD1	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
CRELD1	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
ACVR1	Orphanet:337	Fibrodysplasia ossificans progressiva
CTNNA3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
CTNNA3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
CTNNA3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DTNA	Orphanet:54260	Left ventricular noncompaction
FOXP1	Orphanet:391372	FOXP1 Syndrome
FOXP1	Orphanet:52417	MALT lymphoma
FOXP1	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
LRP2	Orphanet:2143	Donnai-Barrow syndrome
RECQL4	Orphanet:1225	Baller-Gerold syndrome
RECQL4	Orphanet:221016	Rothmund-Thomson syndrome type 2
RECQL4	Orphanet:3021	RAPADILINO syndrome
TBX20	Orphanet:54260	Left ventricular noncompaction
TBX20	Orphanet:99103	Atrial septal defect, ostium secundum type
CRIPTO	Orphanet:220386	Semilobar holoprosencephaly
CRIPTO	Orphanet:280195	Septopreoptic holoprosencephaly
CRIPTO	Orphanet:280200	Microform holoprosencephaly
CRIPTO	Orphanet:93924	Lobar holoprosencephaly
CRIPTO	Orphanet:93925	Alobar holoprosencephaly
CRIPTO	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
TLL1	Orphanet:99103	Atrial septal defect, ostium secundum type
TLL1	Orphanet:99106	Atrial septal defect, ostium primum type
VCL	Orphanet:154	Familial isolated dilated cardiomyopathy
ANKRD1	Orphanet:154	Familial isolated dilated cardiomyopathy
ADAM17	Orphanet:294023	Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome
CITED2	Orphanet:101063	Situs inversus totalis
CITED2	Orphanet:3303	Tetralogy of Fallot
CITED2	Orphanet:99103	Atrial septal defect, ostium secundum type
CITED2	Orphanet:99105	Atrial septal defect, sinus venosus type
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

