FOXM1

protein-coding

forkhead box M1, the group of Forkhead boxes

Gene summary

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. [provided by RefSeq, Jul 2011]

Previous symbols:

FKHL16

MANE transcript

NM_021953.4

Inheritance

—

ClinVar variants

U:112B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr12:2,857,680-2,877,174

External References & Databases

Ensembl (ENSG00000111206)

Transcript & Mutation Effects

hg38 • Region Span ~19.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FOXM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021953.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	2 clinvar	4 clinvar	8
missense			107 clinvar	7 clinvar	4 clinvar	118
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	112	9	8	129

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021953.4	RefSeq	NP_068772.2	8	MANE Select
ENST00000359843.8	Ensembl	ENSP00000352901.4	8	MANE Select
NM_001243088.2	RefSeq	NP_001230017.1	7	Standard
NM_001243089.2	RefSeq	NP_001230018.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
foxm1	Danio rerio	Structure: blood cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

foxm1

Danio rerio

Structure: blood cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cellular senescence - Homo sapiens (human)
EMT transition in Colorectal Cancer
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Polo-like kinase mediated events
Cyclin A/B1/B2 associated events during G2/M transition

Biological Process

G2/M transition of mitotic cell cycle
negative regulation of transcription by RNA polymerase II
DNA repair
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
positive regulation of cell population proliferation

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
protein binding
protein kinase binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342628
Coding exons: 9
Length: 19360
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.706	407	449	0.906	0.0000259	5187
Missense (PolyPhen)		107	132.91	0.80503		1610
Synonymous	-0.392	188	181	1.04	0.0000105	1658
Loss of Function	3.30	11	30.8	0.357	0.00000182	348

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Plays also a role in DNA breaks repair participating in the DNA damage checkpoint response. {ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:20360045}.;

Recessive Scores

pRec: 0.642

Intolerance Scores

LoFtool: 0.0154
RVIS EVS: 0.36
RVIS percentile EVS: 74.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium