Table 2.
Genes Involved in Syndromic and Non-Syndromic Cardiovascular Malformations in Humans
| Class | OMIM | Gene | Disorder or Syndrome | Heart Defects |
|---|---|---|---|---|
| 136760 | ALX3 | Frontonasal Dysplasia 1 | TOF | |
| Transcription Factor | 300215 | ARX | Lissencephaly, X-Linked, With Ambiguous Genitalia | VSD, PDA |
| 602937 | CITED2 | Isolated septal defect | ASD, VSD | |
| 225500 | EVC, EVC2 | Ellis-Van Creveld | Common atrium, AVSD, HLHS | |
| 166780 | EYA1 | Otofaciocervical Syndrome | TOF | |
| FOXC1 | Axenfeld-Rieger Syndrome, Type 3 | PDA, ASD, AS, MR | ||
| 153400 | FOXC2 | Lymphedema-Distichiasis | TOF, VSD, TAPVR | |
| 265380 | FOXF1-FOXC2-FOXL1 deletion | Alveolar Capillary Dysplasia With Misalignment Of Pulmonary Veins | APVR, HLHS | |
| 607941 | GATA4 | Familial ASD2 | ASD | |
| 200990 | GLI3 | Acrocallosal, Pallister-Hall | VSD, PS, ASD | |
| 601536 | HOXA1 | Athabaskan Brainstem Dysgenesis | TOF | |
| 169400 | LBR | Pelger-Huet Anomaly | VSD | |
| 309520 | MED12 | Lujan-Fryns Syndrome | ASD, VSD, aortic aneurysm | |
| 164280 | MYCN | Feingold | PDA | |
| 108900 | NKX2.5 | ASD with Conduction Defect | ASD, TOF, Dextrocardia | |
| 148820 | PAX3 | Waardenburg Type III | ASD | |
| 107480 | SALL1 | Townes-Brocks | VSD, TOF | |
| 607323 | SALL4 | Duane Radial Ray | VSD | |
| 269150 | SETBP1 | Schinzel-Giedion Midface Retraction Syndrome | ASD | |
| 212550 | SIX6 | Microphthalmia, Isolated, With Cataract Type 2 | VSD, PDA | |
| 601349 | SNX3 | Microcephaly, Microphthalmia, Ectrodactyly Of Lower Limbs, And Prognathism | VSD | |
| 206900 | SOX2 | Microphthalmia And Esophageal Atresia | VSD, PDA | |
| 114290 | SOX9 | Campomelic Dysplasia | Complex | |
| 602054 | TBX1 | DiGeorge, Conotruncal Anomaly Face | TOF, PA, IAA(B), RAA, DORV VSD, TA | |
| 181450 | TBX3 | Ulnar-Mammary | PS | |
| 142900 | TBX5 | Holt-Oram | VSD, ASD, HLHS, TAPVR, TOF, DORV | |
| 611363 | TBX20 | Familial ASD4 | ASD | |
| 169100 | TFAP2B | Char | PDA, muscular VSD | |
| 608771 | THRAP2, ZIC3 | Transposition of the Great Arteries | TGA | |
| 106260 | TP73L | Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate | VSD, PDA | |
| 101400 | TWIST | Saethre-Chotzen | VSD | |
| 235730 | ZFHX1B | Mowat-Wilson | VSD, PDA | |
| 603693 | ZFPM2/FOG2 | Tetralogy of Fallot | TOF | |
| 306955 | ZIC3 | Heterotaxy 1, X-linked | Dextrocardia, TGA, PS, VSD, TAPVR, HLHS, CoA | |
| 301040 | ATRX | Alpha-Thalassemia/Mental Retardation, X-Linked | VSD | |
| Chromatin Regulator | 214800 | CHD7 | CHARGE | TOF, IAA(B), VSD, DORV+/−AVSD, TA |
| 180849 | CREBBP | Rubenstein-Taybi | VSD, ASD, PDA, CoA, HLHS | |
| 268300 | ESCO2 | Roberts, SC Phocomelia | PS, PA | |
| 147920 | MLL2 | Kabuki | CoA, VSD, ASD | |
| 275210 | LMNA | Lethal Tight Skin Contracture | PDA, ASD | |
| 300000 | MID1 | Opitz | VSD, Persistent LSVC, ASD, PDA, DORV | |
