GATA2
GATA binding protein 2, the group of GATA zinc finger domain containing
Basic information
Region (hg38): 3:128479427-128493201
Links
Phenotypes
GenCC
Source:
- deafness-lymphedema-leukemia syndrome (Definitive), mode of inheritance: AD
- acute myeloid leukemia (Strong), mode of inheritance: AD
- myelodysplastic syndrome (Strong), mode of inheritance: AD
- deafness-lymphedema-leukemia syndrome (Strong), mode of inheritance: AD
- monocytopenia with susceptibility to infections (Supportive), mode of inheritance: AD
- monocytopenia with susceptibility to infections (Definitive), mode of inheritance: AD
- deafness-lymphedema-leukemia syndrome (Strong), mode of inheritance: AD
- GATA2 deficiency with susceptibility to MDS/AML (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 21; Lymphedema, primary, with myelodsyplasia (Emberger syndrome); Leukemia, acute myeloid, susceptibility to; Myelodysplastic syndrome, susceptibility to | AD | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for myelodysplastic syndrome and related oncologic processes (eg, acute myeloid leukemia) may allow early diagnosis and treatment, which may reduce morbidity and mortality; In Lymphedema, primary, with myelodsyplasia (Emberger syndrome), early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; HSCT has been described | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Hematologic; Oncologic; Pulmonary | 295075; 21765025; 21892162; 21892158; 22147895; 22271902; 23223431; 24227816 |
ClinVar
This is a list of variants' phenotypes submitted to
- GATA2 deficiency with susceptibility to MDS/AML;Deafness-lymphedema-leukemia syndrome (90 variants)
- Deafness-lymphedema-leukemia syndrome;Monocytopenia with susceptibility to infections (25 variants)
- not provided (15 variants)
- Deafness-lymphedema-leukemia syndrome;GATA2 deficiency with susceptibility to MDS/AML (15 variants)
- Monocytopenia with susceptibility to infections;Deafness-lymphedema-leukemia syndrome (11 variants)
- Monocytopenia with susceptibility to infections (8 variants)
- Deafness-lymphedema-leukemia syndrome (6 variants)
- Myelodysplastic syndrome (2 variants)
- Leukemia, acute myeloid, susceptibility to (2 variants)
- Acute myeloid leukemia (2 variants)
- Inborn genetic diseases (1 variants)
- multilineage dysplasia (1 variants)
- GATA2-related disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GATA2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 326 | 332 | ||||
| missense | 35 | 610 | 14 | 669 | ||
| nonsense | 22 | 29 | ||||
| start loss | 1 | |||||
| frameshift | 94 | 13 | 110 | |||
| inframe indel | 25 | 32 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 20 | ||||
| splice region | 2 | 8 | 23 | 33 | ||
| non coding | 45 | 135 | 29 | 211 | ||
| Total | 139 | 69 | 688 | 475 | 33 |
Variants in GATA2
This is a list of pathogenic ClinVar variants found in the GATA2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-128479475-T-C | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128479476-A-G | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128479497-T-C | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-128479601-C-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128479790-T-C | Deafness-lymphedema-leukemia syndrome | Benign (Jan 12, 2018) | ||
| 3-128479846-C-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128479873-T-C | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128479875-C-T | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-128479939-C-T | Deafness-lymphedema-leukemia syndrome | Benign (Jan 13, 2018) | ||
| 3-128480017-C-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 22, 2018) | ||
| 3-128480031-A-C | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-128480135-T-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128480137-A-T | Deafness-lymphedema-leukemia syndrome | Benign (Jan 13, 2018) | ||
| 3-128480304-C-T | Deafness-lymphedema-leukemia syndrome | Benign (Jan 13, 2018) | ||
| 3-128480322-G-A | Deafness-lymphedema-leukemia syndrome | Likely benign (Jan 13, 2018) | ||
| 3-128480438-C-T | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-128480449-G-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-128480473-G-A | Deafness-lymphedema-leukemia syndrome | Benign (Jan 13, 2018) | ||
| 3-128480511-C-T | Deafness-lymphedema-leukemia syndrome | Benign (Jan 12, 2018) | ||
| 3-128480534-AGAG-A | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jun 14, 2016) | ||
| 3-128480537-G-A | Deafness-lymphedema-leukemia syndrome • Monocytopenia with susceptibility to infections;Deafness-lymphedema-leukemia syndrome | Benign (Feb 11, 2022) | ||
