GATA1

GATA binding protein 1, the group of GATA zinc finger domain containing

Basic information

Region (hg38): X:48786539-48794311

Previous symbols: [ "GF1" ]

Links

ENSG00000102145 ∙ NCBI:2623 ∙ OMIM:305371 ∙ HGNC:4170 ∙ Uniprot:P15976 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombocytopenia, X-linked, with or without dyserythropoietic anemia (Moderate), mode of inheritance: XL
• beta-thalassemia-X-linked thrombocytopenia syndrome (Moderate), mode of inheritance: XL
• Diamond-Blackfan anemia (Supportive), mode of inheritance: AD
• thrombocytopenia with congenital dyserythropoietic anemia (Supportive), mode of inheritance: XL
• cutaneous porphyria (Supportive), mode of inheritance: AR
• beta-thalassemia-X-linked thrombocytopenia syndrome (Supportive), mode of inheritance: XL
• X-linked dyserythropoetic anemia with abnormal platelets and neutropenia (Supportive), mode of inheritance: XL
• thrombocytopenia, X-linked, with or without dyserythropoietic anemia (Strong), mode of inheritance: XL
• GATA1-Related X-Linked Cytopenia (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia with beta-thalessemia, X-linked; Anemia, X-linked, with or without thrombocytopenia and platelet abnormalities; Dyserythropoietic anemia with thrombocytopenia; Hemolytic anemia due to elevated adenosine deaminase	XL	Hematologic; Pharmacogenomic	Individuals, especially males (though females have been reported with bleeding complications, such as in the postpartum period), may require preventive measures and treatment (eg, with platelet and/or RBC transfusions) related to bleeding diathesis; Certain activities and agents (eg, contact sports and medications such as NSAIDS) should be avoided in some individuals; BMT has been reported; Individuals with Hemolytic anemia due to elevated adenosine deaminase have been reported as requiring RBC transfusions	Hematologic	871527; 10700180; 11418466; 11675338; 11809723; 12200364; 17209061; 20301538; 22102271; 35030251

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GATA1 gene.

• Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis (97 variants)
• GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia (96 variants)
• not provided (36 variants)
• not specified (14 variants)
• Thrombocytopenia, X-linked, with or without dyserythropoietic anemia (12 variants)
• GATA1-related condition (7 variants)
• Acute megakaryoblastic leukemia in down syndrome (6 variants)
• X-linked dyserythropoetic anemia with abnormal platelets and neutropenia (5 variants)
• Transient myeloproliferative syndrome (4 variants)
• Inborn genetic diseases (4 variants)
• Thrombocytopenia (3 variants)
• Beta-thalassemia-X-linked thrombocytopenia syndrome (3 variants)
• Macrothrombocytopenia (2 variants)
• Complete trisomy 21 syndrome;Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;Beta-thalassemia-X-linked thrombocytopenia syndrome;X-linked dyserythropoetic anemia with abnormal platelets and neutropenia (2 variants)
• Hemolytic anemia due to erythrocyte adenosine deaminase overproduction (2 variants)
• X-linked dyserythropoetic anemia with abnormal platelets and neutropenia;Complete trisomy 21 syndrome;Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;Beta-thalassemia-X-linked thrombocytopenia syndrome (2 variants)
• Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;X-linked dyserythropoetic anemia with abnormal platelets and neutropenia;Complete trisomy 21 syndrome;Beta-thalassemia-X-linked thrombocytopenia syndrome (1 variants)
• Acute megakaryoblastic leukemia (1 variants)
• Cutaneous porphyria (1 variants)
• Complete trisomy 21 syndrome;Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;X-linked dyserythropoetic anemia with abnormal platelets and neutropenia;Beta-thalassemia-X-linked thrombocytopenia syndrome (1 variants)
• GATA binding protein 1 related thrombocytopenia with dyserythropoiesis (1 variants)
• Complete trisomy 21 syndrome (1 variants)
• Thrombocytopenia, X-linked, without dyserythropoietic anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GATA1 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			2	41	10	53
missense	5	5	90	6	11	117
nonsense	3	2	1			6
start loss	2					2
frameshift	24	2	2			28
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region	1		1	2	3	7
non coding				8	4	12
Total	35	12	97	55	25

