Gene Symbol: GATA-4
Description: GATA binding protein 4
Alias: ASD2, TACHD, TOF, VSD1, transcription factor GATA-4, GATA-binding factor 4
Species: human
Products:     GATA-4

Top Publications

  1. Hellebrekers D, Lentjes M, van den Bosch S, Melotte V, Wouters K, Daenen K, et al. GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. Clin Cancer Res. 2009;15:3990-7 pubmed publisher
    ..GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection. ..
  2. Chen M, Pang Y, Guo Y, Pan J, Liu B, Shen J, et al. GATA4 mutations in Chinese patients with congenital cardiac septal defects. Pediatr Cardiol. 2010;31:85-9 pubmed publisher
    ..Our finding suggests that the mutations in the transcription factor GATA4 might be related to congenital cardiac septal defects in Han ancestry patients. ..
  3. Tomita Mitchell A, Maslen C, Morris C, Garg V, Goldmuntz E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet. 2007;44:779-83 pubmed
    ..These data suggest that non-synonymous GATA4 sequence variants are found in a small percentage of patients with septal defects and are very uncommonly found in patients with conotruncal defects. ..
  4. Cai K, Caslini C, Capo Chichi C, Slater C, Smith E, Wu H, et al. Loss of GATA4 and GATA6 expression specifies ovarian cancer histological subtypes and precedes neoplastic transformation of ovarian surface epithelia. PLoS ONE. 2009;4:e6454 pubmed publisher
    ..The readily loss of GATA4 expression through changes in chromatin conformation suggests a potential non-phenotypic initiating event, leading to subsequent loss of GATA6, morphological transformation, and ultimate tumorigenesis. ..
  5. Posch M, Perrot A, Schmitt K, Mittelhaus S, Esenwein E, Stiller B, et al. Mutations in GATA4, NKX2.5, CRELD1, and BMP4 are infrequently found in patients with congenital cardiac septal defects. Am J Med Genet A. 2008;146A:251-3 pubmed
  6. Crispino J, Lodish M, Thurberg B, Litovsky S, Collins T, Molkentin J, et al. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Genes Dev. 2001;15:839-44 pubmed
    ..We also infer that GATA-4 function is dependent on interaction with FOG-2 and, very likely, an additional FOG protein for distinct aspects of heart formation. ..
  7. Joziasse I, van der Smagt J, Poot M, Hochstenbach R, Nelen M, van Gijn M, et al. A duplication including GATA4 does not co-segregate with congenital heart defects. Am J Med Genet A. 2009;149A:1062-6 pubmed publisher
  8. Caslini C, Capo chichi C, Roland I, Nicolas E, Yeung A, Xu X. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene. 2006;25:5446-61 pubmed
  9. Akiyama Y, Watkins N, Suzuki H, Jair K, van Engeland M, Esteller M, et al. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol. 2003;23:8429-39 pubmed
    ..Selection for silencing of both upstream transcription factors and their target genes in GI cancers could indicate that epigenetic silencing of the involved genes provides a summated contribution to tumor progression. ..

More Information


  1. 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;51:527-35 pubmed publisher
    ..Our findings are useful in understanding the prevalence of GATA4 mutations and the correlation between the GATA4 genotype and the CHD phenotype in Chinese patients. ..
  2. Salazar M, Consoli F, Villegas V, Caicedo V, Maddaloni V, Daniele P, et al. Search of somatic GATA4 and NKX2.5 gene mutations in sporadic septal heart defects. Eur J Med Genet. 2011;54:306-9 pubmed publisher
  3. Anttonen M, Pihlajoki M, Andersson N, Georges A, L hôte D, Vattulainen S, et al. FOXL2, GATA4, and SMAD3 co-operatively modulate gene expression, cell viability and apoptosis in ovarian granulosa cell tumor cells. PLoS ONE. 2014;9:e85545 pubmed publisher
    ..Thus, the effects of GATA4 and SMAD3 on both cell viability and apoptosis are distinct from those of wild type FOXL2; a perturbation of this balance due to the oncogenic FOXL2 mutation is likely to contribute to GCT pathogenesis. ..
