GATA3 Gene: Structure, Function, and Clinical Significance
A comprehensive guide to GATA3, a master regulator of development and a key player in breast cancer and endocrine disorders.
Gene Information Card
| Symbol | GATA3 |
|---|---|
| Full Name | GATA binding protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 10p14 |
| NCBI Gene ID | 2625 ncbi.nlm.nih.gov/gene/2625 |
| Ensembl ID | ENSG00000107485 |
| UniProt ID | P23771 |
| OMIM ID | 131320 |
| HGNC ID | 4172 |
| Aliases | HDRS, MGC2346, MGC5199 |
Description
GATA3 (GATA binding protein 3) is a transcription factor that belongs to the GATA family, characterized by two zinc finger domains that bind to the consensus DNA sequence (A/T)GATA(A/G). It plays a critical role in embryonic development, particularly in the differentiation of T cells, luminal epithelial cells of the mammary gland, and the development of the inner ear, kidney, and parathyroid glands. GATA3 is also a key regulator of gene expression in various tissues and is frequently mutated or dysregulated in cancers, especially breast cancer. Its dual role as a pioneer factor and a lineage-specific regulator makes it a central node in developmental and pathological processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome | Heterozygous loss-of-function mutations in GATA3 lead to haploinsufficiency, disrupting the development of parathyroid glands, inner ear, and kidneys. | OMIM #146255; ClinVar; multiple case reports |
| Breast cancer | GATA3 mutations (mostly missense and frameshift) are common in luminal breast cancer. Loss of function or dominant-negative effects disrupt luminal differentiation and promote tumor progression. | COSMIC; TCGA; multiple studies (e.g., Usary et al., 2004) |
| Endometrial cancer | GATA3 mutations and altered expression are observed, potentially affecting tumor differentiation and prognosis. | COSMIC; TCGA |
| Prostate cancer | GATA3 expression is often reduced, and loss correlates with aggressive disease, suggesting a tumor-suppressive role. | Multiple studies (e.g., Rodriguez-Bravo et al., 2017) |
| T-cell acute lymphoblastic leukemia (T-ALL) | GATA3 mutations and overexpression are implicated in T-cell leukemogenesis, affecting T-cell differentiation. | COSMIC; studies (e.g., Van Vlierberghe et al., 2010) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 12.5 | High |
| Kidney | 8.2 | Medium |
| Skin | 6.1 | Medium |
| Lung | 4.3 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | Luminal-like, high GATA3 expression |
| T-47D (breast cancer) | 14.8 | Luminal-like, high GATA3 expression |
| HepG2 (liver cancer) | 2.1 | Low expression |
| A549 (lung cancer) | 3.4 | Low expression |
| Jurkat (T-cell leukemia) | 10.2 | T-cell lineage, high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.916C>T (p.Arg306Ter) | Nonsense | Rare | Loss of function; associated with HDR syndrome |
| c.808C>T (p.Arg270Ter) | Nonsense | Rare | Loss of function; associated with HDR syndrome |
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare | Loss of function; associated with HDR syndrome |
| c.1102delC (p.Leu368TrpfsTer19) | Frameshift | Rare | Loss of function; associated with HDR syndrome |
| c.404G>A (p.Arg135His) | Missense | Somatic in breast cancer | Altered DNA binding; potential dominant-negative effect |
| c.1253A>G (p.Tyr418Cys) | Missense | Somatic in breast cancer | Altered protein stability; potential loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GATA3 mutations in HDR syndrome are loss-of-function, leading to haploinsufficiency. In breast cancer, frameshift mutations in the second zinc finger often result in truncated proteins with loss of DNA-binding ability.
Gain of Function (GOF)
Gain-of-function mutations are rare but have been reported in some T-ALL cases, leading to enhanced transcriptional activity and promoting leukemogenesis.
Dominant Negative (DN)
Certain missense mutations in the zinc finger domains can exert dominant-negative effects by forming inactive heterodimers with wild-type GATA3, disrupting normal transcriptional regulation.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Chromatin binding | • Protein dimerization activity |
| • Regulation of transcription by RNA polymerase II | • Cell differentiation |
| • Mammary gland development | • T cell differentiation |
| • Inner ear development | • Kidney development |
Pathways
• Th1 and Th2 cell differentiation
• Mammary gland development
• Notch signaling pathway
• TGF-beta signaling pathway
• Estrogen signaling pathway
Protein Summary
GATA3 is a 444-amino acid protein with two conserved zinc finger domains (Cys-X2-Cys-X17-Cys-X2-Cys) that mediate sequence-specific DNA binding and protein-protein interactions. The N-terminal zinc finger is involved in stabilizing DNA binding and interacting with cofactors, while the C-terminal zinc finger is essential for high-affinity binding to GATA motifs. GATA3 functions as a pioneer factor, opening chromatin and facilitating the binding of other transcription factors. It is critical for the differentiation of T helper 2 (Th2) cells, luminal epithelial cells in the breast, and the development of the parathyroid, inner ear, and kidney. Post-translational modifications, such as phosphorylation and acetylation, regulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GATA3 Knockout HEK293 Cell Line | EDJ-KQ1017 | Human | 2625 | Details Get a Quote |
| GATA3 Knockout A-549 Cell Line | EDJ-KQ20091 | Human | 2625 | Details Get a Quote |
| GATA3 Knockout HCT 116 Cell Line | EDJ-KQ20092 | Human | 2625 | Details Get a Quote |
| GATA3 Knockout HeLa Cell Line | EDJ-KQ53307 | Human | 2625 | Details Get a Quote |
| GATA3 (p.A207=) Point Mutation in HAP1 Cell Line | EDC03497 | Human | 2625 | Details Get a Quote |
| GATA3 (c.925-27C>T )Point Mutation in HAP1 Cell Line | EDC03498 | Human | 2625 | Details Get a Quote |
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