| 122470 | NIPBL | Brachman-De Lange | BAV, VSD, PS | |
| 117550 | NSD1 | Sotos | ASD, VSD, PDA | |
| 309500 | PQBP1 | Renpenning | ASD, Dextrocardia | |
| 218600 | RECQL4 | Baller-Gerold | VSD, ASD | |
| 273395 | ZMPSTE24 | Tetra-Amelia | PDA, ASD | |
| 602730 | ACVR2B | Heterotaxy | HLHS, AVSD, LSVC | |
| 149000 | AGGF1 | Klippel-Trenaunay-Weber | PDA, ASD, PS, MVP | |
| 300166 | BCOR | Microphthalmia, syndromic Type 2 | ASD, VSD, MVP | |
| 178600 | BMPR2 | Primary Pulmonary Hypertensions with CHD | AVSD, ASD, VSD, PDA, PAPVR | |
| 605376 | CFC1 | Heterotaxy 2 | DORV, TA, TGA, Heterotaxy | |
| 277300 | DLL3 | Jarcho-Levin | ASD, DORV | |
| 305400 | FGD1 | Aarskog-Scott | ASD, VSD, PS, AS, CoA | |
| 207410 | FGFR2 | Antley-Bixler | ASD | |
| 101200 | FGFR2 | Apert | VSD | |
| 187500 | JAG1, GDF1 | Tetralogy of Fallot | TOF | |
| 218040 | HRAS | Costello | HCM, PS, ASD, other valve dysplasia, dysrhythmias | |
| 300472 | IGBP1 | Corpus Callosum, Agenesis Of, With Mental Retardation, Ocular Coloboma, and Micrognathia | VSD, PDA | |
| Ligand, Receptor, Signal Transduction | 118450 | JAG1, NOTCH2 | Alagille | TOF+/−PA, CoA, PS, ASD, VSD |
| 115150 | KRAS, BRAF, MEK1, MEK2 | Cardiofaciocutaneous | ASD, PS, HCM | |
| 601877 | LEFTY2 | Heterotaxy | Heterotaxy, HLHS, AVSD, LSVC | |
| 259770 | LRP5 | Osteoporosis-Pseudoglioma Syndrome | VSD | |
| 162200 | NF1 | Neurofibromatosis-Noonan, Watson | PS, VSD, CoA | |
| 109198 | NOTCH1 | Familial Calcific Bicuspid Aortic Valve | BAV, MS, VSD, TOF | |
| 194200 | PRKAG2 | Wolff-Parkinson-White | Accessory Conduction Pathways | |
| 255960 | PRKAR1A | Intracardiac Myxoma | ASD | |
| 153480 | PTEN | Bannayan-Zonana | ASD | |
| 163950 | PTPN11, KRAS, SOS1, RAF1, NRAS, BRAF, SHOC2, CBL, NF1 | Noonan, LEOPARD | PS, HCM, CoA, ASD | |
| 268310 | ROR2 | Robinow, Brachydactyly Type B1 | PS, PA | |
| 609192 | TGFBR2, TGFBR1 | Loeys-Dietz | PDA, ASD, BAV | |
| 243800 | UBR1 | Johanson-Blizzard | ASD, VSD, Dextrocardia | |
| 300373 | WTX | Osteopathia Striata With Cranial Sclerosis | ASD, VSD, PDA | |
| 235510 | CCBE1 | Hennekam Lymphangiectasia-Lymphedema Syndrome | ASD, VSD, pericardial lymphangiectasia and effusion | |
| 267750 | COL18A1 | Knobloch | PDA, VSD, TAPVR | |
| 200610 | COL2A1 | Achondrogenesis Type II | ASD, AVSD | |
| 606217 | CRELD1 | AVSD2 | AVSD, Heterotaxy, PA | |
| 606617 | DTNA | Left Ventricular Noncompaction | LSVC, PDA, HLHS | |
| Structural, or Cell Adhesion | 185500 | ELN1 | Familial Supravalvar Aortic Stenosis | SVAS |
| 608328 | FBN1, ADAMTS10 | Weill-Marchesani | AS, MI, PS, PDA, VSD | |
| 121050 | FBN2 | Congenital Contractural Arachnodactyly | ASD, VSD | |
| 309350 | FLNA | Melnick-Needles | TOF | |
| 150250 | FLNB | Larsen | ASD, VSD | |
| 312870 | GPC3 | Simpson-Golabi-Behmel | VSD, PS, TGA, PDA, HCM | |
