FOXO4 forkhead box O4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FOXO4provided by HGNC
Official Full Name: forkhead box O4provided by HGNC
Primary source: HGNC:HGNC:7139
See related: Ensembl:ENSG00000184481 MIM:300033; AllianceGenome:HGNC:7139
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AFX; AFX1; MLLT7
Summary: This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
Expression: Broad expression in placenta (RPKM 74.9), testis (RPKM 15.0) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq13.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (71095851..71103532)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (69529947..69537628)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (70315701..70323382)

Chromosome X - NC_000023.11 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.
Title: Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.
The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.
Title: The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.
Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.
Title: Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.
Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.
Title: Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.
Multiple regulatory intrinsically disordered motifs control FOXO4 transcription factor binding and function.
Title: Multiple regulatory intrinsically disordered motifs control FOXO4 transcription factor binding and function.
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.
Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective.
Title: Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective.
Clinicopathological Significance of FOXO4 Expression and Correlation with Prx1 in Head and Neck Squamous Cell Carcinoma.
Title: Clinicopathological Significance of FOXO4 Expression and Correlation with Prx1 in Head and Neck Squamous Cell Carcinoma.
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.
lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes.
Title: lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes.

Submit: New GeneRIF Correction See all GeneRIFs (95)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables beta-catenin binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nucleic acid binding	EXP Inferred from Experiment more info	PubMed
enables promoter-specific chromatin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in mitotic G2 DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of G0 to G1 transition	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smooth muscle cell differentiation	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 transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in response to water-immersion restraint stress	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in nuclear speck	IDA Inferred from Direct Assay 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	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: forkhead box protein O4

Names: fork head domain transcription factor AFX1; myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7

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.

Genomic

NG_016418.1 RefSeqGene

Range

4703..12384

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001170931.2 → NP_001164402.1 forkhead box protein O4 isoform 2

See identical proteins and their annotated locations for NP_001164402.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 2 also known as isoform zeta) compared to isoform 1.

Source sequence(s)

AF384029, AL590764, AW292413

Consensus CDS

CCDS55440.1

UniProtKB/Swiss-Prot

P98177

Related

ENSP00000342209.3, ENST00000341558.3

Conserved Domains (3) summary

cd00059
Location:58 → 126

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:303 → 340

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

pfam16676
Location:410 → 448

FOXO-TAD; Transactivation domain of FOXO protein family
NM_005938.4 → NP_005929.2 forkhead box protein O4 isoform 1

See identical proteins and their annotated locations for NP_005929.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1 also known as AFX alpha).

Source sequence(s)

AL590764, AW292413, BC106761

Consensus CDS

CCDS43969.1

UniProtKB/Swiss-Prot

B7WPJ7, O43821, P98177, Q13720, Q3KPF1, Q8TDK9

Related

ENSP00000363377.3, ENST00000374259.8

Conserved Domains (4) summary

pfam05887
Location:4 → 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:358 → 395

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

pfam16676
Location:465 → 503

FOXO-TAD; Transactivation domain of FOXO protein family