Cohort genes → proteins

83 cohort genes, 83 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	83

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	gencc,clinvar
SCN5A	HGNC:10593	ENSG00000183873	Q14524	Sodium channel protein type 5 subunit alpha	gencc,clinvar
WDR5	HGNC:12757	ENSG00000196363	P61964	WD repeat-containing protein 5	gencc,clinvar
KLF13	HGNC:13672	ENSG00000169926	Q9Y2Y9	Krueppel-like factor 13	gencc,clinvar
DCHS1	HGNC:13681	ENSG00000166341	Q96JQ0	Protocadherin-16	gencc,clinvar
CRELD1	HGNC:14630	ENSG00000163703	Q96HD1	Protein disulfide isomerase CRELD1	gencc,clinvar
ACVR1	HGNC:171	ENSG00000115170	Q04771	Activin receptor type-1	gencc,clinvar
CTNNA3	HGNC:2511	ENSG00000183230	Q9UI47	Catenin alpha-3	gencc,clinvar
DTNA	HGNC:3057	ENSG00000134769	Q9Y4J8	Dystrobrevin alpha	gencc,clinvar
FOXP1	HGNC:3823	ENSG00000114861	Q9H334	Forkhead box protein P1	gencc,clinvar
LRP2	HGNC:6694	ENSG00000081479	P98164	Low-density lipoprotein receptor-related protein 2	gencc,clinvar
RBFOX2	HGNC:9906	ENSG00000100320	O43251	RNA binding protein fox-1 homolog 2	gencc,clinvar
RECQL4	HGNC:9949	ENSG00000160957	O94761	ATP-dependent DNA helicase Q4	gencc,clinvar
BCL9	HGNC:1008	ENSG00000116128	O00512	B-cell CLL/lymphoma 9 protein	gencc
ROCK2	HGNC:10252	ENSG00000134318	O75116	Rho-associated protein kinase 2	gencc
RXRA	HGNC:10477	ENSG00000186350	P19793	Retinoic acid receptor RXR-alpha	gencc
SRF	HGNC:11291	ENSG00000112658	P11831	Serum response factor	gencc
TBX20	HGNC:11598	ENSG00000164532	Q9UMR3	T-box transcription factor TBX20	gencc
TCF21	HGNC:11632	ENSG00000118526	O43680	Transcription factor 21	gencc
CRIPTO	HGNC:11701	ENSG00000241186	P13385	Protein Cripto	gencc
TLL1	HGNC:11843	ENSG00000038295	O43897	Tolloid-like protein 1	gencc
VCL	HGNC:12665	ENSG00000035403	P18206	Vinculin	gencc
VEGFA	HGNC:12680	ENSG00000112715	P15692	Vascular endothelial growth factor A, long form	gencc
WNT11	HGNC:12776	ENSG00000085741	O96014	Protein Wnt-11	gencc
ANKRD1	HGNC:15819	ENSG00000148677	Q15327	Ankyrin repeat domain-containing protein 1	gencc
MAML2	HGNC:16259	ENSG00000184384	Q8IZL2	Mastermind-like protein 2	gencc
RNF40	HGNC:16867	ENSG00000103549	O75150	E3 ubiquitin-protein ligase BRE1B	gencc
ADAMTS19	HGNC:17111	ENSG00000145808	Q8TE59	A disintegrin and metalloproteinase with thrombospondin motifs 19	gencc
CHRD	HGNC:1949	ENSG00000090539	Q9H2X0	Chordin	gencc
ADAM17	HGNC:195	ENSG00000151694	P78536	Disintegrin and metalloproteinase domain-containing protein 17	gencc
ZFPM1	HGNC:19762	ENSG00000179588	Q8IX07	Zinc finger protein ZFPM1	gencc
CITED2	HGNC:1987	ENSG00000164442	Q99967	Cbp/p300-interacting transactivator 2	gencc
USP44	HGNC:20064	ENSG00000136014	Q9H0E7	Ubiquitin carboxyl-terminal hydrolase 44	gencc
USP34	HGNC:20066	ENSG00000115464	Q70CQ2	Ubiquitin carboxyl-terminal hydrolase 34	gencc
BMP10	HGNC:20869	ENSG00000163217	O95393	Bone morphogenetic protein 10	gencc
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	gencc
SORBS2	HGNC:24098	ENSG00000154556	O94875	Sorbin and SH3 domain-containing protein 2	gencc
CSRP1	HGNC:2469	ENSG00000159176	P21291	Cysteine and glycine-rich protein 1	gencc
CASZ1	HGNC:26002	ENSG00000130940	Q86V15	Zinc finger protein castor homolog 1	gencc
DAND5	HGNC:26780	ENSG00000179284	Q8N907	DAN domain family member 5	gencc
WDR47	HGNC:29141	ENSG00000085433	O94967	WD repeat-containing protein 47	gencc
MESP1	HGNC:29658	ENSG00000166823	Q9BRJ9	Mesoderm posterior protein 1	gencc
LEFTY2	HGNC:3122	ENSG00000143768	O00292	Left-right determination factor 2	gencc
EFNB2	HGNC:3227	ENSG00000125266	P52799	Ephrin-B2	gencc
NKX2-6	HGNC:32940	ENSG00000180053	A6NCS4	Homeobox protein Nkx-2.6	gencc
ETS1	HGNC:3488	ENSG00000134954	P14921	Protein C-ets-1	gencc
ETV2	HGNC:3491	ENSG00000105672	O00321	ETS translocation variant 2	gencc
FBLN2	HGNC:3601	ENSG00000163520	P98095	Fibulin-2	gencc
FGF8	HGNC:3686	ENSG00000107831	P55075	Fibroblast growth factor 8	gencc
FMO5	HGNC:3773	ENSG00000131781	P49326	Flavin-containing monooxygenase 5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
SCN5A	Sodium channel protein type 5 subunit alpha	Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
WDR5	WD repeat-containing protein 5	Contributes to histone modification.
KLF13	Krueppel-like factor 13	Transcription factor that activates expression from GC-rich minimal promoter regions, including genes in the cells of the erythroid lineage.
DCHS1	Protocadherin-16	Calcium-dependent cell-adhesion protein.
CRELD1	Protein disulfide isomerase CRELD1	Protein disulfide isomerase.
ACVR1	Activin receptor type-1	Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation.
CTNNA3	Catenin alpha-3	May be involved in formation of stretch-resistant cell-cell adhesion complexes.
DTNA	Dystrobrevin alpha	May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.
FOXP1	Forkhead box protein P1	Transcriptional repressor.
LRP2	Low-density lipoprotein receptor-related protein 2	Multiligand endocytic receptor.
RBFOX2	RNA binding protein fox-1 homolog 2	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
RECQL4	ATP-dependent DNA helicase Q4	An ATP-dependent DNA helicase which unwinds dsDNA with a 3’-overhang in a 3’-5’ direction.
BCL9	B-cell CLL/lymphoma 9 protein	Involved in signal transduction through the Wnt pathway.
ROCK2	Rho-associated protein kinase 2	Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
RXRA	Retinoic acid receptor RXR-alpha	Receptor for retinoic acid that acts as a transcription factor.
SRF	Serum response factor	SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5’ of the site of transcription initiation of some genes (such as FOS).
TBX20	T-box transcription factor TBX20	Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart.
TCF21	Transcription factor 21	Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
CRIPTO	Protein Cripto	GPI-anchored cell membrane protein involved in Nodal signaling.
TLL1	Tolloid-like protein 1	Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase.
VCL	Vinculin	Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion.
VEGFA	Vascular endothelial growth factor A, long form	Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A.
WNT11	Protein Wnt-11	Ligand for members of the frizzled family of seven transmembrane receptors.
ANKRD1	Ankyrin repeat domain-containing protein 1	May play an important role in endothelial cell activation.
MAML2	Mastermind-like protein 2	Acts as a transcriptional coactivator for NOTCH proteins.
RNF40	E3 ubiquitin-protein ligase BRE1B	Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of ‘Lys-120’ of histone H2B (H2BK120ub1).
CHRD	Chordin	Dorsalizing factor.
ADAM17	Disintegrin and metalloproteinase domain-containing protein 17	Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity.
ZFPM1	Zinc finger protein ZFPM1	Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation.
CITED2	Cbp/p300-interacting transactivator 2	Transcriptional coactivator of the p300/CBP-mediated transcription complex.
USP44	Ubiquitin carboxyl-terminal hydrolase 44	Deubiquitinase that plays a key regulatory role in the spindle assembly checkpoint or mitotic checkpoint by preventing premature anaphase onset.
USP34	Ubiquitin carboxyl-terminal hydrolase 34	Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway.
BMP10	Bone morphogenetic protein 10	Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors suc…
COL1A2	Collagen alpha-2(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
SORBS2	Sorbin and SH3 domain-containing protein 2	Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton.
CSRP1	Cysteine and glycine-rich protein 1	Could play a role in neuronal development.
CASZ1	Zinc finger protein castor homolog 1	Transcriptional activator.
DAND5	DAN domain family member 5	Antagonist of the extracellular signaling protein NODAL, which is required for correct left-right patterning during embryonic development.
MESP1	Mesoderm posterior protein 1	Transcription factor.
LEFTY2	Left-right determination factor 2	Required for left-right (L-R) asymmetry determination of organ systems in mammals.
EFNB2	Ephrin-B2	Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.
NKX2-6	Homeobox protein Nkx-2.6	Acts as a transcriptional activator.
ETS1	Protein C-ets-1	Transcription factor.
ETV2	ETS translocation variant 2	Binds to DNA sequences containing the consensus pentanucleotide 5’-CGGA[AT]-3’.
FBLN2	Fibulin-2	Its binding to fibronectin and some other ligands is calcium dependent.
FGF8	Fibroblast growth factor 8	Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration.
FMO5	Flavin-containing monooxygenase 5	Acts as a Baeyer-Villiger monooxygenase on a broad range of substrates.
FOXH1	Forkhead box protein H1	Transcriptional activator.
FOXL1	Forkhead box protein L1	Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium.

