GATA2 (GATA binding protein 2)

2015-11-01   Ritsuko Shimizu , Masayuki Yamamoto 

Tohoku University Graduate School of Medicine, Sendai, Japan


3q21.3 128,479,427-128,493,185 reverse strand


Review on GATA2, with data on DNA, on the protein encoded, and where the gene is implicated.



Genomic DNA 13,759bp, 6 exons ((two untranslated first exons that utilized differentially and five translated exons).


The distal (IS) exon specifically utilized in hematopoietic and neural cells, while the proximal (IG) exon is utilized ubiquitously, producing 3383-bp and 3484-bp transcripts, respectively. These two variant transcripts encode the same protein. Trancription is oriented from telomere to centromere.



Contains 2 zinc finger domains, ZF1 (aa 294 to 344) and ZF2 (aa 349 to 398).


Strictly regulated and tissue specific. Gene activity depends on several trans regulators and cis-acting regulatory elements scattered in a wide range around the gene. 3.1-kbp upstream of IS exon recapitulates endogenous Gata2 gene expression in yolk sacs and paraaortic splanchnopleura hematopoietic cells in mice. An enhancer in 77-kbp upstream of GATA2 gene and GATA-box-E-box composite element in the fourth intron are important in adult hematopoiesis and implicated in the leukemogenesis in humans (see below). In non-hematopoietic tissues, the element in the fourth intron works as an endothelial specific enhancer, whereas enhancer(s) located between +75- and +113-kbp to the translational initiation site are responsible to the Gata2 expression in caudal periureteric mesenchyme/ urogenital sinus and rostral metanephric mesenchyme in mice, respectively. It has been considered that currently not-identified enhancer(s) for urogenital organs development are located more distal region of Gata2 gene..




Binds to the consensus sequence 5-(A/T)GATA(A/G)-3. Transcriptional activator which is expressed very early in hematopoiesis and plays a role in development and regulation of every early pluripotent hematopoietic precursor, but also of eosinophils, basophils and mast cells. Early stages of erythroid differentiation depends of GATA2, but during maturation GATA2 expression decreases progressively at the benefit of GATA1. GATA2 suppresses differentiation of bone marrow mesenchyme stem cells to adipocytes and sustains the hematopoietic stem cell environment. GATA2 also plays roles in development of neural system, urogenital organs and vascular system.


Member of the GATA family which contains 6 known members; only GATA1, GATA2 and GATA3 are involved in hematopoiesi



Loss-of-function mutations and dominant-negative mutations have been found as a cause of Familial myelodysplastic syndrome (MDS), DCML deficiency and Emberger syndrome, which are in a group of complex syndromes predisposing to leukemia with overlapping clinical features. Mutation in GATA-box-E-box composite element in the fourth intron, which leads to reduction of GATA2 gene expression, has been found in a pedigree of MonoMAC syndrome family.


Chromosomal rearrangements involving the 77-kbp upstream region of GATA2 gene on 3q21 and MECOM (EVI1) gene on 3q26 are associated with MDS and acute myeloid leukemia (AML). This type of hematopoietic malignancies is referred to as 3q21q26 syndrome. Mutations are found as a cause of acute myeloid transformation of chronic myeloid leukemia (CML).

Implicated in

Entity name
DCML deficiency
Immunodeficiency syndrome associated with loss of dendritic cells, monocytes, B and NK cells, leading to the increasing incidence of mycobacterial, fungal and viral infections. This disease occurs sporadically or in an autosomal dominant inheritance with incomplete penetrance. Patients with DCML deficiency have high incidence of developing hematopoietic malignancies. DCML deficiency with mycobacterium avium complex infection has been described as "monoMAC (monocytopenia with Mycobacterium avium complex) syndrome".
Prone to develop MDS and AML.
Entity name
Emberger syndrome
Sporadic or autosomal dominant disease with incomplete penetrance, which has a characteristic feature of primary lymphoedema with myelodysplasia. The lymphedema generally confined to the lower limbs and genitals.
Prone to develop AML.
Entity name
Hematopoietic malignancies, including MDS and AML, caused by a chromosomal aberration between the regions 3q21 and 3q26. The 77-kbp upstream region of GATA2 gene on 3q21 is rearranged proximal to the Evi1 locus on 3q26 by the translocation or inversion. Aberrant expression of EVI1 gene lead by the activity of GATA2 enhancer is appeared to be involved in the pathogenesis and poor prognosis of this disease.
Unfavorable prognosis.
inv(3)(q21q26), t(3;3)(q21;q26).
GATA2 may be involved in APL leukemogenesis by physical interaction with the PML component of PML-RARa fusion or with the variant PLZF-RARa fusion, generated respectively by t(15;17) or t(11;17) translocation.
Entity name
Myelodysplasic syndrome
GATA2 is expressed in MDS, but not in normal controls; the frequency of expression increases with the severity of dysplasia (100% in RAEB/RAEB-T).
Entity name
Myeloid transformation of chronic myelooid leukemia CML
Out of 85 unselected cases of CML blast transformation, 9 showed a GATA2 mutation: 8 with a T-->G substitution at aa359 in ZF2 (L359V) and 1 with a 6 aa deletion (aa 341 to 346) in ZF1. All 9 transformations were myeloid, with a myeloblastic or monoblastic morphology. L359V leads to a gain of function of GATA2 protein.
Entity name
Aplastic anemia (AA)
Hypothetical. In knockout mice, GATA2 haploinsufficiency leads to a decrease of hematopoietic stem cells number and efficiency. In human, GATA2 mRNA expression is largely reduced in patients with AA.
Entity name
Prostate cancer
High expression of GATA2 is associated with aggressiveness, high metastasis ratio and resistance for therapy in prostate cancer through, in part, the activation of androgen-receptor target genes in ligand-independent pathway.
Unfavorable prognosis.
Entity name
Non-small cell lung cancer
GATA2 is required for the survival of Ras-mediated NSCLC by controlling IL-1/NF-κB signaling. Knockdown of GATA2 expression lead to a reduction of tumor burden in mouse model of NSCLC, suggesting that GATA2 is a therapeutic target of Ras mutant cancers.
Entity name
The level of GATA2 expression that might be regulated by EGFR/ERK signaling pathway is correlated with prognosis of glioma patients.
Entity name
The expression level of GATA2 is reverse-correlated with aggressiveness, as GATA2 may negatively regulate proliferation of neuroblastoma cells.
Entity name
Renal cell carcinoma (RCC)
The expression level of GATA2 is reverse-correlated with aggressiveness, possibility of metastasis, and risk of recurrence in clear cell RCC.
Entity name
Hepatocellular carcinoma
The expression level of GATA2 is reverse-correlated with poor prognosis of hepatocellular carcinoma. Knockdown of GATA2 expression enhances the proliferation of a human liver cancer cell line in vitro.
Entity name
Colorectal cancer
High level of GATA2 expression is correlated with aggressive feature, high recurrence rate and poor outcome of colorectal cancer.
Entity name
Breast cancer
Roles of GATA2 in pathogenesis of breast cancer are contraversial. Reports describing that GATA2 level was increased in breast cancer showed that GATA2 might be related to tumor progression by repressing PTEN activity and/or promoting expression of aromatase gene, whereas another report showed that the expression GATA2 gene was silenced by aberrant hyper-methylation of GATA2 promoter region.


