FOXM1

Summary

FOXM1 (forkhead box M1, HGNC:3818) is a protein-coding gene on chromosome 12p13.33, encoding Forkhead box protein M1 (Q08050). Transcription factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. It is a selective cancer dependency (DepMap: 16.5% of cell lines).

The protein encoded by this gene is a transcriptional activator involved in cell proliferation. The encoded protein is phosphorylated in M phase and regulates the expression of several cell cycle genes, such as cyclin B1 and cyclin D1. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2305 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 204 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 16.5% of screened cell lines
• Transcription factor: yes — 121 downstream targets (CollecTRI)
• MANE Select transcript: NM_021953

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3818
Approved symbol	FOXM1
Name	forkhead box M1
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	HFH-11, trident, HNF-3, INS-1, MPP2, MPHOSPH2, TGT3
Ensembl gene	ENSG00000111206
Ensembl biotype	protein_coding
OMIM	602341
Entrez	2305

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 26 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000342628, ENST00000359843, ENST00000361953, ENST00000366362, ENST00000535350, ENST00000536066, ENST00000537018, ENST00000538564, ENST00000545049, ENST00000627656, ENST00000865631, ENST00000865632, ENST00000865633, ENST00000917184, ENST00000917185, ENST00000917186, ENST00000917187, ENST00000917188, ENST00000917189, ENST00000917190, ENST00000917191, ENST00000917192, ENST00000917193, ENST00000917194, ENST00000917195, ENST00000917196, ENST00000917197, ENST00000917198, ENST00000917199, ENST00000917200, ENST00000917201

RefSeq mRNA: 23 — MANE Select: NM_021953 NM_001243088, NM_001243089, NM_001413925, NM_001413926, NM_001413927, NM_001413928, NM_001413929, NM_001413930, NM_001413931, NM_001413932, NM_001413933, NM_001413934, NM_001413935, NM_001413936, NM_001413937, NM_001413938, NM_001413939, NM_001413940, NM_001413941, NM_001413942, NM_021953, NM_202002, NM_202003

CCDS: CCDS76506, CCDS8515, CCDS8516, CCDS8517

Canonical transcript exons

ENST00000359843 — 9 exons

Exon	Start	End
ENSE00000713204	2864320	2864495
ENSE00000802797	2873977	2874525
ENSE00002239307	2876920	2877174
ENSE00002316271	2857680	2859663
ENSE00003520001	2872096	2872247
ENSE00003550960	2868563	2868754
ENSE00003590365	2865355	2865399
ENSE00003619367	2864683	2864752
ENSE00003665493	2866393	2866521

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9325 / max 225.1369, expressed in 1461 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128977	13.6432	1344
128976	6.0490	1248
128975	0.2403	133

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.01	gold quality
ganglionic eminence	UBERON:0004023	94.41	gold quality
endometrium epithelium	UBERON:0004811	93.37	gold quality
embryo	UBERON:0000922	89.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.64	gold quality
sperm	CL:0000019	87.86	gold quality
mucosa of transverse colon	UBERON:0004991	87.40	gold quality
left testis	UBERON:0004533	86.10	gold quality
stromal cell of endometrium	CL:0002255	85.93	gold quality
right testis	UBERON:0004534	85.62	gold quality
male germ cell	CL:0000015	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.16	gold quality
testis	UBERON:0000473	84.75	gold quality
lower esophagus mucosa	UBERON:0035834	84.46	gold quality
rectum	UBERON:0001052	83.55	gold quality
esophagus mucosa	UBERON:0002469	81.82	gold quality
secondary oocyte	CL:0000655	81.77	gold quality
vermiform appendix	UBERON:0001154	78.07	gold quality
bone marrow cell	CL:0002092	77.10	gold quality
trabecular bone tissue	UBERON:0002483	75.85	gold quality
bone marrow	UBERON:0002371	75.78	gold quality
lymph node	UBERON:0000029	75.03	gold quality
adrenal tissue	UBERON:0018303	74.11	gold quality
transverse colon	UBERON:0001157	74.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.18	gold quality
skin of leg	UBERON:0001511	72.72	gold quality
skin of abdomen	UBERON:0001416	72.45	gold quality
caecum	UBERON:0001153	72.35	gold quality
spleen	UBERON:0002106	72.17	gold quality
small intestine	UBERON:0002108	72.04	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	95.44
E-MTAB-6678	yes	7.81
E-ANND-3	yes	4.08
E-MTAB-8271	no	522.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