Protein-family classification

Druggable: 24 · Difficult: 32 · Unknown: 27 · Druggable fraction: 0.29

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
Transcription factor	27	2.7×	8e-06
Protease	6	2.6×	0.130
Kinase	6	2.0×	0.264
Nuclear receptor	1	4.7×	0.388
Ion channel	2	2.7×	0.388
Complement	1	3.2×	0.445
Scaffold/PPI	5	1.0×	0.755
Enzyme (other)	6	0.9×	0.869
Antibody/Immunoglobulin	2	0.7×	0.869
Other/Unknown	27	0.6×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SCN5A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a5su
WDR5	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
KLF13	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
DCHS1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CRELD1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ACVR1	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
CTNNA3	Other/Unknown	no		Alpha_catenin, Vinculin/catenin, Alpha-catenin/vinculin-like_sf
DTNA	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
FOXP1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
LRP2	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
RBFOX2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
RECQL4	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, DNA_helicase_ATP-dep_RecQ, DEAD/DEAH_box_helicase_dom
BCL9	Transcription factor	no		Znf_RING/FYVE/PHD, Bcl-9/Bcl-9l, BCL9_beta-catenin-bd_dom
ROCK2	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PH_domain
RXRA	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
SRF	Transcription factor	no		TF_MADSbox, SRF-like_MADS-box, TF_MADSbox_sf
TBX20	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TCF21	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
CRIPTO	Other/Unknown	no		EGF, Cripto, Cryptic/Cripto_CFC-dom
TLL1	Protease	yes		EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
VCL	Other/Unknown	no		Vinculin_CS, Vinculin/catenin, Vinculin
VEGFA	Other/Unknown	no		PDGF/VEGF_dom, PD_growth_factor_CS, VEGF_C
WNT11	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
ANKRD1	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
MAML2	Other/Unknown	no		Mastermind-like_N, MAML1-3, MAML_N_sf
RNF40	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, E3_ubiquit_lig_Bre1
ADAMTS19	Protease	yes		TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich
CHRD	Other/Unknown	no		VWF_dom, CHRD, Chordin
ADAM17	Protease	yes	3.4.24.86	Peptidase_M12B, Disintegrin_dom, MetalloPept_cat_dom_sf
ZFPM1	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
CITED2	Other/Unknown	no		CITED
USP44	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD
USP34	Protease	yes		Peptidase_C19_UCH, ARM-type_fold, USP_CS
BMP10	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily
SORBS2	Transcription factor	no		SH3_domain, SoHo_dom, Znf_C2H2_type
CSRP1	Transcription factor	no		Znf_LIM
CASZ1	Transcription factor	no		Znf_C2H2_type, CASZ1
DAND5	Other/Unknown	no		DAN_dom, Cerberus, Cystine-knot_cytokine
WDR47	Scaffold/PPI	no		WD40_rpt, LisH, CTLH_C
MESP1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, Mesogenin/MesP
LEFTY2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, LRDF
EFNB2	Other/Unknown	no		Ephrin_RBD, Cupredoxin, Ephrin_CS
NKX2-6	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
ETS1	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
ETV2	Other/Unknown	no		Ets_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
FBLN2	Complement	yes		Anaphylatoxin/fibulin, EGF-type_Asp/Asn_hydroxyl_site, EGF
FGF8	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FMO5	Enzyme (other)	yes	1.14.13.8	Flavin_mOase, Flavin_mOase_5, Flavin_mOase-like

Expression context

Cohort genes with no expression data: 0.