| 607941 | MYH6 | Familial ASD | ASD | |
| MYH11 | Familial Thoracic Aortic Aneurysm with PDA | PDA | ||
| 612794 | ACTC1 | Familial ASD5 | ASD | |
| 608688 | ATIC | IMP Cyclohydrolase Deficiency | ASD | |
| 261540 | B3GALTL | Peters Plus Syndrome | ASD, VSD, subvalvar AS, PS, BAV | |
| Metabolic | 602398 | DHCR24 | Desmosterolosis | TAPVR, PDA |
| 270400 | DHCR7 | Smith-Lemli-Opitz | AVSD, ASD, VSD, PDA, HLHS, CoA, PS, TAPVR | |
| 608799 | DPM1 | Congenital Disorder Of Glycosylation Type 1e | PDA | |
| 612541 | G6PC3 | Neutropenia, severe congenital, autosomal recessive 4 | ASD | |
| 309801 | HCCS | Microphthalmia, Syndromic 7; MCOPS7 | ASD, VSD, cardiomyopathy | |
| 212066 | MGAT | Congenital Disorder of Glycosylation, type IIa | VSD | |
| 308050 | NSDHL | Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects | ASD, VSD, Single ventricle, CoA, Shone Complex | |
| 214100 | PEX genes | Zellweger | VSD, PDA, HLHS | |
| 201000 | RAB23 | Carpenter Syndrome | ASD, VSD, TOF, PS, TGA, PDA | |
| 208085 | VPS33B | Arthrogryposis, renal dysfunction, and cholestasis type 1 | ASD, VSD | |
| 601005 | CACNA1C | Timothy | VSD, TOF, PDA, Long QT | |
| Ion Channel | 170390 | KCNJ2 | Andersen | BAV, CoA, Long QT |
| 612391 | SLC29A3 | Hyperpigmentation, cutaneous, with hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism with or without hearing loss | ASD, VSD, BAV, MVP | |
| 227650 | FANC genes | Fanconi | VSD, TOF | |
| DNA Repair | ||||
| 209900 | BBS1,-2,-4,-5,-9,-10,-12; ARL6, BBS4, BBS5, MKKS, TTC8, TRIM32, MKS1, CEP290, C2ORF86, CCDC28B | Bardet-Biedl | VSD, Dextrocardia | |
| Monocilia | 270100 | DNAH11, DNAI1, DNAH5 | Situs Inversus Viscerum, Kartegener | TGA, TA, VSD, ASD |
| 604896 | MKKS | McKusick-Kaufman | TOF | |
| 249000 | MKS1 | Meckel | ASD, VSD, CoA, PDA | |
| 208540 | NPHP3 | Renal-Hepatic-Pancreatic Dysplasia | Dextrocardia, ASD, AS | |
| 105650 | RPS19 | Diamond-Blackfan Anemia | VSD | |
| RNA Binding | 300080 | RBM10 | TARPS syndrome | ASD |
| Cell Cycle | 300707 | FAM58A | STAR Syndrome | ASD, VSD |
*
ASD – atrial septal defect, primum or secundum; AS – aortic stenosis; AVSD – atrioventricular septal defect; BAV – bicuspid aortic valve; CoA – coarctation of the aorta; DCM – dilated cardiomyopathy; DORV double outlet right ventricle; HCM – hypertrophic cardiomyopathy; HLHS – hypoplastic left heart; IAA(B) – interrupted aortic arch type B; LSVC – persistent left superior vena cava; MVP – mitral valve prolapse; PA – pulmonary atresia; PDA – patent ductus arteriosus; PPAS – peripheral pulmonary artery stenosis; PS - pulmonic stenosis; Shone complex – parachute mitral valve, aortic stenosis, coarctation; SVAS – supravalvar aortic stenosis; TA – truncus arteriosus; TAPVR – total anomalous pulmonary venous return; TOF – tetralogy of Fallot; VSD – ventricular septal defect