FOXA1 (Forkhead Box A1): Pioneer Transcription Factor in Hormone-Dependent Cancers
A master regulator of chromatin accessibility and hormone receptor signaling, frequently altered in breast and prostate cancers.
Gene Information Card
| Symbol | FOXA1 |
|---|---|
| Full Name | Forkhead Box A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q21.1 |
| NCBI Gene ID | 3169 ncbi.nlm.nih.gov/gene/3169 |
| Ensembl ID | ENSG00000129514 |
| UniProt ID | P55317 |
| OMIM ID | 602294 |
| HGNC ID | 5021 |
| Aliases | HNF3A, TCF3A, MGC33105 |
Description
FOXA1 (Forkhead Box A1), also known as HNF3A, encodes a member of the forkhead class of DNA-binding proteins. As a pioneer transcription factor, FOXA1 binds to condensed chromatin and opens it, facilitating the recruitment of other transcription factors, particularly hormone receptors like estrogen receptor (ER) and androgen receptor (AR). It is essential for normal development of the liver, lung, prostate, and mammary gland. FOXA1 is frequently mutated or overexpressed in several cancers, especially hormone-dependent breast and prostate cancers, where it influences tumor progression and therapy response.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | FOXA1 mutations and overexpression alter ER binding and gene expression, promoting tumor growth and endocrine resistance. | COSMIC, ClinVar, multiple studies |
| Prostate Cancer | FOXA1 mutations and gene fusions (e.g., with AR) enhance AR signaling and drive castration-resistant prostate cancer. | COSMIC, ClinVar, multiple studies |
| Hepatocellular Carcinoma | FOXA1 overexpression is associated with poor prognosis and may promote epithelial-mesenchymal transition. | COSMIC, literature |
| Lung Cancer | FOXA1 expression is elevated in lung adenocarcinoma and may contribute to tumor progression. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 20.1 | Medium |
| Prostate | 15.3 | Medium |
| Liver | 12.4 | Medium |
| Lung | 8.2 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast) | 35.2 | ER-positive breast cancer cell line |
| LNCaP (Prostate) | 28.7 | Androgen-sensitive prostate cancer cell line |
| HepG2 (Liver) | 22.4 | Hepatocellular carcinoma cell line |
| A549 (Lung) | 10.3 | Lung adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R219C | Missense | ~2% in breast cancer | Alters DNA binding affinity |
| F266L | Missense | ~1% in prostate cancer | Affects protein stability |
| G259V | Missense | ~1% in breast cancer | Impairs forkhead domain function |
| Amplification | Copy number gain | ~10% in breast cancer | Increased expression |
Mutation functional classification
Loss of Function (LOF)
Rare truncating mutations that impair DNA binding or nuclear localization, leading to reduced pioneer activity.
Gain of Function (GOF)
Missense mutations in the forkhead domain that enhance chromatin opening and alter target gene selection, promoting oncogenic signaling.
Dominant Negative (DN)
Some mutations may produce a protein that competes with wild-type FOXA1, disrupting normal pioneer function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • Chromatin binding |
| • Sequence-specific DNA binding | • Regulation of transcription by RNA polymerase II |
| • Cell differentiation | • Response to hormone |
Pathways
• Estrogen receptor signaling
• Androgen receptor signaling
• Chromatin remodeling
• Developmental biology
Protein Summary
FOXA1 is a 472-amino acid protein with a conserved forkhead DNA-binding domain. It binds to the consensus sequence 5'-T[G/A]TTT[G/A]T-3' in the minor groove of DNA, acting as a pioneer factor to open condensed chromatin. This enables recruitment of hormone receptors and other transcription factors. FOXA1 is critical for normal organ development and is implicated in cancer progression, particularly in hormone-driven tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXA1 Knockout HEK293 Cell Line | EDJ-KQ2840 | Human | 3169 | Details Get a Quote |
| FOXA1 Knockout A-549 Cell Line | EDJ-KQ23832 | Human | 3169 | Details Get a Quote |
| FOXA1 Knockout HCT 116 Cell Line | EDJ-KQ23833 | Human | 3169 | Details Get a Quote |
| FOXA1 Knockout HeLa Cell Line | EDJ-KQ23834 | Human | 3169 | Details Get a Quote |
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