76 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)	1
broad (>20)	82
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	7
apex of heart	7
popliteal artery	7
ganglionic eminence	6
right atrium auricular region	6
primordial germ cell in gonad	6
secondary oocyte	6
tibial artery	6
cortical plate	5
cardiac atrium	5
oocyte	5
tibia	4
pancreatic ductal cell	4
calcaneal tendon	4
stromal cell of endometrium	4
male germ line stem cell (sensu Vertebrata) in testis	4
left testis	3
cerebellar hemisphere	3
right hemisphere of cerebellum	3
cartilage tissue	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia
SCN5A	161	broad	yes	apex of heart, heart left ventricle, cardiac ventricle
WDR5	245	ubiquitous	marker	upper arm skin, left testis, right testis
KLF13	169	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
DCHS1	259	broad	marker	tendon of biceps brachii, ganglionic eminence, cortical plate
CRELD1	134	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ACVR1	293	ubiquitous	marker	cartilage tissue, synovial joint, saphenous vein
CTNNA3	211	broad	marker	corpus callosum, heart right ventricle, medial globus pallidus
DTNA	266	ubiquitous	marker	medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord
FOXP1	256	ubiquitous	marker	pancreatic ductal cell, oviduct epithelium, cardia of stomach
LRP2	169	broad	marker	adult organism, adult mammalian kidney, corpus callosum
RBFOX2	144	ubiquitous	marker	cortical plate, embryo, ganglionic eminence
RECQL4	212	ubiquitous	yes	lower esophagus mucosa, ventricular zone, mucosa of transverse colon
BCL9	198	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
ROCK2	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, middle temporal gyrus
RXRA	294	ubiquitous	marker	skin of hip, gingival epithelium, pancreatic ductal cell
SRF	290	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, muscle layer of sigmoid colon
TBX20	52	broad	marker	right atrium auricular region, cardiac atrium, heart
TCF21	175	broad	marker	primordial germ cell in gonad, right lung, upper lobe of left lung
CRIPTO	124	tissue_specific	marker	adrenal tissue, primordial germ cell in gonad, metanephros cortex
TLL1	162	broad	marker	secondary oocyte, buccal mucosa cell, primordial germ cell in gonad
VCL	300	ubiquitous	marker	saphenous vein, blood vessel layer, urethra
VEGFA	297	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
WNT11	178	broad	marker	omental fat pad, peritoneum, adipose tissue of abdominal region
ANKRD1	155	ubiquitous	marker	apex of heart, right atrium auricular region, cardiac atrium
MAML2	238	ubiquitous	marker	mucosa of paranasal sinus, cartilage tissue, mammary duct
RNF40	235	ubiquitous	marker	ventricular zone, cortical plate, left testis
ADAMTS19	137	broad	marker	adrenal tissue, buccal mucosa cell, body of uterus
CHRD	185	broad	marker	right lobe of liver, right hemisphere of cerebellum, cerebellar hemisphere
ADAM17	294	ubiquitous	marker	oocyte, adrenal tissue, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 53.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HDAC1	10,279
WDR5	6,596
RECQL4	6,330
SMAD2	5,751
PDGFRA	5,186
KIF20A	5,046
GJA1	4,942
FGF8	4,536
VCL	4,495
NTRK3	4,147

Intra-cohort edges

A	B	Sources
ACVR1	BMP10	string_interaction
BCL9	FMO5	string_interaction
BMP10	MYH7	string_interaction
CASZ1	HDAC1	intact
CASZ1	TBX20	string_interaction
CHRD	DAND5	string_interaction
CHRD	TLL1	string_interaction
CITED2	LEFTY2	string_interaction
CRELD1	GJA1	string_interaction
CRIPTO	FOXH1	string_interaction
CRIPTO	LEFTY2	string_interaction
CRIPTO	SMAD2	string_interaction
CTNNA3	VCL	string_interaction
DAND5	FOXH1	string_interaction
DAND5	LEFTY2	string_interaction
EFNB2	HEY2	string_interaction
EFNB2	MESP1	string_interaction
FMO5	GJA5	string_interaction
FMO5	PRKAB2	string_interaction
FOXH1	HAND2	string_interaction
FOXH1	HEY1	intact
FOXH1	LEFTY2	string_interaction
FOXH1	SMAD1	string_interaction
FOXH1	SMAD2	biogrid_interaction, intact, string_interaction
GJA1	GJA5	string_interaction
GJA1	LEFTY2	string_interaction
GJA1	SCN5A	string_interaction
GJA5	PRKAB2	string_interaction
GJA5	SCN5A	string_interaction
HAND1	HEY2	biogrid_interaction
HAND2	IRX4	string_interaction
HAND2	MESP1	string_interaction
HAND2	NKX2-6	string_interaction
HAND2	TBX20	string_interaction
HDAC1	KDM5A	intact, string_interaction
HDAC1	MYH7	intact
HDAC1	ZFPM1	string_interaction
HEY1	HEY2	biogrid_interaction, intact
HEY2	IRX4	string_interaction
IRX4	TBX20	string_interaction
ISL1	NFATC1	biogrid_interaction
ISL1	RNF40	biogrid_interaction
KCNJ2	ROCK2	biogrid_interaction
MYBPC3	MYH7	intact, string_interaction
MYH11	SRF	string_interaction
NKX2-6	TBX20	string_interaction
NRP1	VEGFA	intact
SMAD1	SMAD2	string_interaction
SMAD1	SMAD7	biogrid_interaction
SORBS2	VCL	string_interaction

