Details of Disease

Disease Name

Ventricular septal defect

ventricular septal defects; heart septal defects, ventricular; ventricular septal defect (disease); ventricular septal defect; ventricular septal abnormality; interventricular septal defect; interventricular communication; VSD

Definition

The presence of a defect (opening) in the septum that separates the two ventricles of the heart. It can be congenital or acquired.

Disease Hierarchy

DISQ5C5J: Heart septal defect

DISMT2VZ: Cardiogenetic disease

DISICO41: Ventricular septal defect

Disease Identifiers

MONDO ID

MONDO_0002070

MESH ID

D006345

UMLS CUI

C0018818

MedGen ID

42366

HPO ID

HP:0001629

Orphanet ID

1480

SNOMED CT ID

253549006

General Information of Disease (ID: DISICO41)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EPO	TTQG4NR	Limited	Biomarker	[1]
OPRD1	TT27RFC	Limited	Biomarker	[2]
PCSK5	TTPFWHU	Limited	Biomarker	[3]
GJA1	TT4F7SL	Disputed	Genetic Variation	[4]
ROR2	TTUDPCI	moderate	Genetic Variation	[5]
SCN4A	TT84DRB	moderate	CausalMutation	[6]
CPB1	TT4UJX5	Strong	Altered Expression	[7]
EP300	TTGH73N	Strong	Altered Expression	[8]
GLI1	TTJOMH6	Strong	Genetic Variation	[9]
GPC3	TTJTSX4	Strong	Biomarker	[10]
IGF1R	TTQFBMY	Strong	Altered Expression	[11]
MYBPC3	TT9WOBN	Strong	Genetic Variation	[12]
MYH7	TTNIMDP	Strong	Genetic Variation	[13]
NTRK3	TTXABCW	Strong	Biomarker	[14]
YES1	TT0SQ8J	Strong	Biomarker	[15]
------------------------------------------------------------------------------------


⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A5	DTL1TRY	Strong	Genetic Variation	[16]
------------------------------------------------------------------------------------

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHDH	DEAHED0	Strong	Biomarker	[17]
MTRR	DE6NIY9	Strong	Genetic Variation	[18]
------------------------------------------------------------------------------------

This Disease Is Related to 51 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CITED2	OT812TV7	Limited	Biomarker	[8]
IRX4	OT0TV6WK	Limited	Biomarker	[19]
MATR3	OTESJ5S7	Limited	Biomarker	[20]
NKX2-5	OTS1SAWM	Limited	Biomarker	[21]
NOX5	OTHTH59G	Limited	Biomarker	[22]
TBX3	OTM64N7K	Disputed	Genetic Variation	[23]
SALL4	OTC08PR5	moderate	Biomarker	[24]
SOS1	OTTCWXC3	moderate	CausalMutation	[25]
ACTC1	OTJU04B1	Strong	Biomarker	[26]
ADO	OTRLGQ7V	Strong	Biomarker	[27]
ARSD	OTAHW9M8	Strong	Genetic Variation	[28]
ARSH	OTG0X9UQ	Strong	Biomarker	[29]
CAMK2A	OTJGX19T	Strong	CausalMutation	[30]
CASZ1	OTWJ2OR8	Strong	Genetic Variation	[31]
CRELD1	OTBSPZFP	Strong	Genetic Variation	[32]
DARS1	OT0WGC2T	Strong	Genetic Variation	[33]
DNTT	OTFSEF12	Strong	Biomarker	[34]
DVL3	OTPRROHJ	Strong	Biomarker	[35]
EVC	OTRVYMXJ	Strong	Genetic Variation	[36]
FOXH1	OTEXJ9SL	Strong	Genetic Variation	[37]
GATA5	OTO81B63	Strong	Genetic Variation	[38]
GATA6	OTO2BC0F	Strong	Genetic Variation	[39]
HAND1	OTN4IPVV	Strong	Genetic Variation	[40]
HEY2	OTU4J3ZI	Strong	Biomarker	[41]
HMGN1	OTSMGH99	Strong	Biomarker	[42]
HOMEZ	OTODFO9P	Strong	Genetic Variation	[43]
HOXB1	OTGC0EKI	Strong	Biomarker	[44]
KLF13	OTMIKHZ4	Strong	Genetic Variation	[45]
KMT2D	OTTVHCLY	Strong	CausalMutation	[46]
LEFTY2	OT3RX4QF	Strong	Altered Expression	[8]
LRPAP1	OT6DVD2Q	Strong	Genetic Variation	[47]
MEIS2	OTG4ADLM	Strong	Genetic Variation	[48]
MESP1	OTY5QDBN	Strong	Genetic Variation	[49]
NR2F2	OTJFS67N	Strong	Genetic Variation	[50]
PFKL	OTVHGAT7	Strong	Biomarker	[51]
PLAGL1	OTZAO900	Strong	Genetic Variation	[52]
REC8	OT6JAVXE	Strong	Genetic Variation	[53]
RERE	OT3G4GBZ	Strong	Biomarker	[54]
SENP2	OTPQJXIR	Strong	Altered Expression	[55]
SOX4	OTSS40SS	Strong	Genetic Variation	[56]
SSPN	OTYG2SL7	Strong	Genetic Variation	[21]
STPG4	OT5K4UFL	Strong	CausalMutation	[46]
TBX1	OTQLBPRA	Strong	Genetic Variation	[57]
TBX18	OT3BEBLN	Strong	Genetic Variation	[58]
TBX2	OTTOT7A9	Strong	Biomarker	[59]
TNXB	OTVBWAV5	Strong	Genetic Variation	[60]
TRDN	OTXVE9SF	Strong	Biomarker	[12]
TSHZ1	OTYQ9ECW	Strong	Genetic Variation	[61]
TTC7A	OTDHLPQM	Strong	CausalMutation	[46]
ISL1	OTVNVKAX	Definitive	Genetic Variation	[62]
TBX20	OTMPU2XQ	Definitive	Genetic Variation	[63]
------------------------------------------------------------------------------------


