GATA6 Gene: Structure, Function, and Clinical Significance
A master transcription factor in cardiac, pancreatic, and pulmonary development, with implications in congenital heart disease and pancreatic agenesis.
Gene Information Card
| Symbol | GATA6 |
|---|---|
| Full Name | GATA binding protein 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q11.2 |
| NCBI Gene ID | 2625 ncbi.nlm.nih.gov/gene/2625 |
| Ensembl ID | ENSG00000141448 |
| UniProt ID | Q92908 |
| OMIM ID | 601656 |
| HGNC ID | 4174 |
| Aliases | MGC117343, MGC126697, MGC126699 |
Description
GATA6 encodes a member of the GATA family of zinc-finger transcription factors. This protein plays a critical role in the development of several organ systems, including the heart, pancreas, lungs, and gut. It regulates gene expression by binding to the consensus DNA sequence (A/T)GATA(A/G) and interacts with other transcription factors to control cell differentiation and morphogenesis. Mutations in GATA6 are associated with congenital heart defects, pancreatic agenesis, and other developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital heart disease (CHD) | Heterozygous loss-of-function mutations impair cardiac gene regulatory networks, leading to septal defects, conotruncal anomalies, and other structural malformations. | ClinVar, OMIM |
| Pancreatic agenesis | Biallelic or heterozygous mutations disrupt pancreatic progenitor specification, resulting in complete or partial absence of the pancreas. | OMIM, PubMed |
| Atrial septal defect (ASD) | Mutations in GATA6 alter expression of downstream targets like NKX2-5, contributing to septation defects. | ClinVar, PubMed |
| Tetralogy of Fallot | Loss-of-function variants reduce GATA6 transcriptional activity, affecting cardiac outflow tract development. | ClinVar, PubMed |
| Pulmonary hypertension | GATA6 mutations may affect pulmonary vascular remodeling, though evidence is emerging. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 20.1 | Medium |
| Pancreas | 15.3 | Medium |
| Lung | 12.8 | Medium |
| Liver | 8.5 | Low |
| Small intestine | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 18.2 | Moderate expression |
| A549 (lung) | 12.5 | Moderate expression |
| PANC-1 (pancreas) | 10.3 | Moderate expression |
| K562 (leukemia) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1062C>A (p.Tyr354Ter) | Nonsense | Rare | Loss-of-function; associated with pancreatic agenesis and CHD |
| c.820G>A (p.Glu274Lys) | Missense | Rare | Loss-of-function; reduced transcriptional activity, linked to CHD |
| c.1138C>T (p.Arg380Trp) | Missense | Rare | Dominant-negative effect; associated with tetralogy of Fallot |
| c.1334G>A (p.Arg445His) | Missense | Rare | Loss-of-function; reported in atrial septal defect |
Mutation functional classification
Loss of Function (LOF)
Most GATA6 mutations are heterozygous loss-of-function, leading to haploinsufficiency. These mutations impair DNA binding or transcriptional activation, disrupting downstream gene networks essential for organ development.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well-documented for GATA6. Some variants may enhance transcriptional activity, but their clinical significance is unclear.
Dominant Negative (DN)
Certain missense mutations, such as p.Arg380Trp, exhibit dominant-negative effects by interfering with the function of the wild-type allele, potentially worsening the phenotype.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • zinc ion binding | • regulation of transcription by RNA polymerase II |
| • heart development | • pancreas development |
| • lung development | • cell differentiation |
Pathways
• Cardiac progenitor differentiation
• Pancreatic beta-cell development
• Endodermal cell fate specification
• TGF-beta signaling (interaction with SMADs)
Protein Summary
GATA6 is a 595-amino acid protein containing two conserved zinc-finger domains that mediate sequence-specific DNA binding. It is essential for the differentiation of endodermal and mesodermal derivatives. The protein interacts with other transcription factors such as NKX2-5, FOXA2, and GATA4 to regulate tissue-specific gene expression. Post-translational modifications, including acetylation and phosphorylation, modulate its activity. GATA6 is critical for cardiac morphogenesis, pancreatic endocrine cell formation, and lung epithelial differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GATA6 Knockout HEK293 Cell Line | EDJ-KQ2555 | Human | 2627 | Details Get a Quote |
| GATA6 Knockout A-549 Cell Line | EDJ-KQ23208 | Human | 2627 | Details Get a Quote |
| GATA6 Knockout HCT 116 Cell Line | EDJ-KQ23209 | Human | 2627 | Details Get a Quote |
| GATA6 Knockout HeLa Cell Line | EDJ-KQ23210 | Human | 2627 | Details Get a Quote |
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