Structural data

PDB: 50 · AlphaFold-only: 33 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR5	P61964	199
RXRA	P19793	110
ACVR1	Q04771	85
VEGFA	P15692	56
KDM5A	P29375	46
MYH7	P12883	43
VCL	P18206	37
ADAM17	P78536	33
NRP1	O14786	25
ROCK2	O75116	21
ETS1	P14921	21
GJA1	P17302	19
MYBPC3	Q14896	17
PRKAB2	O43741	17
SCN5A	Q14524	16
PDGFRA	P16234	15
ROBO1	Q9Y6N7	12
HDAC1	Q13547	12
EFNB2	P52799	10
SMAD1	Q15797	10
SMAD2	Q15796	10
BCL9	O00512	8
BMP10	O95393	8
SMAD7	O15105	7
COL1A2	P08123	5
NTRK3	Q16288	5
LRP2	P98164	4
RNF40	O75150	4
CITED2	Q99967	4
SRF	P11831	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FMO5	P49326	95.03
HAS2	Q92819	90.63
WNT11	O96014	90.35
ANKRD1	Q15327	82.64
PCSK6	P29122	81.84
CRELD1	Q96HD1	81.68
CTNNA3	Q9UI47	81.65
LEFTY2	O00292	79.01
CHRD	Q9H2X0	73.95
USP44	Q9H0E7	72.63
ISL1	P61371	72.57
CSRP1	P21291	72.49
GJA5	P36382	70.35
DAND5	Q8N907	70.04
PRKD1	Q15139	68.99
ADAMTS19	Q8TE59	68.76
TBX20	Q9UMR3	67.87
FBLN2	P98095	67.85
WDR47	O94967	67.49
CRIPTO	P13385	67.47
HAND2	P61296	67.30
TCF21	O43680	66.67
HAND1	O96004	65.87
HEY2	Q9UBP5	65.56
NKX2-6	A6NCS4	64.31
FOXL1	Q12952	64.30
MESP1	Q9BRJ9	62.31
OSR1	Q8TAX0	60.59
KLF13	Q9Y2Y9	58.91
ETV2	O00321	57.35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 796. Enrichment computed across 161 evidence-associated genes (121 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 121 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cardiogenesis	13	45.4×	2e-16	WDR5, SRF, TBX20, NKX2-5, CTNNB1, MESP1, GATA4, HAND1 (+5 more)
NOTCH4 Intracellular Domain Regulates Transcription	6	28.3×	1e-05	MAML2, HEY1, HEY2, NOTCH1, NOTCH2, NOTCH4
Developmental Biology	27	3.2×	1e-05	ROBO1, SCN5A, ROCK2, RXRA, BMP4, SOS2, SRF, TBX20 (+19 more)
Signaling by NODAL	6	24.6×	2e-05	CRIPTO, DAND5, LEFTY2, FOXH1, SMAD2, PCSK6
Signaling by TGFB family members	9	8.6×	2e-04	RXRA, CBL, BMP10, LTBP1, SMAD1, SMAD2, SMAD5, SMAD6 (+1 more)
Constitutive Signaling by NOTCH1 PEST Domain Mutants	7	11.4×	3e-04	MAML2, ADAM17, HDAC1, HEY1, HEY2, JAG1, NOTCH1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	7	11.4×	3e-04	MAML2, ADAM17, HDAC1, HEY1, HEY2, JAG1, NOTCH1
Notch-HLH transcription pathway	5	16.9×	1e-03	MAML2, HDAC1, NOTCH1, NOTCH2, NOTCH4
Defective LFNG causes SCDO3	3	56.6×	0.001	NOTCH1, NOTCH2, NOTCH4
Signal Transduction	28	2.4×	0.001	BCL9, ROCK2, RXRA, SMC1A, SOS2, SRF, CBL, SALL4 (+20 more)
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	8.5×	0.001	WDR5, KLF13, MAML2, ETS1, HDAC1, NOTCH1, NOTCH2
Signaling by BMP	5	14.8×	0.001	BMP10, SMAD1, SMAD5, SMAD6, SMAD7
Pre-NOTCH Processing in the Endoplasmic Reticulum	3	47.2×	0.001	NOTCH1, NOTCH2, NOTCH4
Germ layer formation at gastrulation	4	22.2×	0.001	BMP4, CTNNB1, FOXH1, SMAD2
Formation of the nephric duct	4	21.0×	0.002	BMP4, CTNNB1, MECOM, OSR1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	3	40.5×	0.002	ADAM17, JAG1, NOTCH1
Molecules associated with elastic fibres	5	12.8×	0.002	BMP4, BMP10, FBLN2, FBN2, LTBP1
Mitotic Telophase/Cytokinesis	3	35.4×	0.003	SMC1A, SMC3, KIF20A
Transcriptional regulation of pluripotent stem cells	4	18.0×	0.003	FOXP1, CRIPTO, SALL4, SMAD2
Leishmania infection	6	8.1×	0.004	CDC42, ADAM17, CTSG, ABL1, MYO5A, PRKAR1B
Parasitic Infection Pathways	6	8.1×	0.004	CDC42, ADAM17, CTSG, ABL1, MYO5A, PRKAR1B
RUNX2 regulates osteoblast differentiation	4	15.1×	0.005	COL1A1, HEY1, HEY2, ABL1
NOTCH3 Intracellular Domain Regulates Transcription	4	14.5×	0.005	MAML2, HEY1, HEY2, NOTCH1
NOTCH1 Intracellular Domain Regulates Transcription	5	9.8×	0.005	MAML2, HDAC1, HEY1, HEY2, NOTCH1
Deactivation of the beta-catenin transactivating complex	5	9.6×	0.005	WDR5, BCL9, CTNNB1, HDAC1, KMT2D
