2m9w

Structural highlights

Disease

[GATA4_HUMAN] Partial atrioventricular canal;Tetralogy of Fallot;Familial atrial fibrillation;8p23.1 microdeletion syndrome;46,XY partial gonadal dysgenesis;Complete atrioventricular canal;Atrial septal defect, ostium secundum type;Ventricular septal defect. Atrial septal defect 2 (ASD2) [MIM:607941]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Patients show other heart abnormalities including ventricular and atrioventricular septal defects, pulmonary valve thickening or insufficiency of the cardiac valves. The disease is not associated with defects in the cardiac conduction system or non-cardiac abnormalities. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[1] [2] [3] [4] [5] [6]} Ventricular septal defect 1 (VSD1) [MIM:614429]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[7] [8] [9] [10] [11]} Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[12] [13]} Atrioventricular septal defect 4 (AVSD4) [MIM:614430]: A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. Note=The disease is caused by mutations affecting the gene represented in this entry.^[14]

Function

[GATA4_HUMAN] Transcriptional activator. Binds to the consensus sequence 5'-AGATAG-3'. Acts as a transcriptional activator of ANF in cooperation with NKX2-5 (By similarity). Promotes cardiac myocyte enlargement.^[15]

References

1. ↑ Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 2003 Jul 24;424(6947):443-7. Epub 2003 Jul 6. PMID:12845333 doi:10.1038/nature01827
2. ↑ Hirayama-Yamada K, Kamisago M, Akimoto K, Aotsuka H, Nakamura Y, Tomita H, Furutani M, Imamura S, Takao A, Nakazawa M, Matsuoka R. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Am J Med Genet A. 2005 May 15;135(1):47-52. PMID:15810002 doi:10.1002/ajmg.a.30684
3. ↑ Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet. 2007 Dec;44(12):779-83. PMID:18055909 doi:10.1136/jmg.2007.052183
4. ↑ Rajagopal SK, Ma Q, Obler D, Shen J, Manichaikul A, Tomita-Mitchell A, Boardman K, Briggs C, Garg V, Srivastava D, Goldmuntz E, Broman KW, Benson DW, Smoot LB, Pu WT. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 2007 Dec;43(6):677-85. Epub 2007 Jun 21. PMID:17643447 doi:10.1016/j.yjmcc.2007.06.004
5. ↑ Chen Y, Mao J, Sun Y, Zhang Q, Cheng HB, Yan WH, Choy KW, Li H. A novel mutation of GATA4 in a familial atrial septal defect. Clin Chim Acta. 2010 Nov 11;411(21-22):1741-5. doi: 10.1016/j.cca.2010.07.021., Epub 2010 Jul 24. PMID:20659440 doi:10.1016/j.cca.2010.07.021
6. ↑ Chen Y, Han ZQ, Yan WD, Tang CZ, Xie JY, Chen H, Hu DY. A novel mutation in GATA4 gene associated with dominant inherited familial atrial septal defect. J Thorac Cardiovasc Surg. 2010 Sep;140(3):684-7. doi:, 10.1016/j.jtcvs.2010.01.013. Epub 2010 Mar 26. PMID:20347099 doi:10.1016/j.jtcvs.2010.01.013
7. ↑ Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet. 2007 Dec;44(12):779-83. PMID:18055909 doi:10.1136/jmg.2007.052183
8. ↑ Zhang W, Li X, Shen A, Jiao W, Guan X, Li Z. GATA4 mutations in 486 Chinese patients with congenital heart disease. Eur J Med Genet. 2008 Nov-Dec;51(6):527-35. doi: 10.1016/j.ejmg.2008.06.005. Epub, 2008 Jul 11. PMID:18672102 doi:10.1016/j.ejmg.2008.06.005
9. ↑ Peng T, Wang L, Zhou SF, Li X. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica. 2010 Dec;138(11-12):1231-40. doi: 10.1007/s10709-010-9522-4. Epub 2010 , Nov 26. PMID:21110066 doi:10.1007/s10709-010-9522-4
10. ↑ Wang J, Fang M, Liu XY, Xin YF, Liu ZM, Chen XZ, Wang XZ, Fang WY, Liu X, Yang YQ. A novel GATA4 mutation responsible for congenital ventricular septal defects. Int J Mol Med. 2011 Oct;28(4):557-64. doi: 10.3892/ijmm.2011.715. Epub 2011 Jun, 1. PMID:21637914 doi:10.3892/ijmm.2011.715
11. ↑ Yang YQ, Li L, Wang J, Liu XY, Chen XZ, Zhang W, Wang XZ, Jiang JQ, Liu X, Fang WY. A novel GATA4 loss-of-function mutation associated with congenital ventricular septal defect. Pediatr Cardiol. 2012 Apr;33(4):539-46. doi: 10.1007/s00246-011-0146-y. Epub 2011, Nov 20. PMID:22101736 doi:10.1007/s00246-011-0146-y
12. ↑ Zhang W, Li X, Shen A, Jiao W, Guan X, Li Z. GATA4 mutations in 486 Chinese patients with congenital heart disease. Eur J Med Genet. 2008 Nov-Dec;51(6):527-35. doi: 10.1016/j.ejmg.2008.06.005. Epub, 2008 Jul 11. PMID:18672102 doi:10.1016/j.ejmg.2008.06.005
13. ↑ Peng T, Wang L, Zhou SF, Li X. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica. 2010 Dec;138(11-12):1231-40. doi: 10.1007/s10709-010-9522-4. Epub 2010 , Nov 26. PMID:21110066 doi:10.1007/s10709-010-9522-4
14. ↑ Rajagopal SK, Ma Q, Obler D, Shen J, Manichaikul A, Tomita-Mitchell A, Boardman K, Briggs C, Garg V, Srivastava D, Goldmuntz E, Broman KW, Benson DW, Smoot LB, Pu WT. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 2007 Dec;43(6):677-85. Epub 2007 Jun 21. PMID:17643447 doi:10.1016/j.yjmcc.2007.06.004
15. ↑ Sunagawa Y, Morimoto T, Takaya T, Kaichi S, Wada H, Kawamura T, Fujita M, Shimatsu A, Kita T, Hasegawa K. Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes. J Biol Chem. 2010 Mar 26;285(13):9556-68. doi: 10.1074/jbc.M109.070458. Epub 2010, Jan 17. PMID:20081228 doi:10.1074/jbc.M109.070458