121 targets.

Target	Regulation
ABCC2
ACP5	Repression
ADAM2
AFP	Unknown
ALAS2	Unknown
ALB	Unknown
ALDOB	Unknown
ALDOC	Activation
AMBP	Activation
AP1	Unknown
APOB	Activation
APOE	Unknown
AR	Activation
AURKB	Activation
BIRC5	Activation
BMI1	Activation
BRCA2	Unknown
BRIP1	Unknown
BTG2	Activation
BUB1B	Activation
C4BPB
CAT	Activation
CCNA2	Activation
CCNB1	Activation
CCND1	Unknown
CCND2	Unknown
CCNE1	Activation
CCNE2	Activation
CCR2	Activation
CDC25A	Unknown

JASPAR motifs

Motif	Name	Family
MA2469.1	FOXM1	FOX

JASPAR matrix evidence (PMIDs): PMID:20360045

Upstream regulators (CollecTRI, top): ATM, E2F1, E2F4, ESR1, ESR2, FLI1, FOXC1, FOXM1, FOXO3, GLI1, HIF1A, HSF1, KLF4, MYC, NFIC, NR1H2, NR1H3, NR1H4, NR1I3, PARP1, SP1, STAT3, TEAD1, TP53, TWIST1

miRNA regulators (miRDB)

66 targeting FOXM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3191-5P	99.24	66.52	1722