Formation of paraxial mesoderm	4	13.5×	0.006	BMP4, MAML2, CTNNB1, NOTCH1
Regulation of signaling by NODAL	3	23.6×	0.007	CRIPTO, DAND5, LEFTY2
GP1b-IX-V activation signalling	3	23.6×	0.007	COL1A1, COL1A2, FLNA
Defective VWF binding to collagen type I	2	62.9×	0.009	COL1A1, COL1A2
RUNX2 regulates bone development	3	20.2×	0.009	SMAD1, SMAD6, ABL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 156 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	15	41.5×	6e-18	ROBO1, ROCK2, BMP4, TBX20, GATA5, ADAMTS19, NKX2-5, GATA4 (+7 more)
pulmonary valve morphogenesis	11	66.0×	9e-16	ROBO1, BMP4, ADAMTS19, HEY1, HEY2, JAG1, SMAD2, SMAD6 (+3 more)
ventricular septum morphogenesis	13	36.0×	9e-15	ROBO1, ACVR1, WNT11, ADAMTS19, ZFPM1, CITED2, NKX2-5, GJA5 (+5 more)
positive regulation of transcription by RNA polymerase II	45	4.3×	9e-15	ACVR1, BCL9, RXRA, BMP4, SRF, TCF21, VEGFA, MBTPS2 (+37 more)
cardiac conduction system development	10	67.5×	1e-14	SCN5A, CDC42, NKX2-5, GJA1, GJA5, HEY1, HEY2, SMAD1 (+2 more)
heart development	20	10.1×	3e-12	ACVR1, SRF, CRIPTO, ZFPM1, CITED2, NKX2-5, CC2D2A, FOXL1 (+12 more)
atrial septum morphogenesis	8	66.5×	2e-11	TBX20, ZFPM1, NKX2-5, GATA4, GJA5, HEY2, ISL1, NOTCH2
ventricular cardiac muscle tissue morphogenesis	9	40.5×	1e-10	BMP10, HAND1, ISL1, SMAD7, MYBPC3, MYH6, MYH7, MYL2 (+1 more)
heart looping	12	20.6×	1e-10	SRF, TBX20, CITED2, NKX2-5, MESP1, FGF8, FOXH1, GATA4 (+4 more)
outflow tract septum morphogenesis	9	37.4×	2e-10	ROBO1, LRP2, BMP4, TBX20, NKX2-5, FGF8, ISL1, SMAD6 (+1 more)
positive regulation of DNA-templated transcription	28	5.0×	3e-10	WDR5, ACVR1, RXRA, BMP4, WNT11, KAT6A, CITED2, BMP10 (+20 more)
outflow tract morphogenesis	11	21.6×	4e-10	VEGFA, WNT11, ZFPM1, CITED2, CTNNB1, FOXH1, GJA5, HAND2 (+3 more)
positive regulation of gene expression	23	5.7×	2e-09	ROBO1, ROCK2, BMP4, VEGFA, KAT6A, GATA5, CITED2, BMP10 (+15 more)
cardiac septum morphogenesis	7	54.0×	2e-09	CHD7, NKX2-5, HAND1, HEY1, HEY2, JAG1, NOTCH1
BMP signaling pathway	12	15.4×	2e-09	ACVR1, BMP4, CHRD, BMP10, LEFTY2, ETV2, SMAD1, SMAD5 (+4 more)
negative regulation of transcription by RNA polymerase II	32	3.6×	2e-08	WDR5, RXRA, BMP4, TBX20, TCF21, VEGFA, GATA5, ANKRD1 (+24 more)
secondary heart field specification	6	58.9×	3e-08	LRP2, BMP4, WNT11, MESP1, FOXH1, ISL1
branching involved in blood vessel morphogenesis	8	27.0×	4e-08	ACVR1, SRF, TBX20, VEGFA, CTNNB1, FGF8, NOTCH4, NRP1
cardiac right ventricle morphogenesis	6	54.0×	5e-08	TBX20, FOXH1, GATA4, HEY2, ISL1, JAG1
transcription by RNA polymerase II	16	7.2×	7e-08	KLF13, BCL9, BMP4, SRF, ASH1L, CHD7, NKX2-5, CTNNB1 (+8 more)
negative regulation of gene expression	16	7.1×	9e-08	ROBO1, FOXP1, ROCK2, BMP4, VEGFA, GATA5, CITED2, CTNNB1 (+8 more)
ureteric bud development	8	23.4×	1e-07	BMP4, TCF21, SMAD1, SMAD2, SMAD5, SMAD6, SMAD7, OSR1
adult heart development	6	46.3×	1e-07	CHD7, BMP10, NKX2-5, HAND2, MYH6, MYH7
embryonic hindlimb morphogenesis	7	26.1×	5e-07	BMP4, CHD7, CTNNB1, FGF8, MSX1, NOTCH1, OSR1
coronary artery morphogenesis	5	60.0×	6e-07	LRP2, VEGFA, HAND2, NOTCH1, NRP1
ventricular septum development	7	22.2×	2e-06	LRP2, SALL4, DAND5, GATA4, GJA5, HOXA13, SMAD6
atrioventricular canal development	5	49.1×	2e-06	TBX20, CHD7, GATA4, HAS2, PTPN11
pharyngeal system development	6	30.9×	2e-06	ACVR1, NKX2-5, NKX2-6, FGF8, ISL1, PTCH1
positive regulation of osteoblast differentiation	9	13.0×	2e-06	ACVR1, BMP4, VEGFA, CTNNB1, FBN2, JAG1, SMAD1, SMAD5 (+1 more)
embryonic heart tube development	6	29.5×	2e-06	CDC42, NKX2-5, CTNNB1, NKX2-6, GJA5, HAND1

