FOXM1 Gene: Forkhead Box M1 - Function, Disease Associations, and Expression
A comprehensive biomedical overview of the FOXM1 gene, including genomic context, protein function, expression profiles, and clinical significance.
Gene Information Card
| Symbol | FOXM1 |
|---|---|
| Full Name | Forkhead Box M1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 2305 ncbi.nlm.nih.gov/gene/2305 |
| Ensembl ID | ENSG00000111206 |
| UniProt ID | Q08050 |
| OMIM ID | 602341 |
| HGNC ID | 3818 |
| Aliases | FKHL16, HFH-11, MPP2, WIN, INS-1, MPP-2 |
Description
FOXM1 (Forkhead Box M1) is a transcription factor belonging to the forkhead family, characterized by a conserved DNA-binding forkhead domain. It plays a critical role in cell cycle progression, particularly the G1/S and G2/M transitions, by regulating the expression of genes involved in mitosis, DNA repair, and chromosome segregation. FOXM1 is highly expressed in proliferating cells and is frequently overexpressed in various cancers, contributing to tumorigenesis, metastasis, and drug resistance. Its expression is tightly regulated during the cell cycle, peaking in S and G2 phases, and is controlled by multiple signaling pathways including RAS/MAPK, PI3K/AKT, and WNT. FOXM1 also interacts with key cell cycle regulators such as cyclin-dependent kinases (CDKs) and is a target of the tumor suppressor p53. Due to its pivotal role in cell proliferation and cancer, FOXM1 is considered a potential therapeutic target and prognostic biomarker.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Overexpression promotes cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) via transcriptional activation of target genes like c-Myc and MMPs. | High expression correlates with poor prognosis; functional studies show knockdown reduces tumor growth in xenograft models. |
| Breast cancer | FOXM1 overexpression drives cell cycle progression and resistance to endocrine therapy; it regulates genes involved in DNA repair and stemness. | Clinical samples show elevated FOXM1 in aggressive subtypes; inhibition sensitizes cells to chemotherapy. |
| Non-small cell lung cancer | FOXM1 promotes proliferation and metastasis by upregulating genes like AURKB and CDC25B; also involved in EMT. | Expression is associated with advanced stage and poor survival; siRNA knockdown reduces invasion. |
| Glioblastoma | FOXM1 is overexpressed and contributes to tumor aggressiveness by enhancing proliferation and inhibiting apoptosis. | Inhibition of FOXM1 reduces tumor growth in orthotopic models and increases sensitivity to temozolomide. |
| Prostate cancer | FOXM1 regulates androgen receptor signaling and promotes castration-resistant growth. | High FOXM1 expression correlates with recurrence; targeting FOXM1 suppresses tumor growth in vivo. |
| Pancreatic cancer | FOXM1 overexpression enhances proliferation, migration, and chemoresistance through activation of EMT and stemness pathways. | Expression is elevated in pancreatic ductal adenocarcinoma; knockdown reduces tumor formation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thymus | 12.3 | Medium |
| Testis | 8.7 | Low |
| Bone marrow | 6.5 | Low |
| Spleen | 4.2 | Low |
| Lung | 2.1 | Low |
| Liver | 1.5 | Not detected |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.4 | Cervical carcinoma; high expression |
| MCF7 | 18.2 | Breast cancer; elevated |
| A549 | 15.7 | Lung cancer; high |
| HepG2 | 12.9 | Liver cancer; moderate |
| K562 | 8.3 | Leukemia; moderate |
| U2OS | 6.1 | Osteosarcoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.5% in COSMIC | Alters DNA-binding affinity; potential gain-of-function in cancer. |
| c.1567G>A (p.Val523Met) | Missense | 0.3% in COSMIC | Located in transactivation domain; may affect protein stability. |
| c.2010delC (p.Pro670LeufsTer3) | Frameshift | 0.1% in COSMIC | Truncates protein; likely loss-of-function. |
| c.789_790insA (p.Gln264ThrfsTer12) | Insertion | 0.2% in COSMIC | Premature stop; loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, leading to loss of transcriptional activity and reduced cell proliferation.
Gain of Function (GOF)
Missense mutations in the DNA-binding domain that enhance binding affinity or transactivation, promoting oncogenic activity.
Dominant Negative (DN)
Mutations that produce a truncated protein lacking the transactivation domain but retaining DNA-binding, interfering with wild-type FOXM1 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein binding | • chromatin binding |
| • cell cycle | • regulation of cell cycle |
| • mitotic cell cycle | • DNA damage response |
| • cell proliferation | • positive regulation of transcription by RNA polymerase II |
Pathways
• Cell Cycle
• Mitotic
• G2/M Transition
• FoxO signaling pathway
• Pathways in cancer
• Hepatitis B
• Proteoglycans in cancer
• MicroRNAs in cancer
Protein Summary
FOXM1 is a 110 kDa transcription factor with a conserved forkhead DNA-binding domain and a C-terminal transactivation domain. It exists in multiple isoforms due to alternative splicing, with the most common being FOXM1b and FOXM1c. The protein is phosphorylated by cyclin-dependent kinases (CDKs) and Polo-like kinase 1 (PLK1), which regulate its nuclear localization and transcriptional activity. FOXM1 binds to the consensus sequence 5'-A/TAACA/TA-3' in promoter regions of target genes, activating genes essential for mitosis (e.g., Cyclin B1, Cdc25B, Aurora B) and DNA repair (e.g., BRCA2, XRCC1). It also interacts with other proteins such as β-catenin and SMAD3 to modulate gene expression. FOXM1 is degraded via the ubiquitin-proteasome pathway, and its stability is regulated by the APC/C complex. In cancer, FOXM1 is often overexpressed due to genomic amplification, transcriptional activation by oncogenic pathways, or reduced degradation, leading to uncontrolled proliferation and therapy resistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXM1 Knockout HEK293 Cell Line | EDJ-KQ2819 | Human | 2305 | Details Get a Quote |
| FOXM1 Knockout A-549 Cell Line | EDJ-KQ23783 | Human | 2305 | Details Get a Quote |
| FOXM1 Knockout HCT 116 Cell Line | EDJ-KQ23784 | Human | 2305 | Details Get a Quote |
| FOXM1 Knockout HeLa Cell Line | EDJ-KQ23785 | Human | 2305 | Details Get a Quote |