⏷ Show the Full List of 51 DOT(s)

References

1	Cardiogenic shock complicating myocardial infarction in a doped athlete.Acute Card Care. 2009;11(4):250-1. doi: 10.1080/17482940902842564.
2	Effects of Prenatal PM(10) Exposure on Fetal Cardiovascular Malformations in Fuzhou, China: A Retrospective Case-Control Study.Environ Health Perspect. 2017 May 25;125(5):057001. doi: 10.1289/EHP289.
3	VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5.Genes Dev. 2008 Jun 1;22(11):1465-77. doi: 10.1101/gad.479408.
4	The role of intraoperative epicardial echocardiography in pediatric cardiac surgery.Echocardiography. 2018 Jul;35(7):999-1004. doi: 10.1111/echo.13874. Epub 2018 Mar 25.
5	Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B. Am J Hum Genet. 2000 Oct;67(4):822-31. doi: 10.1086/303084. Epub 2000 Sep 12.
6	[The construction and preliminary investigation of the cell model of a novel mutation R675Q in the SCN4A gene identified in a Chinese family with normokalemic periodic paralysis].Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Dec;25(6):629-32.
7	Changes in the levels of inflammatory markers after transthoracic device closure of ventricular septal defects in pediatric patients.J Cardiothorac Surg. 2019 Apr 8;14(1):70. doi: 10.1186/s13019-019-0900-4.
8	Down-regulation of EBAF in the heart with ventricular septal defects and its regulation by histone acetyltransferase p300 and transcription factors smad2 and cited2.Biochim Biophys Acta. 2013 Dec;1832(12):2145-52. doi: 10.1016/j.bbadis.2013.07.013. Epub 2013 Jul 27.
9	Association of the GLI gene with ventricular septal defect after the susceptibility gene being narrowed to 3.56 cM in 12q13.Chin Med J (Engl). 2006 Feb 20;119(4):267-74.
10	Loss of glypican-3 function causes growth factor-dependent defects in cardiac and coronary vascular development.Dev Biol. 2009 Nov 1;335(1):208-15. doi: 10.1016/j.ydbio.2009.08.029. Epub 2009 Sep 4.
11	Down regulation of IGF-I and IGF-IR gene expression in right atria tissue of ventricular septal defect infants with right atria hypoxemia.Clin Chim Acta. 2007 Apr;379(1-2):81-6. doi: 10.1016/j.cca.2006.12.021. Epub 2007 Jan 10.
12	Efficient Mining of Variants From Trios for Ventricular Septal Defect Association Study.Front Genet. 2019 Aug 8;10:670. doi: 10.3389/fgene.2019.00670. eCollection 2019.
13	Familial ebstein anomaly, left ventricular hypertrabeculation, and ventricular septal defect associated with a MYH7 mutation. Am J Med Genet A. 2013 Dec;161A(12):3187-90. doi: 10.1002/ajmg.a.36182. Epub 2013 Aug 16.
14	Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease.Hum Mutat. 2014 Dec;35(12):1459-68. doi: 10.1002/humu.22688. Epub 2014 Nov 7.
15	Deletion of yes-associated protein (YAP) specifically in cardiac and vascular smooth muscle cells reveals a crucial role for YAP in mouse cardiovascular development.Circ Res. 2014 Mar 14;114(6):957-65. doi: 10.1161/CIRCRESAHA.114.303411. Epub 2014 Jan 29.
16	UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients.Am J Med Genet A. 2010 Dec;152A(12):3084-90. doi: 10.1002/ajmg.a.33743.
17	Early Experience of Macitentan for Pulmonary Arterial Hypertension in Adult Congenital Heart Disease.Heart Lung Circ. 2017 Oct;26(10):1113-1116. doi: 10.1016/j.hlc.2016.12.011. Epub 2017 Feb 6.
18	Analysis of MTR and MTRR Gene Polymorphisms in Chinese Patients With Ventricular Septal Defect.Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):769-774. doi: 10.1097/PAI.0000000000000512.
19	Two novel mutations of the IRX4 gene in patients with congenital heart disease. Hum Genet. 2011 Nov;130(5):657-62. doi: 10.1007/s00439-011-0996-7. Epub 2011 May 5.