  4. Wen X, Akiyama Y, Pan K, Liu Z, Lu Z, Zhou J, et al. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World J Gastroenterol. 2010;16:1201-8 pubmed
    ..023 and 0.027, two-sides). Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection. ..
  5. Durocher D, Charron F, Warren R, Schwartz R, Nemer M. The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors. EMBO J. 1997;16:5687-96 pubmed
    ..Given the co-expression of GATA proteins and NK2 class members in other tissues, the GATA/Nkx partnership may represent a paradigm for transcription factor interaction during organogenesis. ..
  6. Wakana K, Akiyama Y, Aso T, Yuasa Y. Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis. Cancer Lett. 2006;241:281-8 pubmed
    ..These data suggest that GATA-4/-5 may be involved in ovarian carcinogenesis. ..
  7. Schluterman M, Krysiak A, Kathiriya I, Abate N, Chandalia M, Srivastava D, et al. Screening and biochemical analysis of GATA4 sequence variations identified in patients with congenital heart disease. Am J Med Genet A. 2007;143A:817-23 pubmed
  8. Agnihotri S, Wolf A, Munoz D, Smith C, Gajadhar A, Restrepo A, et al. A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas. J Exp Med. 2011;208:689-702 pubmed publisher
    ..Identification and validation of GATA4 as a TSG and its downstream targets in GBM may yield promising novel therapeutic strategies. ..
  9. De Luca A, Sarkozy A, Ferese R, Consoli F, Lepri F, Dentici M, et al. New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle. Clin Genet. 2011;80:184-90 pubmed publisher a large cohort of individuals with CTD, including tetralogy of Fallot with or without pulmonary atresia (TOF, 178 patients), double outlet right ventricle (DORV, 13 patients), and truncus arteriosus (11 patients)...
  10. Agnihotri S, Wolf A, Picard D, Hawkins C, Guha A. GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system. Oncogene. 2009;28:3033-46 pubmed publisher
    ..Collectively, we show that GATA4 is expressed in the embryonic and adult CNS and acts as a negative regulator of astrocyte proliferation and growth. ..
  11. Kyrönlahti A, Rämö M, Tamminen M, Unkila Kallio L, Butzow R, Leminen A, et al. GATA-4 regulates Bcl-2 expression in ovarian granulosa cell tumors. Endocrinology. 2008;149:5635-42 pubmed publisher
    ..Our results reveal a previously unknown relationship between GATA-4 and Bcl-2 in mammalian granulosa cells and GCTs, and suggest that GATA-4 influences granulosa cell fate by transactivating Bcl-2. ..
  12. Tang Z, Xia L, Chang W, Li H, Shen F, Liu J, et al. Two novel missense mutations of GATA4 gene in Chinese patients with sporadic congenital heart defects. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23:134-7 pubmed
    ..The above identified two novel GATA4 mutations associated with CHD in Chinese patients. This suggests that the transcription factor GATA4 may play an important role in cardiogenesis. ..
  13. Brewer A, Alexandrovich A, Mjaatvedt C, Shah A, Patient R, Pizzey J. GATA factors lie upstream of Nkx 2.5 in the transcriptional regulatory cascade that effects cardiogenesis. Stem Cells Dev. 2005;14:425-39 pubmed
  14. Dai Y, Cserjesi P, Markham B, Molkentin J. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J Biol Chem. 2002;277:24390-8 pubmed
  15. Hirayama Yamada K, Kamisago M, Akimoto K, Aotsuka H, Nakamura Y, Tomita H, et al. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Am J Med Genet A. 2005;135:47-52 pubmed
    ..5 for which classification has not been clearly proposed. This pinpoints essential sites of NKX2.5 in the development of the conduction system. ..
