FOXA2 Gene - Forkhead Box A2
Key regulator of embryonic development, metabolism, and cell differentiation
Gene Information Card
| Symbol | FOXA2 |
|---|---|
| Full Name | Forkhead Box A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p11.21 |
| NCBI Gene ID | 3170 ncbi.nlm.nih.gov/gene/3170 |
| Ensembl ID | ENSG00000125798 |
| UniProt ID | Q9Y261 |
| OMIM ID | 600288 |
| HGNC ID | 5022 |
| Aliases | HNF3B, TCF3B, MGC111102 |
Description
FOXA2 (Forkhead Box A2) is a transcription factor belonging to the forkhead family, characterized by a conserved DNA-binding forkhead domain. It acts as a pioneer factor, opening compacted chromatin to facilitate binding of other transcription factors. FOXA2 is essential for embryonic development, particularly of the endoderm-derived organs such as liver, pancreas, and lung. It regulates glucose homeostasis, lipid metabolism, and cell differentiation. Dysregulation of FOXA2 is implicated in metabolic disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young (MODY) | Loss-of-function mutations in FOXA2 impair pancreatic beta-cell development and insulin secretion, leading to monogenic diabetes. | ClinVar, OMIM |
| Hepatocellular Carcinoma | FOXA2 acts as a tumor suppressor; reduced expression promotes hepatocyte proliferation and dedifferentiation. | COSMIC, NCBI |
| Lung Adenocarcinoma | FOXA2 overexpression drives oncogenic transcriptional programs, promoting cell proliferation and invasion. | COSMIC, PubMed |
| Congenital Hyperinsulinism | FOXA2 mutations disrupt pancreatic islet cell differentiation, causing dysregulated insulin secretion. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 42.3 | High |
| Pancreas | 38.1 | High |
| Lung | 25.7 | Medium |
| Kidney | 12.4 | Medium |
| Stomach | 8.9 | Low |
| Small Intestine | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 45.1 | Hepatocellular carcinoma cell line |
| PANC-1 | 32.8 | Pancreatic ductal adenocarcinoma cell line |
| A549 | 28.4 | Lung adenocarcinoma cell line |
| HEK 293 | 2.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.910C>T (p.Arg304*) | Nonsense | Rare | Loss of function; associated with MODY |
| c.1045G>A (p.Gly349Arg) | Missense | Rare | Impaired DNA binding; dominant negative effect |
| c.1282C>T (p.Arg428Cys) | Missense | Rare | Reduced transcriptional activity; linked to hyperinsulinism |
| c.1462_1463del (p.Leu488fs) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg304*, p.Leu488fs) result in truncated, non-functional FOXA2 protein, impairing target gene activation.
Gain of Function (GOF)
Missense mutations in the forkhead domain (e.g., p.Gly349Arg) can alter DNA-binding specificity, potentially activating oncogenic pathways.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Gly349Arg) produce a protein that interferes with wild-type FOXA2 function, reducing overall transcriptional activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) |
| • Chromatin binding (GO:0003682) | • Positive regulation of transcription by RNA polymerase II (GO:0045944) |
| • Liver development (GO:0001889) | • Pancreas development (GO:0031016) |
| • Glucose homeostasis (GO:0042593) |
Pathways
• Hepatocyte nuclear factor (HNF) network
• Endoderm differentiation
• Insulin signaling pathway
• Glucagon signaling pathway
• Metabolic pathways
Protein Summary
FOXA2 is a 463-amino acid transcription factor with a central forkhead DNA-binding domain. It binds to the consensus sequence 5'-T(A/G)TTT(G/A)(C/T)T-3' and functions as a pioneer factor, enabling chromatin remodeling. The protein contains N-terminal and C-terminal transactivation domains. Post-translational modifications include phosphorylation and acetylation, which modulate its activity. FOXA2 is critical for endoderm-derived organogenesis and metabolic regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXA2 Knockout HEK293 Cell Line | EDJ-KQ2898 | Human | 3170 | Details Get a Quote |
| FOXA2 Knockout HeLa Cell Line | EDJ-KQ53536 | Human | 3170 | Details Get a Quote |
| FOXA2 Knockout A-549 Cell Line | EDJ-KQ62010 | Human | 3170 | Details Get a Quote |
| FOXA2 Knockout HCT 116 Cell Line | EDJ-KQ70487 | Human | 3170 | Details Get a Quote |
| FOXA2 Knockout BEAS-2B Cell Line | EDC90242 | Human | 3170 | Details Get a Quote |
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