From Compendium of Cancer Genome Aberrations
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Primary Author(s)*

Kay Weng Choy, MBBS, Monash Medical Centre


GATA Binding Protein 2, IMD21, NFE1B, DCML (dendritic cell, monocyte, and lymphoid deficiency), MONOMAC (Monocytopenia and Mycobacterium avium complex infections)

Genomic Location

Cytoband: 3q21.3

Genomic Coordinates:

chr3:128,479,422-128,493,187 (GRCh38/hg38)

chr3:128,198,265-128,212,030 (GRCh37/hg19)

Cancer Category/Type

--- Myeloid Neoplasms with Germline GATA2 Mutation

Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)

Chronic myeloid leukemia (CML)

Non-small cell lung cancer (NSCLC)

Gene Overview

Guanine-adenine-thymine-adenine 2 (GATA2) is one of six GATA binding-factors that regulate gene expression by binding to the DNA motif GATA motifs in the human genome and other transcription factors via two zinc finger domains (ZF1 and ZF2) [1]. During embryogenesis, GATA2 plays an important role in the endothelial to hematopoietic transition that produces the first adult hematopoietic stem cells (HSCs) [2]. In adult hematopoiesis, it is an important transcriptional regulator of hematopoiesis required for HSCs survival and self-renewal [3,4,5]. GATA2 interacts with a complex network of transcription factors that determine early lineage commitment, including SPI1 (PU.1), FLI1, TAL1 (SCL), LMO2 and RUNX1 [3,4,5]. During hematopoietic differentiation, GATA2 is presumed to play a key role in downstream fate decisions together with CEBPA, GATA1 and SPI1, and is essential for monocytic, granulocytic, and lymphoid differentiation (figure 1) [1]. Antagonism between pairs of transcription factors is a key feature of fate decisions, an example being GATA2 and SPI1 (PU.1) in influencing the spectrum of early commitment [1].

Three GATA2 transcripts have been described [1]. Two transcripts (NM_001145661.1 and NM_032638.4) encode the same isoform 1 (480 residues) [1]. A third transcript (NM_001145662.1) encodes a shorter isoform 2 which is truncated by 14 residues at the second zinc finger, as a result of alternative splicing of the last exon [1]. Expression of the distal first exon (IS) is restricted to hematopoiesis and is involved in specification of definitive HSCs during embryogenesis [1]. GATA2 mutated disorders include MonoMac syndrome (Monocytopenia and Mycobacterium avium complex infections), congenital neutropenia, congenital lymphedema (Emberger’s syndrome), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia), sensorineural defects, viral warts, and a spectrum of aggressive infections seen across all age groups [2].


GATA2 overexpression has been reported in up to half of non-familial AML and correlates with poor prognosis with shorter overall and event-free survival when treated with standard chemotherapy [6,7]. Bone marrow biopsies are frequently hypocellular in contrast to the common MDS marrow picture, with abundant atypical megakaryocytes in >90% of patients [8]. AML with inv(3)(q21;3q26.2)/t(3;3)(q21.3;q26.2) accounts for 1-2% of all AML [9]. It is an aggressive disease with short survival [9]. It is associated with aberrant expression of the stem-cell regulator EVI1 [9]. Both 3q rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, identified as the cause of sporadic familial AML/MDS (and MonoMac/Emberger syndromes) [9].


GATA2 mutation Leu359Val (NM_001145661.1:c.1075T>G) gain-of-function has been found in approximately 10% of patients with accelerated or blast phase CML but not chronic lymphocytic leukemia (CLL) or acute lymphoblastic leukemia (ALL) [10,11]. This is thought to be mediated through PU.1 inhibition [2]. While GATA2 overexpression has been associated with AML, and Leu359Val gain-of-function mutation with CML, loss-of-function mutations of GATA2 such as Thr354Met (NM_001145661.1:c.1061C>T) have been linked to MDS [2]. Leu359 and Thr354 are located in the same region on the second zinc finger of GATA2, highlighting the influence of GATA2 in myeloid precursors [2].

Non-small cell lung cancer (NSCLC)

The GATA2 transcriptional network is a requisite for RAS oncogene-driven NSCLC [12]. Loss of GATA2 reduced the viability of NSCLC cells with RAS-pathway mutations, whereas wild-type cells were unaffected [12]. In a Kras-driven NSCLC mouse model, Gata2 loss dramatically reduced tumor development [12]. Furthermore, Gata2 deletion in established Kras-mutant tumors has been found to induce significant regression [12].

