Foxo4 forkhead box O4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Foxo4provided by MGI
Official Full Name: forkhead box O4provided by MGI
Primary source: MGI:MGI:1891915
See related: Ensembl:ENSMUSG00000042903 AllianceGenome:MGI:1891915
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: afx; Afxh; Mllt7
Summary: Enables sequence-specific DNA binding activity. Acts upstream of or within mitotic G2 DNA damage checkpoint signaling; negative regulation of cell population proliferation; and positive regulation of DNA-templated transcription. Predicted to be located in cytosol and nuclear speck. Predicted to be active in nucleus. Is expressed in several structures, including adipose tissue; central nervous system; early embryo; genitourinary system; and skeletal muscle. Orthologous to human FOXO4 (forkhead box O4). [provided by Alliance of Genome Resources, Jul 2025]
Expression: Broad expression in placenta adult (RPKM 68.4), limb E14.5 (RPKM 10.1) and 21 other tissues See more
Orthologs: all
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Try the new Transcripts and proteins table

Genomic context

Location:: X D; X 43.89 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	X	NC_000086.8 (100297855..100304479)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	X	NC_000086.7 (101254261..101260873)

Chromosome X - NC_000086.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice.
Title: FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice.
FOXO4 alleviates hippocampal neuronal damage in epileptic mice via the miR-138-5p/ROCK2 axis.
Title: FOXO4 alleviates hippocampal neuronal damage in epileptic mice via the miR-138-5p/ROCK2 axis.
FBXO7 triggers caspase 8-mediated proteolysis of the transcription factor FOXO4 and exacerbates neuronal cytotoxicity.
Title: FBXO7 triggers caspase 8-mediated proteolysis of the transcription factor FOXO4 and exacerbates neuronal cytotoxicity.
FOXO4 ameliorates alcohol-induced chronic liver injury via inhibiting NF-kappaB and modulating gut microbiota in C57BL/6J mice.
Title: FOXO4 ameliorates alcohol-induced chronic liver injury via inhibiting NF-κB and modulating gut microbiota in C57BL/6J mice.
Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.
Title: Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.
KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21.
Title: KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21.
FOXO proteins regulate apoptosis and cell cycle related proteins in mouse preimplantation embryos. Moreover, there might be an autofeedback mechanism where FOXO1, FOXO3, and FOXO4 regulate SIRT1 protein expression
Title: FoxO transcription factors 1 regulate mouse preimplantation embryo development.
These findings suggest that WNK1 is involved in the physiological regulation of mammalian skeletal muscle hypertrophy and atrophy via interactions with FOXO4.
Title: WNK1 regulates skeletal muscle cell hypertrophy by modulating the nuclear localization and transcriptional activity of FOXO4.
FOXO transcription factors play a salutary role in the protection against the diet-induced fatty liver disease.
Title: FOXO transcription factors protect against the diet-induced fatty liver disease.
FoxOs exacerbate the loss of cancellous bone mass associated with type 1 diabetes.
Title: Deletion of FoxO1, 3, and 4 in Osteoblast Progenitors Attenuates the Loss of Cancellous Bone Mass in a Mouse Model of Type 1 Diabetes.

Submit: New GeneRIF Correction See all GeneRIFs (42)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Gene trapped (1)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables beta-catenin binding	IEA Inferred from Electronic Annotation more info
enables beta-catenin binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables nucleic acid binding	ISO Inferred from Sequence Orthology more info
enables promoter-specific chromatin binding	IEA Inferred from Electronic Annotation more info
enables promoter-specific chromatin binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within mitotic G2 DNA damage checkpoint signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of G0 to G1 transition	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of G0 to G1 transition	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of G0 to G1 transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of smooth muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smooth muscle cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein K48-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in response to water-immersion restraint stress	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in nuclear speck	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: forkhead box protein O4

Names: fork head domain transcription factor AFX1; forkhead protein; myeloid/lymphoid or mixed lineage-leukemia translocation to 7 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_018789.2 → NP_061259.1 forkhead box protein O4

See identical proteins and their annotated locations for NP_061259.1

Status: VALIDATED

Source sequence(s)

AL671926

Consensus CDS

CCDS41077.1

UniProtKB/Swiss-Prot

Q9WVH3

UniProtKB/TrEMBL

B1AUT2, B1AUT3

Related

ENSMUSP00000059420.5, ENSMUST00000062000.6

Conserved Domains (4) summary

pfam05887
Location:6 → 83

Trypan_PARP; Procyclic acidic repetitive protein (PARP)

cd00059
Location:101 → 181

FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...

pfam16675
Location:359 → 399

FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2

pfam16676
Location:466 → 503

FOXO-TAD; Transactivation domain of FOXO protein family

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000086.8 Reference GRCm39 C57BL/6J

Range

100297855..100304479

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006528139.3 → XP_006528202.1 forkhead box protein O4 isoform X1

See identical proteins and their annotated locations for XP_006528202.1

UniProtKB/TrEMBL

Q3TZJ4, Q4KL34

Conserved Domains (2) summary

PHA03247
Location:18 → 130

PHA03247; large tegument protein UL36; Provisional

cl00061
Location:101 → 151

FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...