Therapeutics

Drugs indicated for this disease

1 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bosentan	Approved (phase 4)
Allopurinol	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Dopamine	Phase 3 (in late-stage trials)
Gadobenate Dimeglumine	Phase 3 (in late-stage trials)
Gadopiclenol	Phase 3 (in late-stage trials)
Macitentan	Phase 3 (in late-stage trials)
Mannitol	Phase 3 (in late-stage trials)
Nitric Oxide	Phase 3 (in late-stage trials)
Norepinephrine	Phase 3 (in late-stage trials)
Tadalafil	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Arginine, Dexmedetomidine, Fibrinogen, Human, Levosimendan, Milrinone, Motavizumab, Nesiritide, Palivizumab, Phenoxybenzamine, Sevoflurane, Treprostinil, Tryptophan, Vasopressin.

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 16 · Phased (≥1): 16 · Undrugged: 67

Druggability breadth: 71 of 161 evidence-associated genes (44%) 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
SCN5A	BEPRIDIL
WDR5	ESOMEPRAZOLE
ACVR1	MOMELOTINIB
ROCK2	MOMELOTINIB
RXRA	BEXAROTENE
VEGFA	VADADUSTAT
ADAM17	PREDNISOLONE
GJA1	KANAMYCIN
HDAC1	CELECOXIB
NTRK3	FEDRATINIB
OSR1	VERTEPORFIN
PDGFRA	PONATINIB
PRKAB2	ADENOSINE PHOSPHATE
PRKD1	INGENOL MEBUTATE
KDM5A	DEFERASIROX

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN5A	108	4
PDGFRA	77	4
ROCK2	52	4
HDAC1	48	4
NTRK3	41	4
ACVR1	39	4
PRKD1	26	4
RXRA	23	4
ADAM17	8	4
WDR5	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	PDGFRA, SCN5A
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	ACVR1, NTRK3, PDGFRA, ROCK2, SCN5A
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 14.

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

Symbol	Assays	Type breakdown
HDAC1	3,675	Binding:3604, ADMET:57, Functional:13, Toxicity:1
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
RXRA	846	Binding:703, Functional:138, ADMET:5
ROCK2	788	Binding:783, Functional:3, ADMET:1, Toxicity:1
PRKD1	660	Binding:650, Functional:10
SCN5A	594	Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1
NTRK3	408	Binding:400, Functional:4, ADMET:4
PRKAB2	322	Binding:321, Functional:1
WDR5	314	Binding:311, Functional:3
ACVR1	299	Binding:293, Functional:4, ADMET:2
ADAM17	288	Binding:257, Functional:25, ADMET:5, Toxicity:1
KDM5A	165	Binding:165
BCL9	125	Binding:125
VEGFA	64	Binding:64
NRP1	50	Binding:50
OSR1	40	Binding:40
KCNJ2	31	Binding:23, ADMET:8
SMAD2	20	Binding:20
NFATC1	15	Binding:15
FMO5	14	ADMET:14
KIF20A	10	Binding:10
PCSK6	9	Binding:9
TLL1	5	Binding:5
COL1A2	4	Functional:4
GJA1	4	Binding:4
VCL	2	Binding:2
LRP2	1	Binding:1
SRF	1	Binding:1
CSRP1	1	Binding:1
PROX1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACVR1	2.7.10.2	non-specific protein-tyrosine kinase
RECQL4	3.6.4.12	DNA helicase
ADAM17	3.4.24.86	ADAM 17 endopeptidase
FMO5	1.14.13.8	flavin-containing monooxygenase
HAS2	2.4.1.212	hyaluronan synthase
HDAC1	3.5.1.98	histone deacetylase
ATE1	2.3.2.8	arginyltransferase
NTRK3	2.7.10.1	receptor protein-tyrosine kinase
PCSK6	3.4.21.61, 3.4.21.B25	Kexin,
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
PRKAB2	2.7.11.31	[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase
PRKD1	2.7.11.13	protein kinase C
KIF20A	5.6.1.3	plus-end-directed kinesin ATPase
KDM5A	1.14.11.67	[histone H3]-trimethyl-L-lysine4 demethylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN5A	594
WDR5	314
ACVR1	299
BCL9	125
ROCK2	788
RXRA	846
ADAM17	288
HDAC1	3,675
NTRK3	408
PDGFRA	1,172
PRKAB2	322
PRKD1	660
KDM5A	165