  16. Liang Q, Wiese R, Bueno O, Dai Y, Markham B, Molkentin J. The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes. Mol Cell Biol. 2001;21:7460-9 pubmed
  17. Nemer G, Fadlalah F, Usta J, Nemer M, Dbaibo G, Obeid M, et al. A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot. Hum Mutat. 2006;27:293-4 pubmed
    ..This mutation was found in two out of 26 patients with Tetralogy of Fallot (TOF), and in none of the 94 patients with different phenotypes included in the study, nor in 223 healthy individuals...
  18. Sherin C, Francesca F, Karl P, Brendan T, Ron H, Lyn G. Investigation between the S377G3 GATA-4 polymorphism and migraine. Open Neurol J. 2008;2:35-8 pubmed publisher
    ..84, P = 0.66). Thus it appears that the GATA-4 (S377G) mutation does not play a significant role in common migraine susceptibility. ..
  19. Vaitkiene P, Skiriute D, Skauminas K, Tamasauskas A. GATA4 and DcR1 methylation in glioblastomas. Diagn Pathol. 2013;8:7 pubmed publisher
    ..The virtual slide(s) for this article can be found here: ..
  20. Guo M, House M, Akiyama Y, Qi Y, Capagna D, Harmon J, et al. Hypermethylation of the GATA gene family in esophageal cancer. Int J Cancer. 2006;119:2078-83 pubmed
    ..Our studies demonstrate frequent silencing of GATA-4 and GATA-5, but not GATA-6, in human esophageal neoplasia associated with gene promoter hypermethylation. ..
  21. Gao X, Sedgwick T, Shi Y, Evans T. Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation. Mol Cell Biol. 1998;18:2901-11 pubmed
    ..Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP. ..
  22. Peng T, Wang L, Zhou S, Li X. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica. 2010;138:1231-40 pubmed publisher
    ..This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted. ..
  23. Escaffit F, Boudreau F, Beaulieu J. Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. J Cell Physiol. 2005;203:15-26 pubmed
    ..These observations suggest that optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization. ..
  24. Liu X, Wang J, Zheng J, Bai K, Liu Z, Wang X, et al. Involvement of a novel GATA4 mutation in atrial septal defects. Int J Mol Med. 2011;28:17-23 pubmed publisher
    ..The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies. ..
  25. Guo M, Akiyama Y, House M, Hooker C, Heath E, Gabrielson E, et al. Hypermethylation of the GATA genes in lung cancer. Clin Cancer Res. 2004;10:7917-24 pubmed
    ..001). These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly. ..
  26. Zhang W, Li X, Ma Z, Zhang J, Zhou S, Li T, et al. GATA4 and NKX2.5 gene analysis in Chinese Uygur patients with congenital heart disease. Chin Med J (Engl). 2009;122:416-9 pubmed
    ..There were no reported NKX2.5 mutations in the patients. Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population. ..
  27. Nemer G, Nemer M. Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol. 2003;254:131-48 pubmed
    ..They also raise the possibility that part of the early defects in GATA-4 and/or GATA-6 null embryos may be due to impaired BMP-4 signaling. ..
  28. Chen Y, Mao J, Sun Y, Zhang Q, Cheng H, Yan W, et al. A novel mutation of GATA4 in a familial atrial septal defect. Clin Chim Acta. 2010;411:1741-5 pubmed publisher
    ..Both mutations were not identified among healthy controls. T280M mutation of GATA4 is suggested to be associated with ASD in this Chinese family. ..
  29. Reamon Buettner S, Borlak J. GATA4 zinc finger mutations as a molecular rationale for septation defects of the human heart. J Med Genet. 2005;42:e32 pubmed
  30. Wang J, Fang M, Liu X, Xin Y, Liu Z, Chen X, et al. A novel GATA4 mutation responsible for congenital ventricular septal defects. Int J Mol Med. 2011;28:557-64 pubmed publisher
    ..The results of the present study imply the potential implications in the genetic diagnosis and gene-specific therapy of this common malformation in infancy. ..