20	MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.Hum Mol Genet. 2015 Apr 15;24(8):2375-89. doi: 10.1093/hmg/ddv004. Epub 2015 Jan 7.
21	Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart.Sci Rep. 2017 Apr 13;7:46438. doi: 10.1038/srep46438.
22	Regulation of NADPH oxidase 5 by protein kinase C isoforms.PLoS One. 2014 Feb 5;9(2):e88405. doi: 10.1371/journal.pone.0088405. eCollection 2014.
23	Genetic analysis of the TBX3 gene promoter in ventricular septal defects.Gene. 2013 Jan 10;512(2):185-8. doi: 10.1016/j.gene.2012.10.066. Epub 2012 Oct 29.
24	Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
25	SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.Hum Mutat. 2011 Jul;32(7):760-72. doi: 10.1002/humu.21492. Epub 2011 Apr 28.
26	The NFKB1 -94 ATTG insertion/deletion polymorphism (rs28362491) contributes to the susceptibility of congenital heart disease in a Chinese population.Gene. 2013 Mar 10;516(2):307-10. doi: 10.1016/j.gene.2012.12.078. Epub 2013 Jan 5.
27	Treatment of congenital non-ductal shunt lesions with the amplatzer duct occluder II.Catheter Cardiovasc Interv. 2017 May;89(6):E185-E193. doi: 10.1002/ccd.25250. Epub 2013 Nov 18.
28	A New Perspective of Migraine Symptoms in Patients With Congenital Heart Defect.Headache. 2018 Nov;58(10):1601-1611. doi: 10.1111/head.13453. Epub 2018 Nov 16.
29	Congenital heart malformations associated with disproportionate ventricular septal thickening.Circulation. 1975 Nov;52(5):926-32. doi: 10.1161/01.cir.52.5.926.
30	De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet. 2017 Nov 2;101(5):768-788. doi: 10.1016/j.ajhg.2017.10.003.
31	A novel de novo CASZ1 heterozygous frameshift variant causes dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy.Mol Genet Genomic Med. 2019 Aug;7(8):e828. doi: 10.1002/mgg3.828. Epub 2019 Jul 3.
32	Germline mutations in NKX2-5, GATA4, and CRELD1 are rare in a Mexican sample of Down syndrome patients with endocardial cushion and septal heart defects.Pediatr Cardiol. 2015 Apr;36(4):802-8. doi: 10.1007/s00246-014-1091-3. Epub 2014 Dec 19.
33	Association of DARS gene polymorphisms with the risk of isolated ventricular septal defects in the Chinese Han population.Ital J Pediatr. 2016 Nov 21;42(1):102. doi: 10.1186/s13052-016-0311-2.
34	VEGF C-634G polymorphism is associated with protection from isolated ventricular septal defect: case-control and TDT studies.Eur J Hum Genet. 2007 Dec;15(12):1246-51. doi: 10.1038/sj.ejhg.5201890. Epub 2007 Jul 11.
35	Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes.Development. 2012 Dec 1;139(23):4383-94. doi: 10.1242/dev.083352. Epub 2012 Oct 24.
36	Molecular mechanisms of Ellisvan Creveld gene variations in ventricular septal defect.Mol Med Rep. 2018 Jan;17(1):1527-1536. doi: 10.3892/mmr.2017.8088. Epub 2017 Nov 15.
37	Forkhead box H1 (FOXH1) sequence variants in ventricular septal defect.Int J Cardiol. 2010 Nov 5;145(1):83-5. doi: 10.1016/j.ijcard.2009.05.030. Epub 2009 Jun 13.
38	Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects.World J Pediatr. 2014 Nov;10(4):348-53. doi: 10.1007/s12519-014-0511-z. Epub 2014 Dec 17.
39	Novel and functional DNA sequence variants within the GATA6 gene promoter in ventricular septal defects.Int J Mol Sci. 2014 Jul 17;15(7):12677-87. doi: 10.3390/ijms150712677.
40	HAND1 loss-of-function mutation contributes to congenital double outlet right ventricle.Int J Mol Med. 2017 Mar;39(3):711-718. doi: 10.3892/ijmm.2017.2865. Epub 2017 Jan 20.
41	A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect.Pediatr Cardiol. 2019 Jun;40(5):1084-1091. doi: 10.1007/s00246-019-02099-y. Epub 2019 Apr 6.