Pharmacogenomics

Cohort genes with a PharmGKB record: 83; 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)
BEPRIDIL	4	SCN5A
CANDESARTAN CILEXETIL	4	SCN5A
TELMISARTAN	4	SCN5A
CARBAMAZEPINE	4	SCN5A
DIBUCAINE	4	SCN5A
IMIPRAMINE	4	SCN5A
DROPERIDOL	4	SCN5A
PONATINIB	4	PDGFRA, SCN5A
DULOXETINE	4	SCN5A
PALONOSETRON	4	SCN5A
VILANTEROL	4	SCN5A
MEXILETINE HYDROCHLORIDE	4	SCN5A
UNOPROSTONE ISOPROPYL	4	SCN5A
LURASIDONE	4	SCN5A
LETERMOVIR	4	SCN5A
SERTINDOLE	4	SCN5A
FEDRATINIB	4	ACVR1, NTRK3, PDGFRA, ROCK2, SCN5A
QUINIDINE	4	SCN5A
DARUNAVIR	4	SCN5A
DARIFENACIN	4	SCN5A
BENZONATATE	4	SCN5A
TOLTERODINE	4	SCN5A
RANOLAZINE	4	SCN5A
PIMOZIDE	4	SCN5A
NIMODIPINE	4	SCN5A
FELODIPINE	4	SCN5A
NICARDIPINE	4	SCN5A
AMLODIPINE	4	SCN5A
PHENYTOIN	4	SCN5A
PALIPERIDONE	4	SCN5A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	SCN5A, WDR5, ACVR1, ROCK2, RXRA, VEGFA, ADAM17, GJA1, HDAC1, NTRK3 (+5 more)
B	Phased (≥1) drug, not yet approved	1	BCL9
C	Druggable family + PDB, no drug	8	ROBO1, RECQL4, TLL1, USP34, KCNJ2, MYBPC3, ATE1, KIF20A
D	Druggable family + AlphaFold only, no drug	6	ADAMTS19, USP44, FBLN2, FMO5, HAS2, PCSK6
E	Difficult family or no structure, no drug	53	KLF13, DCHS1, CRELD1, CTNNA3, DTNA, FOXP1, LRP2, RBFOX2, SRF, TBX20 (+43 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRELD1	0	GJA1
BMP10	0	ACVR1
GJA5	0	GJA1, SCN5A
ROBO1	0	—
KLF13	0	—
DCHS1	0	—
CTNNA3	0	—
DTNA	0	—
FOXP1	0	—
LRP2	1	—
RBFOX2	0	—
RECQL4	0	—
SRF	1	—
TBX20	0	—
TCF21	0	—
CRIPTO	0	—
TLL1	5	—
VCL	2	—
WNT11	0	—
ANKRD1	0	—
MAML2	0	—
RNF40	0	—
ADAMTS19	0	—
CHRD	0	—
ZFPM1	0	—
CITED2	0	—
USP44	0	—
USP34	0	—
COL1A2	4	—
SORBS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 679.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	588
PHASE2	29
PHASE3	15
PHASE1/PHASE2	13
PHASE4	12
PHASE2/PHASE3	11
PHASE1	8
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
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
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
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05101746	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Nitric Oxide Effect on Brain and Kidney in Pediatric Patients Undergoing Cardiopulmonary Bypass
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
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT00226369	PHASE2/PHASE3	COMPLETED	Cylexin for Reduction of Reperfusion Injury in Infant Heart Surgery
NCT00450684	PHASE2/PHASE3	COMPLETED	Cardiac Resynchronization Therapy in Congenital Heart Defects
NCT00945529	PHASE2/PHASE3	COMPLETED	The Effects of Inhaled Nitric Oxide After Fontan Operation
NCT01006629	PHASE2/PHASE3	COMPLETED	Palivizumab for Prevention of Severe Respiratory Syncytial Virus Infection in Russian Children
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
NCT02652741	PHASE2/PHASE3	UNKNOWN	Orodispersible Minitablets of Enalapril in Young Children With Heart Failure Due to Congenital Heart Disease
NCT02654678	PHASE2/PHASE3	UNKNOWN	Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
NCT03088345	PHASE2/PHASE3	COMPLETED	Early Use of Vasopressin in Post-Fontan Management
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
NCT03361189	PHASE2/PHASE3	TERMINATED	Specialized Pacing for Patients With Congenital Heart Disease
NCT04259684	PHASE2/PHASE3	WITHDRAWN	Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT05580510	PHASE2/PHASE3	UNKNOWN	Evaluation of Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan for CHF With Reduced Ejection Fraction in ACHD
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06080074	PHASE2	RECRUITING	Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System
NCT06882772	PHASE1/PHASE2	NOT_YET_RECRUITING	Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOSENTAN	4	4
DOPAMINE	4	3
PHENOXYBENZAMINE	4	3
THEOPHYLLINE ANHYDROUS	4	3
ALPROSTADIL	4	2
ILOPROST	4	2
MILRINONE	4	2
NITRIC OXIDE	4	2
PALIVIZUMAB	4	2
THIAMINE ION	4	2
TREPROSTINIL	4	2
BIVALIRUDIN	4	1
CEFAZOLIN	4	1
CEFOXITIN	4	1
FAMOTIDINE	4	1
GADOBENATE DIMEGLUMINE	4	1
GADOFOSVESET TRISODIUM	4	1
GADOPICLENOL	4	1
INDOMETHACIN	4	1
ISOFLURANE	4	1
LIOTHYRONINE SODIUM	4	1
MACITENTAN	4	1
NESIRITIDE	4	1
NOREPINEPHRINE	4	1
OXANDROLONE	4	1
PORACTANT ALFA	4	1
SODIUM BICARBONATE	4	1
SOTATERCEPT	4	1
TRANEXAMIC ACID	4	1
VASOPRESSIN	4	1