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• hepatocyte nuclear translocation of the FoxM1B transgene protein was rapidly induced during the hepatic acute phase response (PMID:14686788)
• Data show that forkhead box M1B (FoxM1B) transcriptional activity requires binding of Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins. (PMID:15024056)
• Expression of FoxM1 is significantly elevated in primary breast cancer and microarray analysis shows that FoxM1 regulates genes that are essential for faithful chromosome segregation and mitosis. (PMID:15958562)
• FoxM1 regulates transcription of cell cycle genes critical for progression into S-phase and mitosis. (PMID:16314512)
• Foxm1-depleted A549 cells exhibit reduced expression of cell cycle-promoting cyclin A2 and cyclin B1 genes. These data show that Foxm1 stimulates the proliferation of tumor cells during progression of NSCLC. (PMID:16489016)
• Cyclin-dependent kinases regulate the transcriptional activity of FOXM1c; a combination of three phosphorylation sites mediates the Cyclin E and Cyclin A/CDK2 effects. (PMID:16504183)
• FoxM1 regulates the expression of Skp2 protein, which is known to promote degradation of the cell cycle regulator p27; results showed that FoxM1 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity. (PMID:16585184)
• Increased expression of SHh mRNA in human colonic adenocarcinomas and in a colorectal cell line with downstream increased expression of FOXM1 mRNA known to promote cell proliferation. (PMID:16701100)
• FoxM1 and FoxO3a cooperate to regulate ERalpha gene transcription (PMID:16809346)
• cyclin D1/Cdk4 converts FOXM1c from an almost inactive form into a strong transactivator in G1-phase, i.e., just at the time point at which the transcriptional activity of FOXM1 is required for stimulation of the G1/S-transition (PMID:16913845)
• FOXM1 stimulates proliferation by promoting G1/S transition, as well as G2/M transition, and deregulation of such potent activators of proliferation can result in tumorigenesis. (PMID:16913846)
• Human FoxM1 nkockout mousse lungs demonstrated impaired cell proliferation in association with sustained expression of p27(Kip1) and decreased expression of cyclin B1 and Cdc25C. (PMID:16955137)
• interference with FoxM1 activity may contribute to the increase in mitotic errors seen in human diseases such as cancer and early onset of ageing diseases[review] (PMID:17014965)
• These results identify a novel role for FoxM1 in the transcriptional response during DNA damage/checkpoint signaling and show a novel mechanism by which Chk2 protein regulates expression of DNA repair enzymes. (PMID:17101782)
• Data show FoxM1 regulates growth factor-induced expression of kinase-interacting stathmin (KIS) to promote cell cycle progression. (PMID:17984092)
• FOXM1 regulates genes that control G1/S-transition, S-phase progression, G2/M-transition and M-phase progression–{REVIEW} (PMID:18020943)
• We found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. (PMID:18254960)
• FoxM1 is inactive in the G(1)/S transition through the action of the N-terminal autorepressor domain, while phosphorylation by cyclin A/cdk complexes in G(2) results in relief of inhibition by N terminus, activating FoxM1-mediated gene transcription. (PMID:18285455)
• Whereas FOXM1 expression is extinguished in terminally differentiated cells, it has been found to be upregulated and/or required in a number of different cancers [commentary] (PMID:18297053)
• TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers. (PMID:18393292)
• JNK1 is a critical transcriptional target of FoxM1 that contributes to FoxM1-regulated cell cycle progression, tumor cell migration, invasiveness, and anchorage-independent growth (PMID:18524773)
• FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase. (PMID:18573889)
• Cdh1-dependent degradation of FoxM1 is required to shut down transcriptional activation of mitotic regulators during exit from mitosis. (PMID:18758239)
• findings provide both clinical and mechanistic evidence that FoxM1 contributes to glioma progression by enhancing VEGF gene transcription and thus tumor angiogenesis (PMID:18974115)
• HIF-1alpha directly bound to the promoter of FoxM1 (PMID:19097132)
• FoxM1 expression was an independent poor prognostic factor in primary pulmonary squamous cell carcinoma (PMID:19121844)
• Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression. (PMID:19160488)
• increased expression of foxm1 is correlated with non-small cell lung cancer (PMID:19200615)
• FOXM1 is a cellular target and marker of gefitinib activity in breast cancer. (PMID:19276163)
• Given the importance of FoxM1b to regulation of the expression of genes key to cancer biology overall, dysregulated expression and activation of FoxM1b may play important roles in gastric cancer development and progression. (PMID:19351851)
• Data show that overexpression of FoxM1 partially protected cancer cells from the thiazole antibiotic-mediated cell death. (PMID:19440351)
• FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer. (PMID:19513552)
• FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for oral cavity squamous cell carcinoma treatment. (PMID:19525975)
• These data indicate that TIS21 is a novel target of SCF-Skp2 ubiquitin ligase, which is regulated by expression of FoxM1. (PMID:19615363)
• Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2alpha expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy (PMID:19672312)
• Induction of Foxm1 by oncogenic Ras requires reactive oxygen species (ROS). Elevated Foxm1, in turn, downregulates ROS levels by stimulating expression of ROS scavenger genes. (PMID:19696738)
• transcriptional activity of FoxM1 is controlled in a cell cycle-dependent fashion by temporally regulated phosphorylation and dephosphorylation events, and the phosphorylation at Ser-251 is critical for the activation of FoxM1 (PMID:19737929)
• Bcr-Abl represses the expression of RKIP, continuously activates pERK1/2, and suppresses FoxM1 expression, resulting in proliferation of CML cells. (PMID:20028985)
• A novel mechanism of acquired cisplatin resistance in breast cancer cells through the induction of FOXM1. (PMID:20068070)
• Down-regulation of FoxM1 inhibited cell proliferation, caused cell cycle arrest, and decreased invasion of human hepatocellular carcinoma MHCC-97H cells. (PMID:20154714)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxm1	ENSDARG00000003200
mus_musculus	Foxm1	ENSMUSG00000001517
rattus_norvegicus	Foxm1	ENSRNOG00000005936

