GATA4

This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants.

GATA binding protein 4

Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development and function (PubMed:24000169, PubMed:27984724).

In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it downregulates endocardial and endothelial gene expression (PubMed:27984724).

Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity).

Acts as a transcriptional activator of ANF in cooperation with NKX2-5 (By similarity).

Promotes cardiac myocyte enlargement (PubMed:20081228).

Required during testicular development (PubMed:21220346).

May play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate degrading enzyme, sphingosine-1-phosphate lyase (PubMed:15734735).

Aortic valve morphogenesis Source: BHF-UCL
Atrial septum morphogenesis Source: BHF-UCL
Atrial septum primum morphogenesis Source: BHF-UCL
Atrial septum secundum morphogenesis Source: BHF-UCL
Atrioventricular canal development Source: BHF-UCL
Atrioventricular node development Source: BHF-UCL
Atrioventricular valve formation Source: BHF-UCL
Cardiac muscle tissue regeneration Source: BHF-UCL
Cardiac right ventricle morphogenesis Source: BHF-UCL
Cardiac ventricle morphogenesis Source: BHF-UCL
Cell-cell signaling Source: BHF-UCL
Cell fate commitment Source: GO_Central
Cell growth involved in cardiac muscle cell development Source: Ensembl
Cellular response to glucose stimulus Source: Ensembl
Embryonic foregut morphogenesis Source: BHF-UCL
Embryonic heart tube anterior/posterior pattern specification Source: BHF-UCL
Endocardial cushion development Source: BHF-UCL
Endoderm development Source: BHF-UCL
Heart looping Source: BHF-UCL
Intestinal epithelial cell differentiation Source: MGI
Male gonad development Source: UniProtKB
Negative regulation of apoptotic signaling pathway Source: BHF-UCL
Negative regulation of autophagy Source: Ensembl
Negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
Negative regulation of oxidative stress-induced cell death Source: BHF-UCL
Positive regulation of angiogenesis Source: BHF-UCL
Positive regulation of BMP signaling pathway Source: Ensembl
Positive regulation of cardioblast differentiation Source: BHF-UCL
Positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of vascular endothelial growth factor production Source: BHF-UCL
Regulation of cardiac muscle cell contraction Source: Ensembl
Regulation of protein kinase B signaling Source: BHF-UCL
Regulation of transcription, DNA-templated Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to drug Source: BHF-UCL
Response to mechanical stimulus Source: Ensembl
Response to vitamin A Source: Ensembl
Transdifferentiation Source: Ensembl
Ventricular septum development Source: BHF-UCL
Wound healing Source: BHF-UCL

Nucleus

Atrial septal defect 2 (ASD2):
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.
Ventricular septal defect 1 (VSD1):
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.
Tetralogy of Fallot (TOF):
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.
Atrioventricular septal defect 4 (AVSD4):
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.
Testicular anomalies with or without congenital heart disease (TACHD):
A 46,XY disorder of sex development with variable clinical presentation and defects in testicular differentiation and function. Clinical features include ambiguous genitalia, fused labioscrotal folds, hypospadias, microphallus, and bilateral inguinal hernia containing gonads.
GATA4 mutations can predispose to dilated cardiomyopathy (CMD), a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.

Methylation at Lys-300 attenuates transcriptional activity.