| 3-128480562-C-T | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 15, 2018) | ||
| 3-128480592-G-A | Deafness-lymphedema-leukemia syndrome | Benign (Jan 13, 2018) | ||
| 3-128480599-C-T | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-128480601-C-T | Deafness-lymphedema-leukemia syndrome | Uncertain significance (Mar 02, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GATA2 | protein_coding | protein_coding | ENST00000341105 | 5 | 13759 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.979 | 0.0207 | 104874 | 0 | 1 | 104875 | 0.00000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.04 | 195 | 293 | 0.665 | 0.0000155 | 3055 |
| Missense in Polyphen | 111 | 181.17 | 0.61269 | 1905 | ||
| Synonymous | -1.40 | 151 | 131 | 1.16 | 0.00000732 | 1026 |
| Loss of Function | 3.51 | 1 | 16.3 | 0.0615 | 7.96e-7 | 186 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000110 | 0.0000110 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'.;
- Disease
- DISEASE: Lymphedema, primary, with myelodysplasia (LMPM) [MIM:614038]: A chronic disabling condition characterized by swelling of the extremities due to altered lymphatic flow, associated with myelodysplasia. Patients with lymphedema suffer from recurrent local infections, and physical impairment. {ECO:0000269|PubMed:21892158}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:21892162}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- White fat cell differentiation;Adipogenesis;Hematopoietic Stem Cell Differentiation;Preimplantation Embryo;White fat cell differentiation;Transcriptional cascade regulating adipogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Gene expression (Transcription);Generic Transcription Pathway;Factors involved in megakaryocyte development and platelet production;RNA Polymerase II Transcription;Signaling events mediated by HDAC Class II;Hemostasis;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Transcriptional regulation by RUNX1;AP-1 transcription factor network;HIF-1-alpha transcription factor network;Signaling events mediated by HDAC Class I
(Consensus)
Recessive Scores
- pRec
- 0.635
Intolerance Scores
- loftool
- rvis_EVS
- -0.42
- rvis_percentile_EVS
- 25.56
Haploinsufficiency Scores
- pHI
- 0.364
- hipred
- Y
- hipred_score
- 0.837
- ghis
- 0.548
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gata2
- Phenotype
- renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; liver/biliary system phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- gata2a
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- accumulation
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;urogenital system development;cell fate determination;neuron migration;embryonic placenta development;transcription, DNA-templated;phagocytosis;positive regulation of cytosolic calcium ion concentration;blood coagulation;positive regulation of gene expression;negative regulation of gene expression;regulation of primitive erythrocyte differentiation;cell differentiation in hindbrain;commitment of neuronal cell to specific neuron type in forebrain;central nervous system neuron development;pituitary gland development;response to lipid;somatic stem cell population maintenance;regulation of histone acetylation;eosinophil fate commitment;inner ear morphogenesis;positive regulation of mast cell degranulation;negative regulation of fat cell differentiation;positive regulation of erythrocyte differentiation;negative regulation of macrophage differentiation;positive regulation of megakaryocyte differentiation;positive regulation of neuron differentiation;negative regulation of Notch signaling pathway;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;cell maturation;homeostasis of number of cells within a tissue;positive regulation of phagocytosis;positive regulation of phagocytosis, engulfment;definitive hemopoiesis;semicircular canal development;negative regulation of fat cell proliferation;positive regulation of cell migration involved in sprouting angiogenesis;cochlea development;GABAergic neuron differentiation;regulation of hematopoietic stem cell differentiation;positive regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis;negative regulation of neural precursor cell proliferation;negative regulation of endothelial cell apoptotic process;regulation of forebrain neuron differentiation
- Cellular component
- nucleus;nucleoplasm;cytoplasm;protein-containing complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;zinc ion binding;C2H2 zinc finger domain binding