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein M1 — Q08050 (reviewed: Q08050)

Alternative names: Forkhead-related protein FKHL16, Hepatocyte nuclear factor 3 forkhead homolog 11, M-phase phosphoprotein 2, MPM-2 reactive phosphoprotein 2, Transcription factor Trident, Winged-helix factor from INS-1 cells

All UniProt accessions (9): Q08050, A0A0D9SFF0, A0A2P9DTZ0, A0A2P9DTZ1, A0A2P9DTZ8, A8K591, H0YG99, H0YGS4, Q53Y49

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Also plays a role in DNA break repair, participating in the DNA damage checkpoint response. Promotes transcription of PHB2.

Subunit / interactions. Interacts with PINT87aa which is encoded by the circular form of the long non-coding RNA LINC-PINT; the interaction inhibits FOXM1-mediated transcription of PHB2.

Subcellular location. Nucleus.

Tissue specificity. Expressed in thymus, testis, small intestine, colon followed by ovary. Appears to be expressed only in adult organs containing proliferating/cycling cells or in response to growth factors. Also expressed in epithelial cell lines derived from tumors. Not expressed in resting cells. Isoform 2 is highly expressed in testis.

Post-translational modifications. Phosphorylated in M (mitotic) phase. Phosphorylation by the checkpoint kinase CHEK2 in response to DNA damage increases the FOXM1 protein stability probably stimulating the transcription of genes involved in DNA repair. Phosphorylated by CDK1 in late S and G2 phases, creating docking sites for the POLO box domains of PLK1. Subsequently, PLK1 binds and phosphorylates FOXM1, leading to activation of transcriptional activity and subsequent enhanced expression of key mitotic regulators. Phosphorylated by GSK3B leading to ubiquitination and proteasomal degradation. Ubiquitinated in a FBXW7-dependent manner leading to proteasomal degradation.

Domain organisation. Within the protein there is a domain which acts as a transcriptional activator. Insertion of a splicing sequence within it inactivates this transcriptional activity, as it is the case for isoform 4.

Induction. Induced during liver regeneration and oxidative stress.

Isoforms (3)

UniProt ID	Names	Canonical?
Q08050-1	1, FoxM1C, FOXM1-c	yes
Q08050-2	2, FoxM1B, FOXM1-b
Q08050-3	4, FoxM1A, FOXM1-a

RefSeq proteins (23): NP_001230017, NP_001230018, NP_001400854, NP_001400855, NP_001400856, NP_001400857, NP_001400858, NP_001400859, NP_001400860, NP_001400861, NP_001400862, NP_001400863, NP_001400864, NP_001400865, NP_001400866, NP_001400867, NP_001400868, NP_001400869, NP_001400870, NP_001400871, NP_068772, NP_973731, NP_973732 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR042839	FOXM1	Family
IPR047516	FH_FOXM1	Domain

Pfam: PF00250

UniProt features (49 total): modified residue 11, cross-link 6, compositionally biased region 5, sequence variant 5, mutagenesis site 5, region of interest 4, helix 4, strand 3, splice variant 2, chain 1, DNA-binding region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3G73	X-RAY DIFFRACTION	2.21
9XS1	X-RAY DIFFRACTION	2.5
7FJ2	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08050-F1	50.84	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (17): 331, 376, 489, 522, 611, 620, 627, 662, 693, 730, 739, 163, 201, 325, 356, 422, 440

Mutagenesis-validated functional residues (5):

