Table 2

Common congenital heart disease resulting from single gene defects

GeneLocusProteinCardiac phenotypeOMIM
Gene associated with transcription factors of cardiac developmentGATA48p23.1GATA4 transcription factorASD, VSD, AVSD, PS, PAPVR and TOF.600 576
GATA520q13.33GATA5 transcription factorCongenital bicuspid aortic valve and VSD.617 912
GATA618q11.2GATA6 transcription factorASD, VSD, AVSD, OFT defects, PDA, PS and TOF.601 656
NKX2.55q35.1Homeobox containing transcription factorASD, VSD, TOF, HLHS, CoA, TGA, DORV, IAA and OFT defects.600 584
NKX2.68p21.2Homeobox containing transcription factorPTA and conotruncal heart malformations.217 095
TBX122q11.2T-Box 1 transcription factorTOF.602 054
TBX512q24.21T-Box 5 transcription factorASD, VSD and AVSD.601 620
TBX207p14.2T-Box 20 transcription factorASD, VSD and MS.611 363
TFAP2β6p12.3Transcription factor AP-2 betaPDA.601 601
ZIC3Xq26.3Zinc finger transcription factorASD, VSD, HLHS, DORV, PS, TGA, TAPVR, dextrocardia, L-R axis defects and heterotaxy.300 265
Gene associated with signaling pathways of cardiac developmentAXIN217q24.1Axin-related protein 2Congenital valve defect./
BRAF7q34Serine/threonine-protein kinase B-rafASD, and PAS.164 757
CBL11q23.3E3 ubiquitin-protein ligase CBLAVSD, HCM and PS.613 563
DLL415q15.1Delta-like protein 4Left-sided obstructive lesions, septal and conotruncal defects and tricuspid atresia.616 589
FOXH18q24.3Forkhead box protein H1TOF and TGA./
GALNT117q36.1Polypeptide N-acetylgalactosaminyltransferase 11Heterotaxy./
GLI112q13.3Zinc finger protein GLI1Abnormity of atrioventricular separation and cardiac OFT.165 220
HHEX10q23.33Hematopoietically expressed homeoboxVentricular aplasia, dense myocardial dysplasia and intracardiac membrane dysplasia./
HRAS11p15.5GTPase HRasPAS and tachycardia.190 020
JAG120p12.2Protein Jagged-1PAS and TOF.601 920
KRAS12p12.1GTPase KRasASD and PAS.190 070
MAML15q35.3Mastermind-like protein 1Aortic valve disease./
MEK115q22.31Dual specificity mitogen-activated protein kinase kinase 1ASD and PAS.176 872
MEK219p13.3Dual specificity mitogen-activated protein kinase kinase 2ASD and PAS.601 263
NOTCH19q34.3Notch receptor 1Aortic valve disease.190 198
NOTCH21p12Notch receptor 2AS, TOF and PAS.610 205
NRAS1p13.2GTPase NRasHCM and PS.164 790
PPP1CB2p23.2Serine/threonine-protein phosphatase PP1-beta catalytic subunitASD, VSD, HCM, PAS and TOF.617 506
PTPN1112q24.13Protein tyrosine phosphatase non-receptor type 11ASD, VSD and PAS.176 876
RAF13p25.2RAF proto-oncogene serine/threonine-protein kinaseASD and TOF.164 760
RIT11q22GTP-binding protein Rit1VSD, TOF and PAS.615 355
SHOC210q25.2Leucine-rich repeat protein SHOC-2ASD, VSD, HCM, PAS and TOF.607 721
SMAD615q22.31Mothers against decapentaplegic-related protein 6AV disease.602 931
SOS12p22.1Son of sevenless homolog 1ASD, VSD and TOF.182 530
SOS214q21.3Son of sevenless homolog 2ASD, VSD and TOF.616 559
TGF-β119q13.2Transforming growth factor beta-1 proproteinCoA, HLHS, BAV and AS./
Gene associated with structural proteins of cardiac developmentACTC15q14Alpha cardiac actinASD.102 540
ELN7q11.23ElastinAS, PAS, PS and SVAS.130 160
MYH614q11.2Alpha myosin heavy chainAS, ASD, PFO, TA and TGA.160 710
MYH714q11.2Beta myosin heavy chainASD, NVM and Ebstein anomaly.160 760
MYH1116p13.11Myosin heavy chain 11Aortic aneurysm and PDA.132 900
  • AS, aortic stenosis; ASD, atrial septal defect; AV, aortic valve; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CoA, coarctation of the aorta; DORV, double outlet right ventricle; HCM, hypertrophic cardiomyopathy; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; L-R, Left-right; MS, mitral stenosis; NVM, non-compaction of ventricular myocardium; OFT, outflow tract; OMIM, online mendelian inheritance in man; PAPVR, partial anomalous pulmonary venous return; PAS, pulmonary artery stenosis; PDA, patent ductus arteriosus; PFO, patent foramen ovale; PS, pulmonary (valve) stenosis; PTA, persistent truncus arteriosus; SVAS, supravalvar aortic stenosis; TA, tricuspid atresia; TAPVR, total anomalous pulmonary venous return; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; VSD, ventricular septal defect.