  31. Skerjanc I, Petropoulos H, Ridgeway A, Wilton S. Myocyte enhancer factor 2C and Nkx2-5 up-regulate each other's expression and initiate cardiomyogenesis in P19 cells. J Biol Chem. 1998;273:34904-10 pubmed
    ..These findings indicate the presence of a positive regulatory network between Nkx2-5 and MEF2C and show that both factors can direct early stages of cell differentiation into a cardiomyogenic pathway. ..
  32. Svensson E, Tufts R, Polk C, Leiden J. Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes. Proc Natl Acad Sci U S A. 1999;96:956-61 pubmed
  33. Riazi A, Lee H, Hsu C, Van Arsdell G. CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro. J Biol Chem. 2005;280:10716-20 pubmed
    ..This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor. ..
  34. Wang J, Lu Y, Chen H, Yin M, Yu T, Fu Q. Investigation of somatic NKX2-5, GATA4 and HAND1 mutations in patients with tetralogy of Fallot. Pathology. 2011;43:322-6 pubmed publisher
    Tetralogy of Fallot (TOF) is the most common type of congenital heart disease (CHD). Several genes essential for heart development have been identified...
  35. Reamon Buettner S, Cho S, Borlak J. Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD). BMC Med Genet. 2007;8:38 pubmed
    ..In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II. Our results suggest that somatic GATA4 mutations in the 3'-UTR may provide an additional molecular rationale for CHD. ..
  36. Rajagopal S, Ma Q, Obler D, Shen J, Manichaikul A, Tomita Mitchell A, et al. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 2007;43:677-85 pubmed
    ..Additional studies will be required to determine the degree to which GATA4 mutation contributes to human CHD characterized by ECD or RV hypoplasia. ..
  37. Garg V, Kathiriya I, Barnes R, Schluterman M, King I, Butler C, et al. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 2003;424:443-7 pubmed
    ..These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5. ..
  38. Ito H, Yoshida K, Murakami M, Hagiwara K, Sasaki N, Kobayashi M, et al. Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines. Biochim Biophys Acta. 2011;1811:119-28 pubmed publisher
    ..Thus, high SPL transcription of H1155 cells was regulated by Sp1 and GATA-4/Sp1 complex formation, both of which bind to Sp1 sites of the 5'-SPL promoter. ..
  39. Wang E, Sun S, Qiao B, Duan W, Huang G, An Y, et al. Identification of functional mutations in GATA4 in patients with congenital heart disease. PLoS ONE. 2013;8:e62138 pubmed publisher
    ..Together with the newly reported mutations, approximately 110 non-synonymous mutations have currently been identified in GATA4. Our future analysis will explore why the evolutionarily conserved GATA4 appears to be hypermutable. ..
  40. Kyrönlahti A, Kauppinen M, Lind E, Unkila Kallio L, Butzow R, Klefstrom J, et al. GATA4 protects granulosa cell tumors from TRAIL-induced apoptosis. Endocr Relat Cancer. 2010;17:709-17 pubmed publisher
    ..Our results demonstrate that the TRAIL pathway is functional in GCT cells, and suggest that transcription factor GATA4 may function as a survival factor in this ovarian malignancy. ..
  41. Molkentin J, Kalvakolanu D, Markham B. Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene. Mol Cell Biol. 1994;14:4947-57 pubmed
    ..This indicates a mechanism whereby triiodothyronine and retinoic acid can exert coordinate control of the cardiac phenotype through a trans-acting regulatory factor. ..
  42. Arceci R, King A, Simon M, Orkin S, Wilson D. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993;13:2235-46 pubmed
    ..On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads. ..
  43. Flück C, Miller W. GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1. Mol Endocrinol. 2004;18:1144-57 pubmed
    ..Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells. ..