Position	Phenotype
489	prevents phosphorylation by gsk3 and subsequent ubiquitination.
611	prevents phosphorylation by cdk1 and subsequent binding of polo box domains of plk1; when associated with a-693.
693	prevents phosphorylation by cdk1 and subsequent binding of polo box domains of plk1; when associated with a-611.
730	prevents phosphorylation by plk1 and impairs transcription activity; when associated with a-739.
739	prevents phosphorylation by plk1 and impairs transcription activity; when associated with a-730.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-156711	Polo-like kinase mediated events
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer

MSigDB gene sets: 577 (showing top): MORF_RAGE, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, RNGTGGGC_UNKNOWN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, MORF_FLT1, KANG_DOXORUBICIN_RESISTANCE_UP, MORF_ESPL1, GNF2_CENPF, MORF_BUB1, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, CROONQUIST_NRAS_SIGNALING_DN, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN

GO Biological Process (18): G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), DNA repair (GO:0006281), regulation of transcription by RNA polymerase II (GO:0006357), regulation of mitotic cell cycle (GO:0007346), positive regulation of cell population proliferation (GO:0008284), DNA damage response, signal transduction by p53 class mediator (GO:0030330), negative regulation of stress-activated MAPK cascade (GO:0032873), regulation of cell population proliferation (GO:0042127), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of Ras protein signal transduction (GO:0046578), regulation of cell cycle (GO:0051726), regulation of reactive oxygen species metabolic process (GO:2000377), positive regulation of double-strand break repair (GO:2000781), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein kinase binding (GO:0019901), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
G2/M Transition	2
Signaling by ALK fusions and activated point mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
DNA-templated transcription	3
mitotic cell cycle	2
cell population proliferation	2
regulation of cellular process	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
negative regulation of DNA-templated transcription	1
DNA metabolic process	1
DNA damage response	1
regulation of cell cycle	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
regulation of stress-activated MAPK cascade	1
negative regulation of MAPK cascade	1
stress-activated MAPK cascade	1
negative regulation of stress-activated protein kinase signaling cascade	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
Ras protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
cell cycle	1
regulation of metabolic process	1
reactive oxygen species metabolic process	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

4043 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXM1	CTNNB1	P35222	989
FOXM1	MYBL2	P10244	981
FOXM1	CCNA2	P20248	902
FOXM1	CDK1	P06493	896
FOXM1	ALKBH5	Q6P6C2	893
FOXM1	STAT3	P40763	892
FOXM1	SMAD3	P84022	876
FOXM1	MELK	Q14680	875
FOXM1	CCNB1	P14635	863
FOXM1	CENPF	P49454	845
FOXM1	PLK1	P53350	806
FOXM1	SNAI1	O95863	796
FOXM1	BIRC5	O15392	792
FOXM1	TP53	P04637	776
FOXM1	CCNL2	Q96S94	772

IntAct

72 interactions, top by confidence:

A	B	Type	Score
TCF7L2	CTNNB1	psi-mi:“MI:0914”(association)	0.970
FBXL2	SKP1	psi-mi:“MI:0914”(association)	0.900
FOXM1	CTNNB1	psi-mi:“MI:0915”(physical association)	0.670
CTNNB1	FOXM1	psi-mi:“MI:0407”(direct interaction)	0.670
FOXM1	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.670
CTNNB1	FOXM1	psi-mi:“MI:0403”(colocalization)	0.670
CTNNB1	FOXM1	psi-mi:“MI:0915”(physical association)	0.670
FOXM1	CTNNB1	psi-mi:“MI:0403”(colocalization)	0.670
FOXM1	TCF7L2	psi-mi:“MI:0915”(physical association)	0.610
BANP	FOXM1	psi-mi:“MI:0915”(physical association)	0.560
LINC-PINT	FOXM1	psi-mi:“MI:0915”(physical association)	0.560
LINC-PINT	FOXM1	psi-mi:“MI:0403”(colocalization)	0.560
CCNE1	FOXM1	psi-mi:“MI:0915”(physical association)	0.540
CCNE1	FOXM1	psi-mi:“MI:0217”(phosphorylation reaction)	0.540

