GeneBe

GATA1

protein-coding

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

Gene summary

This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]

Previous symbols:
  • GF1

MANE transcript

NM_002049.4

Inheritance

XL, AD, AR

ClinVar variants

P:91U:191B:131

Top phenotype

Thrombocytopenia with beta-thalessemia, X-linked; Anemia, X-linked, with or without thrombocytopenia and platelet abnormalities; Dyserythropoietic anemia with thrombocytopenia; Anemia, congenital, nonspherocytic hemolytic, 9

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:48,786,540-48,794,311

External References & Databases

Ensembl (ENSG00000102145)NCBI Gene (2623)OMIM (305371)HGNC:4170GenCCUniProt (P15976)AlphaFoldClinVar (GATA1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

beta-thalassemia-X-linked thrombocytopenia syndromeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010745

Submitter: Orphanet

Diamond-Blackfan anemiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015253

Submitter: Orphanet

congenital erythropoietic porphyriaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009902

Submitter: Orphanet

thrombocytopenia, X-linked, with or without dyserythropoietic anemiaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010308

Submitter: Labcorp Genetics (formerly Invitae)

thrombocytopenia, X-linked, with or without dyserythropoietic anemiaMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010308

Submitter: Genomics England PanelApp

thrombocytopenia with congenital dyserythropoietic anemiaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0019031

Submitter: Orphanet

GATA1-related cytopeniaDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0100089

Submitter: ClinGen

GATA1 was first reported in relation to GATA1-related X-linked cytopenia in 2000 (Nichols et al, PMID: 10700180), however the disorder was termed familial dyserythropoietic anemia and thrombocytopenia. Subsequently, other terms including X-linked thrombocytopenia with beta-thalassemia, X-linked thrombocytopenia with or without dyserythropoietic anemia, X-linked macrothrombocytopenia, and X-linked anemia with or without neutropenia and/or platelet abnormalities have been used. GATA1-related cytopenia is the accepted term to encompass the heterogeneity of this disorder (Chou et al, 2017, PMID: 20301538). Evidence supporting this gene-disease curation includes case-level data, segregation data, and experimental data. At least 13 unique variants (missense and splicing) have been reported in humans. Variants in this gene have been reported in at least 23 probands in over 20 publications. Variants in this gene segregated with disease in 22 additional family members. The gene disease relationship is supported by animal models (PMID: 8901585; 14656885; 11566888), functional alteration in patient and non-patient cells (PMID: 25621499; 23704091; 12200364; 10700180) and protein interaction studies (PMID: 9230307). Additionally, the GATA1 p.Arg216Trp variant has been associated with three cases of X-linked congenital erythropoietic porphyria, which shares significant phenotypic overlap with GATA1-related cytopenia (PMID:25251786, 17148589). In summary, GATA1 is definitively associated with GATA1-related X-linked cytopenia. This has been repeatedly demonstrated in both the research and the clinical diagnostic settings and has been upheld over time. This curation was approved as a definitive association by the Hemostasis/Thrombosis GCEP on May 27, 2020.

beta-thalassemia-X-linked thrombocytopenia syndromeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010745

Submitter: Ambry Genetics

Diamond-Blackfan anemiaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0015253

Submitter: PanelApp Australia

X-linked dyserythropoetic anemia with abnormal platelets and neutropeniaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010444

Submitter: Orphanet

Clinical Genomic Database (CGD)

Thrombocytopenia with beta-thalessemia, X-linked; Anemia, X-linked, with or without thrombocytopenia and platelet abnormalities; Dyserythropoietic anemia with thrombocytopenia; Anemia, congenital, nonspherocytic hemolytic, 9XL

Manifestation: Hematologic

Intervention: Hematologic; Pharmacogenomic

Rationale: 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 Anemia, congenital, nonspherocytic hemolytic, 9 have been reported as requiring RBC transfusions

Refs: 871527; 10700180; 11418466; 11675338; 11809723; 12200364; 17209061; 20301538; 22102271; 35030251Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GATA1 variants in ClinVar

22 Conditions Cataloged
GATA binding protein 1 related thrombocytopenia with dyserythropoiesisTotal: 349
Diamond-Blackfan anemiaTotal: 347
not providedTotal: 80
GATA1-related disorderTotal: 53
not specifiedTotal: 38
Inborn genetic diseasesTotal: 29
Thrombocytopenia, X-linked, with or without dyserythropoietic anemiaTotal: 29
X-linked dyserythropoetic anemia with abnormal platelets and neutropeniaTotal: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002049.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
84
clinvar
8
clinvar
 96
missense
7
clinvar
11
clinvar
180
clinvar
32
clinvar
7
clinvar
 237
nonsense
5
clinvar
3
clinvar
2
clinvar
 10
start loss
3
clinvar
3
clinvar
 6
frameshift
39
clinvar
12
clinvar
3
clinvar
 54
splice donor/acceptor (+/-2bp)
4
clinvar
3
clinvar
3
clinvar
 10
Total583319111615413

Highest pathogenic variant AF is 0.0000089508685

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002049.4RefSeqNP_002040.15MANE Select
ENST00000376670.9EnsemblENSP00000365858.35MANE Select
ENST00000376665.4EnsemblENSP00000365853.35Standard
ENST00000376665.5EnsemblENSP00000365853.35Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gata1aDanio rerio

Structure: myeloid cell

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Hematopoietic Stem Cell Differentiation
  • Gene expression (Transcription)
  • hemoglobins chaperone
  • Generic Transcription Pathway
  • Factors involved in megakaryocyte development and platelet production

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • in utero embryonic development
  • transcription by RNA polymerase II
  • cell-cell signaling
  • blood coagulation

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

Cellular Component

  • nucleus
  • nucleoplasm
  • transcription factor complex
  • transcriptional repressor complex
  • protein-DNA complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000376670
Coding exons
5
Length
7755
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.141331750.7590.00001432583
Missense (PolyPhen)4372.2940.59481046
Synonymous0.1087576.20.9840.00000634959
Loss of Function2.8309.320.006.44e-7164

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.709

Intolerance Scores

LoFtool
0.0369
RVIS EVS
-0.6
RVIS percentile EVS
17.75

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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