Highest pathogenic variant AF is 0.00000895

Variants in GATA1

This is a list of pathogenic ClinVar variants found in the GATA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-48791018-A-AG			Benign (Jul 08, 2018)
X-48791049-G-G			Benign (Aug 06, 2019)
X-48791079-C-T		GATA1-related disorder	Likely benign (Sep 28, 2020)
X-48791086-C-T		not specified	Likely benign (-)
X-48791103-AGGCTCCATGGAGTTCCCTGGCCTGG-A		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Pathogenic (Oct 14, 2023)
X-48791111-T-C		Thrombocytopenia, X-linked, with or without dyserythropoietic anemia • X-linked dyserythropoetic anemia with abnormal platelets and neutropenia • Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Pathogenic (Feb 18, 2023)
X-48791111-T-TG		Transient myeloproliferative syndrome	Pathogenic (Sep 01, 2020)
X-48791112-G-T		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Pathogenic (Feb 11, 2020)
X-48791113-G-GAGTT		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Pathogenic (Nov 16, 2018)
X-48791126-TG-T		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Pathogenic (Sep 03, 2017)
X-48791128-G-C		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Uncertain significance (Mar 13, 2022)
X-48791144-C-G		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis • Complete trisomy 21 syndrome;Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;X-linked dyserythropoetic anemia with abnormal platelets and neutropenia;Beta-thalassemia-X-linked thrombocytopenia syndrome • GATA1-related disorder	Pathogenic/Likely pathogenic (Sep 28, 2023)
X-48791148-G-A		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Likely benign (Nov 12, 2021)
X-48791150-C-A		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Uncertain significance (Oct 03, 2023)
X-48791150-C-T		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Uncertain significance (Nov 29, 2022)
X-48791157-C-A		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Likely benign (Jan 14, 2024)
X-48791157-CCA-C		Transient myeloproliferative syndrome	Pathogenic (Sep 01, 2020)
X-48791158-C-T		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Pathogenic (Jul 01, 2019)
X-48791160-G-C		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Uncertain significance (Dec 10, 2022)
X-48791170-C-T		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Uncertain significance (Feb 16, 2023)
X-48791173-G-A		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Benign (Apr 25, 2023)
X-48791174-C-G		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Benign (Nov 15, 2023)
X-48791177-T-G		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Uncertain significance (Oct 13, 2023)
X-48791177-T-TGGTGTCCTCCACACCAGAATCA		GATA binding protein 1 related thrombocytopenia with dyserythropoiesis;Diamond-Blackfan anemia	Pathogenic (Feb 18, 2023)
X-48791189-C-T		Diamond-Blackfan anemia;GATA binding protein 1 related thrombocytopenia with dyserythropoiesis	Uncertain significance (Aug 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GATA1	protein_coding	protein_coding	ENST00000376670	5	7755

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.948	0.0519	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	133	175	0.759	0.0000143	2583
Missense in Polyphen		43	72.294	0.5948		1046
Synonymous	0.108	75	76.2	0.984	0.00000634	959
Loss of Function	2.83	0	9.32	0.00	6.44e-7	164

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator or repressor which probably serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of globin genes and of other genes expressed in erythroid cells. Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, including HBB, HBG1/2, ALAS2 and HMBS (PubMed:24245781). {ECO:0000269|PubMed:22235304, ECO:0000269|PubMed:24245781}.
• Disease: DISEASE: X-linked dyserythropoietic anemia and thrombocytopenia (XDAT) [MIM:300367]: Disorder characterized by erythrocytes with abnormal size and shape, and paucity of platelets in peripheral blood. The bone marrow contains abundant and abnormally small megakaryocytes. {ECO:0000269|PubMed:10700180, ECO:0000269|PubMed:11418466, ECO:0000269|PubMed:11675338, ECO:0000269|PubMed:11809723}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thrombocytopenia with beta-thalassemia, X-linked (XLTT) [MIM:314050]: An unusual form of thrombocytopenia associated with beta-thalassemia. Patients have splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and unbalanced (hemo)globin chain synthesis resembling that of beta-thalassemia minor. {ECO:0000269|PubMed:12200364}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Anemia without thrombocytopenia, X-linked (XLAWT) [MIM:300835]: A form of anemia characterized by abnormal morphology of erythrocytes and granulocytes in peripheral blood, bone marrow dysplasia with hypocellularity of erythroid and granulocytic lineages, and normal or increased number of megakaryocytes. Neutropenia of a variable degree is present in affected individuals. {ECO:0000269|PubMed:16783379}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hematopoietic Stem Cell Differentiation;Gene expression (Transcription);hemoglobins chaperone;Generic Transcription Pathway;Factors involved in megakaryocyte development and platelet production;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;p73 transcription factor network;Signaling events mediated by HDAC Class II;Hemostasis;C-MYB transcription factor network;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Notch-mediated HES/HEY network;Transcriptional regulation by RUNX1;Signaling events mediated by HDAC Class I (Consensus)

Recessive Scores

• pRec: 0.709

Intolerance Scores

• loftool: 0.0369
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.75

Haploinsufficiency Scores

• pHI: 0.337
• hipred: Y
• hipred_score: 0.697
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• 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: Gata1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; hematopoietic system 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); 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); embryo phenotype

Zebrafish Information Network

• Gene name: gata1a
• Affected structure: myeloid cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;transcription by RNA polymerase II;cell-cell signaling;blood coagulation;negative regulation of cell population proliferation;male gonad development;regulation of glycoprotein biosynthetic process;regulation of definitive erythrocyte differentiation;regulation of primitive erythrocyte differentiation;erythrocyte differentiation;megakaryocyte differentiation;platelet formation;basophil differentiation;eosinophil differentiation;negative regulation of bone mineralization;positive regulation of osteoblast proliferation;embryonic hemopoiesis;eosinophil fate commitment;negative regulation of apoptotic process;positive regulation of erythrocyte differentiation;regulation of megakaryocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;erythrocyte development;homeostasis of number of cells within a tissue;positive regulation of peptidyl-tyrosine phosphorylation;platelet aggregation;transcriptional activation by promoter-enhancer looping;dendritic cell differentiation;cellular response to thyroid hormone stimulus;regulation of hematopoietic stem cell differentiation;negative regulation of transcription regulatory region DNA binding;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;nucleoplasm;transcription factor complex;transcriptional repressor complex;protein-DNA complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;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;RNA polymerase II transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;p53 binding;DNA binding;DNA-binding transcription factor activity;protein binding;zinc ion binding;chromatin DNA binding;sequence-specific DNA binding;C2H2 zinc finger domain binding