BioGRID (226): FOXM1 (Affinity Capture-Western), FZR1 (Affinity Capture-Western), FOXM1 (Proximity Label-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YY25, A6NGG8, A6X8Z5, B2RQL2, B2RXH4, D3ZMK9, D3ZUE1, E9Q7F2, O08696, O14513, P59598, P97691, Q05860, Q05AH6, Q08050, Q0GGX2, Q0VET5, Q13029, Q2M1Z3, Q3U0P1, Q571I4, Q5PSV9, Q5SSG4, Q5U2M8, Q5VV67, Q63755, Q66H04, Q68DA7, Q69ZL1, Q6DIA7, Q6JPI3, Q6P1D7, Q6PAC4, Q6PG16, Q71F56, Q76N32, Q811R2, Q86YN6, Q86YV5, Q8BJS7

Diamond homologs: A0A2Z4LIS9, A0A8V0YY16, A3RK74, A3RK75, A4L7N3, A8MTJ6, A8MYZ6, A8XJN7, B3LYS5, B3P0K6, B4G4S8, B4HF64, B4JSC2, B4KBF6, B4MB78, B4NFR1, B4PTD3, B5RHS5, E1BPQ1, G3V7R4, O00409, O08696, O14270, O16850, O43524, O70220, O88470, P25364, P32027, P32031, P32315, P33205, P33206, P42128, P55316, P56260, P58012, P85037, P97691, P98177

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
CHEK2	up-regulates	FOXM1	phosphorylation
CDK4	up-regulates	FOXM1	phosphorylation
CDK1	up-regulates	FOXM1	phosphorylation
PLK1	up-regulates	FOXM1	phosphorylation
TEAD1	“up-regulates quantity by expression”	FOXM1	“transcriptional regulation”
CyclinB/CDK1	up-regulates	FOXM1	phosphorylation
FOXM1	“up-regulates quantity by expression”	SLC27A2
GSK3B	“down-regulates quantity by destabilization”	FOXM1	phosphorylation
SCF-FBW7	“down-regulates quantity by destabilization”	FOXM1	ubiquitination
USP5	“up-regulates quantity by stabilization”	FOXM1	deubiquitination
FOXM1	“up-regulates activity”	CTNNB1	binding
MELK	“up-regulates activity”	FOXM1	phosphorylation
HIPK2	“up-regulates activity”	FOXM1	phosphorylation
SRC	“up-regulates activity”	FOXM1	phosphorylation
CHEK1	“up-regulates activity”	FOXM1	phosphorylation
CDK2	“up-regulates activity”	FOXM1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

204 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	10
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

3922 predictions. Top by Δscore:

Variant	Effect	Δscore
12:2859662:ACC:A	acceptor_loss	1.0000
12:2859664:CTGAA:C	acceptor_loss	1.0000
12:2859665:T:C	acceptor_loss	1.0000
12:2864315:CCCA:C	donor_loss	1.0000
12:2864316:CCA:C	donor_loss	1.0000
12:2864317:CA:C	donor_loss	1.0000
12:2864319:C:CA	donor_loss	1.0000
12:2864494:CC:C	acceptor_gain	1.0000
12:2864495:CC:C	acceptor_gain	1.0000
12:2864495:CCTA:C	acceptor_loss	1.0000
12:2864496:C:CC	acceptor_gain	1.0000
12:2864496:CTA:C	acceptor_loss	1.0000
12:2864497:T:C	acceptor_loss	1.0000
12:2864757:T:TC	acceptor_gain	1.0000
12:2864763:C:CT	acceptor_gain	1.0000
12:2864764:A:T	acceptor_gain	1.0000
12:2864766:A:AC	acceptor_gain	1.0000
12:2864766:A:C	acceptor_gain	1.0000
12:2865417:T:TC	acceptor_gain	1.0000
12:2866517:GAGTT:G	acceptor_gain	1.0000
12:2866518:AGTT:A	acceptor_gain	1.0000
12:2866519:GTT:G	acceptor_gain	1.0000
12:2866520:TT:T	acceptor_gain	1.0000
12:2866521:TC:T	acceptor_loss	1.0000
12:2866522:C:CC	acceptor_gain	1.0000
12:2866523:T:G	acceptor_loss	1.0000
12:2868646:T:TA	donor_gain	1.0000
12:2868762:T:C	acceptor_gain	1.0000
12:2868762:T:TC	acceptor_gain	1.0000
12:2868764:A:C	acceptor_gain	1.0000