Pubmed IDLast YearTitleAuthors
213738862011DNA methylation changes in murine breast adenocarcinomas allow the identification of candidate genes for human breast carcinogenesis.Acosta D et al
196846152009A role for GATA-2 in transition to an aggressive phenotype in prostate cancer through modulation of key androgen-regulated genes.Böhm M et al
182118912008Defining the functional boundaries of the Gata2 locus by rescue with a linked bacterial artificial chromosome transgene.Brandt W et al
121457002002GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome.Fadilah SA et al
113282812001Decreased expression of transcription factor GATA-2 in haematopoietic stem cells in patients with aplastic anaemia.Fujimaki S et al
247037112014A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.Gröschel S et al
169603392006GATA transcription factors and hematological diseases.Harigae H et al
197071952009GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes.Hoene V et al
251502552014GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells.Kamata M et al
173956462007A Gata2 intronic enhancer confers its pan-endothelia-specific regulation.Khandekar M et al
225414342012The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer.Kumar MS et al
244981202014Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma.Li YW et al
75194721994Transcription factor GATA-2 is expressed in erythroid, early myeloid, and CD34+ human leukemia-derived cell lines.Nagai T et al
218921582011Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).Ostergaard P et al
252306942015Decreased mRNA expression of GATA1 and GATA2 is associated with tumor aggressiveness and poor outcome in clear cell renal cell carcinoma.Peters I et al
123516902002Cloning and characterization of a novel endothelial promoter of the human CYP19 (aromatase P450) gene that is up-regulated in breast cancer tissue.Sebastian S et al
109381042000Potentiation of GATA-2 activity through interactions with the promyelocytic leukemia protein (PML) and the t(15;17)-generated PML-retinoic acid receptor alpha oncoprotein.Tsuzuki S et al
220214282012GATA2 negatively regulates PTEN by preventing nuclear translocation of androgen receptor and by androgen-independent suppression of PTEN transcription in breast cancer.Wang Y et al
257077692015GATA2 promotes glioma progression through EGFR/ERK/Elk-1 pathway.Wang Z et al
176540612007GATA-1, -2 and -3 genes expression in bone marrow microenviroment with chronic aplastic anemia.Wu X et al
22497701990Activity and tissue-specific expression of the transcription factor NF-E1 multigene family.Yamamoto M et al
247039062014A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression.Yamazaki H et al
182503042008Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia.Zhang SJ et al

Other Information

Locus ID:

NCBI: 2624
MIM: 137295
HGNC: 4171
Ensembl: ENSG00000179348


dbSNP: 2624
ClinVar: 2624
TCGA: ENSG00000179348


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Factors involved in megakaryocyte development and platelet productionREACTOMER-HSA-983231

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA446108Colorectal NeoplasmsDiseaseMultilinkAnnotationassociated26287967


Pubmed IDYearTitleCitations
216704652011Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome.176
242278162014GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity.175
247037112014A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.173
218921622011Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.171
229420192012A robust model for read count data in exome sequencing experiments and implications for copy number variant calling.152
218921582011Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).149
225414342012The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer.129
217650252011Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency.123
215712182011Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators.116
221478952012Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature.91


Ritsuko Shimizu ; Masayuki Yamamoto

GATA2 (GATA binding protein 2)

Atlas Genet Cytogenet Oncol Haematol. 2015-11-01

Online version:

Historical Card

2009-01-01 GATA2 (GATA binding protein 2) by  Franck Viguié 

Laboratoire de Cytogenetique - Service dHématologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France