  44. Zhang L, Tumer Z, Jacobsen J, Andersen P, Tommerup N, Larsen L. Screening of 99 Danish patients with congenital heart disease for GATA4 mutations. Genet Test. 2006;10:277-80 pubmed
    ..Thus, the diagnostic importance of GATA4 mutations may be confined to familial cases or specific subgroups of CHD phenotypes. ..
  45. Morin S, Charron F, Robitaille L, Nemer M. GATA-dependent recruitment of MEF2 proteins to target promoters. EMBO J. 2000;19:2046-55 pubmed
    ..The results unravel a novel pathway for transcriptional regulation by MEF2 and provide a molecular paradigm for elucidating the mechanisms of action of MEF2 in muscle and non-muscle cells. ..
  46. Butler T, Esposito G, Blue G, Cole A, Costa M, Waddell L, et al. GATA4 mutations in 357 unrelated patients with congenital heart malformation. Genet Test Mol Biomarkers. 2010;14:797-802 pubmed publisher
    ..Our data expand the spectrum of mutations associated with cardiac septal defects but do not support GATA4 mutations as a common cause of CHD. ..
  47. Okubo A, Miyoshi O, Baba K, Takagi M, Tsukamoto K, Kinoshita A, et al. A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family. J Med Genet. 2004;41:e97 pubmed
  48. Hua G, Zhu B, Rosa F, Deblon N, Adélaïde J, Kahn Perlès B, et al. A negative feedback regulatory loop associates the tyrosine kinase receptor ERBB2 and the transcription factor GATA4 in breast cancer cells. Mol Cancer Res. 2009;7:402-14 pubmed publisher
    ..We propose that the negative feedback loop linking ERBB2 and GATA4 plays a role in the transcriptional dysregulation of ERBB2 gene expression in breast cancer. ..
  49. Belaguli N, Zhang M, Rigi M, Aftab M, Berger D. Cooperation between GATA4 and TGF-beta signaling regulates intestinal epithelial gene expression. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1520-33 pubmed
    ..Our results suggest that the TGF-beta signaling regulates gut epithelial gene expression by targeting GATA4. ..
  50. Anttonen M, Unkila Kallio L, Leminen A, Butzow R, Heikinheimo M. High GATA-4 expression associates with aggressive behavior, whereas low anti-Müllerian hormone expression associates with growth potential of ovarian granulosa cell tumors. J Clin Endocrinol Metab. 2005;90:6529-35 pubmed
    ..0-43.3; P = 0.0048). The more aggressive GCTs retain a high GATA-4 expression, whereas the larger tumors lose the proliferation-suppressing AMH expression. The high GATA-4 expression in GCTs may serve as a marker of poor prognosis. ..
  51. Esposito G, Butler T, Blue G, Cole A, Sholler G, Kirk E, et al. Somatic mutations in NKX2–5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart. Am J Med Genet A. 2011;155A:2416-21 pubmed
    ..We used samples of right ventricular myocardium from patients undergoing surgical repair of tetralogy of Fallot (TOF) and hypoplastic left heart (HLH) to examine the incidence of somatic mutation in cardiac tissue...
  52. White R, Dowler L, Pasztor L, Gatson L, Adkison L, Angeloni S, et al. Assignment of the transcription factor GATA4 gene to human chromosome 8 and mouse chromosome 14: Gata4 is a candidate gene for Ds (disorganization). Genomics. 1995;27:20-6 pubmed
    ..We speculate that Ds is caused by a mutation in the Gata4 gene, ectopic expression of GATA-4, or a mutation in another lineage determination gene closely linked to Gata4. ..
  53. Bouchard M, Taniguchi H, Viger R. The effect of human GATA4 gene mutations on the activity of target gonadal promoters. J Mol Endocrinol. 2009;42:149-60 pubmed publisher
    ..Thus, unlike the heart, where the GATA4 mutations have deleterious effects, our data suggest that they would have a lesser impact on gonadal gene transcription and function. ..