42	Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome?.Hum Genet. 2000 Nov;107(5):476-82. doi: 10.1007/s004390000395.
43	Identification of two novel mutations of the HOMEZ gene in Chinese patients with isolated ventricular septal defect.Genet Test Mol Biomarkers. 2013 May;17(5):390-4. doi: 10.1089/gtmb.2012.0435. Epub 2013 Apr 10.
44	Analysis of HOXB1 gene in a cohort of patients with sporadic ventricular septal defect.Mol Biol Rep. 2018 Oct;45(5):1507-1513. doi: 10.1007/s11033-018-4212-x. Epub 2018 Jun 19.
45	KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5.Hum Mol Genet. 2017 Mar 1;26(5):942-954. doi: 10.1093/hmg/ddx009.
46	A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.
47	Isolation of differentially expressed genes in human heart tissues.Biochim Biophys Acta. 2002 Dec 12;1588(3):241-6. doi: 10.1016/s0925-4439(02)00171-0.
48	De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities, developmental delay, intellectual disability and dysmorphic features.Am J Med Genet A. 2018 Sep;176(9):1845-1851. doi: 10.1002/ajmg.a.40368. Epub 2018 Jul 28.
49	MESP1 lossoffunction mutation contributes to double outlet right ventricle.Mol Med Rep. 2017 Sep;16(3):2747-2754. doi: 10.3892/mmr.2017.6875. Epub 2017 Jun 29.
50	A novel NR2F2 loss-of-function mutation predisposes to congenital heart defect.Eur J Med Genet. 2018 Apr;61(4):197-203. doi: 10.1016/j.ejmg.2017.12.003. Epub 2017 Dec 6.
51	Down syndrome congenital heart disease: a narrowed region and a candidate gene.Genet Med. 2001 Mar-Apr;3(2):91-101. doi: 10.1097/00125817-200103000-00002.
52	A novel variation of PLAGL1 in Chinese patients with isolated ventricular septal defect.Genet Test Mol Biomarkers. 2012 Aug;16(8):984-7. doi: 10.1089/gtmb.2012.0003. Epub 2012 Jul 11.
53	San Luis Valley recombinant chromosome 8 and tetralogy of Fallot: a review of chromosome 8 anomalies and congenital heart disease.Am J Med Genet. 1991 Sep 15;40(4):471-6. doi: 10.1002/ajmg.1320400420.
54	RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects.Dis Model Mech. 2018 Aug 28;11(9):dmm031534. doi: 10.1242/dmm.031534.
55	Enhanced desumoylation in murine hearts by overexpressed SENP2 leads to congenital heart defects and cardiac dysfunction.J Mol Cell Cardiol. 2012 Mar;52(3):638-49. doi: 10.1016/j.yjmcc.2011.11.011. Epub 2011 Dec 1.
56	De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. Am J Hum Genet. 2019 Feb 7;104(2):246-259. doi: 10.1016/j.ajhg.2018.12.014. Epub 2019 Jan 17.
57	TBX1 loss-of-function mutation contributes to congenital conotruncal defects.Exp Ther Med. 2018 Jan;15(1):447-453. doi: 10.3892/etm.2017.5362. Epub 2017 Oct 24.
58	Novel and functional variants within the TBX18 gene promoter in ventricular septal defects.Mol Cell Biochem. 2013 Oct;382(1-2):121-6. doi: 10.1007/s11010-013-1725-4. Epub 2013 Jun 8.
59	Novel and functional sequence variants within the TBX2 gene promoter in ventricular septal defects.Biochimie. 2013 Sep;95(9):1807-9. doi: 10.1016/j.biochi.2013.05.007. Epub 2013 May 28.
60	Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal Defects.Mol Diagn Ther. 2018 Apr;22(2):235-240. doi: 10.1007/s40291-018-0321-4.
61	Analysis of RTN4 3'UTR insertion/deletion polymorphisms in ventricular septal defect in a Chinese Han population.DNA Cell Biol. 2011 May;30(5):323-7. doi: 10.1089/dna.2010.1116. Epub 2010 Dec 17.
62	A New ISL1 Loss-of-Function Mutation Predisposes to Congenital Double Outlet Right Ventricle.Int Heart J. 2019 Sep 27;60(5):1113-1122. doi: 10.1536/ihj.18-685. Epub 2019 Sep 4.
63	Novel mutations in the transcriptional activator domain of the human TBX20 in patients with atrial septal defect.Biomed Res Int. 2015;2015:718786. doi: 10.1155/2015/718786. Epub 2015 Mar 5.