Common Alteration Types

GATA2 mutations include amino acid substitutions, insertion and deletions, and frameshifts scattered throughout the gene but predominantly found in the region encoding the two zinc finger domains [1]. Approximately 100 GATA2 mutations have been described, either as germline genetic defects or somatic mutations in association with other drivers, such as biallelic CEBPA mutation in AML [1].

• About one-third of all germline mutations are inherited and the rest occur de novo; these include a small number of whole gene deletions and 29 frameshift or nonsense mutations, distributed from the initiation site to the end of the second zinc finger

• A further 11 in-frame insertions or deletions and 54 single nucleotide variants causing amino acid substitution are predominantly found in exons 3, 4 and 5, encoding the two zinc finger domains

• Splice site mutations are also found between coding exons 3 and 4

• Two discrete mutations of the intron 5 enhancer, predicted to affect transcription factor binding, have also been reported

• Overall, approximately two-thirds of all cases described have mutations in the zinc finger domains

• No mutations have been observed in the 5’ or 3’ untranslated regions (UTRs) or in the distal section of the last exon, beyond the region encoding the second zinc finger

• Many single amino acid substitutions are predicted to significantly impair DNA binding of the zinc fingers potentially making them functionally inactive. It is also possible that these variants have residual function or can even act in a dominant negative fashion

• Although more than half the variants described are single amino acid substitutions that may lead to the translation of mutated protein with altered function, it is proposed that the functional effects of heterozygous mutations are primarily due to haploinsufficiency

According to the Catalogue of Somatic Mutations in Cancer (COSMIC), c.490G>A (NM_032638.4) (p.Ala164Thr) and c.15C>G (NM_032638.4) (p.Pro5Pro) have been observed in 49 and 96 cases, respectively, predominantly in the setting of acute myeloid leukemia (, Accessed 1st August 2018)

Internal Pages

Acute Myeloid Leukemia (AML) with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM

Myeloid Neoplasms with Germline GATA2 Mutation

External Links

GATA2 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

GATA2 by COSMIC - sequence information, expression, catalogue of mutations

GATA2 by CIViC - general knowledge and evidence-based variant specific information

GATA2 by St. Jude ProteinPaint mutational landscape and matched expression data.

GATA2 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

GATA2 by Cancer Index - gene, pathway, publication information matched to cancer type

GATA2 by OncoKB - mutational landscape, mutation effect, variant classification

GATA2 by NCBI Gene - brief gene overview

GATA2 by My Cancer Genome - brief gene overview

GATA2 by UniProt - protein and molecular structure and function

GATA2 by Pfam - gene and protein structure and function information

GATA2 by GeneCards - general gene information and summaries

GATA2 by OMIM - compendium of human genes and genetic phenotypes

GATA2 by LOVD(3) - Leiden Open Variation Database

GATA2 by TICdb - database of Translocation breakpoints In Cancer


1. Collin M, et al., (2015). Haematopoietic and immune defects associated with GATA2 mutation. Br J Haematol 169(2):173-187. PMID 25707267

2. Tsai FY, et al., (1994). An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371(6494):221-226. PMID 8078582

3. Doré LC, et al., (2012). Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis. Blood 119(16):3724-3733. PMID 22383799

4. May G, et al., (2013). Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors. Cell Stem Cell 13(6):754-768. PMID 24120743

5. Beck D, et al., (2013). Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes. Blood 122(14);e12-e22. PMID 23974199

6. Vicente C, et al., (2012). Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities. Leukemia 26(3):550-554. PMID 21904383

7. Ayala RM, et al., (2009). Clinical significance of Gata-1, Gata-2, EKLF, and c-MPL expression in acute myeloid leukemia. Am J Hematol 84(20:79-86. PMID 19097174

8. Spinner MA, et al., (2014). GATA2 deficiency: a protein disorder of hematopoiesis, lymphatics, and immunity. Blood 123(6):809-821. PMID 24227816

9. Gröschel S, et al., (2014). A single oncogenic enhancer rearrangement cause concomitant EVI1 and GATA2 reregulation in leukemia. Cell 157(20):369-381. PMID 24703711

10. Zhang SJ, et al., (2008). Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci U S A 105(6):2076-2081. PMID 18250304

11. Zhang SJ, et al., (2009). GATA-2 L359V mutation is exclusively associated with CML progression but no other haematological malignancies and GATA-2 P250A is a novel single nucleotide polymorphism. PMID 19304323

12. Kumar MS, et al., (2012). The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer. PMID 22541434


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