AlphaMissense

4960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:2866444:C:A	W308C	1.000
12:2866444:C:G	W308C	1.000
12:2866446:A:G	W308R	1.000
12:2866446:A:T	W308R	1.000
12:2866483:A:C	F295L	1.000
12:2866483:A:T	F295L	1.000
12:2866484:A:C	F295C	1.000
12:2866484:A:G	F295S	1.000
12:2866485:A:G	F295L	1.000
12:2866502:A:G	L289P	1.000
12:2866502:A:T	L289H	1.000
12:2866507:G:C	H287Q	1.000
12:2866507:G:T	H287Q	1.000
12:2866509:G:C	H287D	1.000
12:2866514:A:T	I285N	1.000
12:2866519:G:C	N283K	1.000
12:2866519:G:T	N283K	1.000
12:2868566:C:A	W281C	1.000
12:2868566:C:G	W281C	1.000
12:2868568:A:G	W281R	1.000
12:2868568:A:T	W281R	1.000
12:2868633:A:C	L259W	1.000
12:2868633:A:G	L259S	1.000
12:2868663:A:T	I249N	1.000
12:2868666:G:T	A248D	1.000
12:2868675:A:T	I245K	1.000
12:2866439:A:C	I310S	0.999
12:2866439:A:G	I310T	0.999
12:2866439:A:T	I310N	0.999
12:2866445:C:G	W308S	0.999

dbSNP variants (sampled 300 via entrez): RS1000087903 (12:2860557 G>T), RS1000266917 (12:2877271 C>A,T), RS1000319560 (12:2877170 G>C,T), RS1000449104 (12:2871406 G>C), RS1000517837 (12:2864523 C>A,G), RS1000589659 (12:2872449 A>C), RS1000735501 (12:2871041 C>T), RS1001153368 (12:2878167 G>A,T), RS1001252557 (12:2877466 C>G), RS1001714323 (12:2876503 G>A), RS1001786609 (12:2870555 C>T), RS1002051765 (12:2872913 G>A), RS1002205126 (12:2878806 T>C), RS1002228588 (12:2876814 G>A), RS1002298997 (12:2867106 T>A)

Disease associations

OMIM: gene MIM:602341 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002386_9	Cognitive function	8.000000e-06
GCST008839_308	Height	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4739852 (SINGLE PROTEIN), CHEMBL6177910 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,856 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL408	TROGLITAZONE	4	38,856

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

15 potent at pChembl≥5 of 28 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	Ki	11	nM	CHEMBL5089001
7.85	Ki	14	nM	CHEMBL5089499
7.67	Ki	21.46	nM	CHEMBL4740210
7.40	Ki	40	nM	CHEMBL5075226
7.29	Ki	51	nM	CHEMBL5075356
7.28	Ki	51.97	nM	TROGLITAZONE
7.19	Ki	65	nM	CHEMBL5081655
7.12	Ki	76	nM	CHEMBL5076752
7.00	Ki	100	nM	CHEMBL5089867
6.89	Ki	130	nM	CHEMBL5092745
6.84	Ki	143	nM	CHEMBL1597711
6.80	Kd	160	nM	CHEMBL5272715
6.72	Ki	190	nM	CHEMBL5081041
6.64	Ki	230	nM	CHEMBL5075586
6.04	Kd	910	nM	CHEMBL2205761

PubChem BioAssay actives

4 with measured affinity, of 32 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(5Z)-5-[[3-methoxy-4-[[4-(trifluoromethyl)phenoxy]methyl]phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1727628: Binding affinity to recombinant FOXM1 DBD (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as disruption of FOXM1-DNA complex preincubated for 1.5 hrs followed by DNA addition measured after 20 mins by EMSA	ki	0.0215	uM
5-[[4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione	1727628: Binding affinity to recombinant FOXM1 DBD (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as disruption of FOXM1-DNA complex preincubated for 1.5 hrs followed by DNA addition measured after 20 mins by EMSA	ki	0.0520	uM
N-[2-[2-[4-[(4-chlorophenyl)methoxy]phenoxy]ethoxy]ethyl]cyclohexanamine	1947132: Binding affinity to recombinant FOXM1 DBD (222 to 360 residues) (unknown origin) by SPR analysis	kd	0.1600	uM
(5-imino-4-phenyl-1,3,4-thiadiazol-2-yl)-thiophen-2-ylmethanone	1802509: Fluorescence-based Affinity Assay from Article 10.1016/j.bioorg.2016.11.003: “Rational identification of natural organic compounds to target the intermolecular interaction between Foxm and DNA in colorectal cancer.”	kd	3.8000	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, decreases expression, increases activity, increases response to substance, decreases reaction (+2 more)	6
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	4
(+)-JQ1 compound	decreases response to substance, decreases expression	4
Fulvestrant	affects cotreatment, increases methylation, decreases expression	4
bisphenol A	affects expression, affects cotreatment, increases methylation	2
cobaltous chloride	decreases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	2
palbociclib	decreases expression, decreases reaction, affects reaction, decreases activity	2
N-methyl-delta-3,3-dihydroindole-2,2 diketone	decreases reaction, increases expression, decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Arsenic	decreases methylation, increases abundance, affects cotreatment, decreases expression	2
Cadmium	decreases reaction, increases abundance, increases phosphorylation, decreases expression	2
Hydrogen Peroxide	decreases expression, affects expression	2
Quercetin	decreases expression, increases expression	2
Dronabinol	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases phosphorylation	2
tert-Butylhydroperoxide	decreases expression	2
FR900359	decreases phosphorylation	1
SirReal2	increases expression	1
mivebresib	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
diminazene aceturate	decreases expression	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases expression	1

ChEMBL screening assays

53 unique, capped per target: 53 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4733556	Binding	Binding affinity to recombinant FOXM1 DBD (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as disruption of FOXM1-DNA complex preincubated for 1.5 hrs followed by DNA addition measured after 20 mins by EMSA	SP1-independent inhibition of FOXM1 by modified thiazolidinediones. — Eur J Med Chem

Cellosaurus cell lines

18 cell lines: 9 transformed cell line, 6 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2B8	SEES3-1V human FOXM1, clone1	Embryonic stem cell	Male
CVCL_A2B9	SEES3-1V human FOXM1, clone2	Embryonic stem cell	Male
CVCL_A2C0	SEES3-1V human FOXM1, clone3	Embryonic stem cell	Male
CVCL_B8GG	Abcam HCT 116 FOXM1 KO	Cancer cell line	Male
CVCL_B8W2	Abcam MCF-7 FOXM1 KO	Cancer cell line	Female
CVCL_B9IQ	Abcam A-549 FOXM1 KO	Cancer cell line	Male
CVCL_D7Q5	Ubigene A-549 FOXM1 KO	Cancer cell line	Male
CVCL_DH25	SVpgC2a-FOXM1B	Transformed cell line	Female
CVCL_DH26	SVpgC2a-FOXM1B/SVFN1	Transformed cell line	Female
CVCL_DH27	SVpgC2a-FOXM1B/SVFN2	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.