Members of the winged-helix/forkhead family of transcription factors, such as FOXN4, are characterized by a 110-amino acid DNA-binding domain that can fold into a variant of the helix-turn-helix motif consisting of 3 alpha helices flanked by 2 large loops or wings. These transcription factors are involved in a variety of biologic processes as key regulators in development and m... See more...

Aliases for FOXN4 Gene

Aliases for FOXN4 Gene

  • Forkhead Box N4 2 3 5
  • Forkhead Box Protein N4 3 4
  • Forkhead/Winged Helix Transcription Factor FOXN4 3
  • FOXN4 5

External Ids for FOXN4 Gene

Previous GeneCards Identifiers for FOXN4 Gene

  • GC12M108775
  • GC12M109554
  • GC12M108180
  • GC12M108178
  • GC12M109715
  • GC12M106733

Summaries for FOXN4 Gene

Entrez Gene Summary for FOXN4 Gene

  • Members of the winged-helix/forkhead family of transcription factors, such as FOXN4, are characterized by a 110-amino acid DNA-binding domain that can fold into a variant of the helix-turn-helix motif consisting of 3 alpha helices flanked by 2 large loops or wings. These transcription factors are involved in a variety of biologic processes as key regulators in development and metabolism (Li et al., 2004 [PubMed 15363391]).[supplied by OMIM, Mar 2008]

GeneCards Summary for FOXN4 Gene

FOXN4 (Forkhead Box N4) is a Protein Coding gene. Diseases associated with FOXN4 include Lymphedema-Distichiasis Syndrome. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is FOXN3.

UniProtKB/Swiss-Prot Summary for FOXN4 Gene

  • Transcription factor essential for neural and some non-neural tissues development, such as retina and lung respectively. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4-NOTCH signaling. Also acts synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and drive commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development (By similarity).

Additional gene information for FOXN4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FOXN4 Gene

Genomics for FOXN4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FOXN4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J109309 Promoter 1.7 EPDnew Ensembl CraniofacialAtlas 600.7 -0.3 -295 1.4 PRDM10 ZNF629 ZNF692 ZIC2 PATZ1 EZH2 REST ZNF501 ZNF341 ZNF561 FOXN4 SART3 TCHP UBE3B HSALNG0093882 MYO1H
GH12J109308 Promoter 0.7 Ensembl 600.7 +0.7 705 0.2 RNF2 EZH2 ZBTB20 BMI1 ZBTB48 CBX2 ZFHX2 EGR2 CBX8 FOXN4 piR-37790 ACACB
GH12J109347 Enhancer 0.8 FANTOM5 ENCODE 15.9 -38.6 -38597 1.1 PKNOX1 CTCF ZSCAN29 NCOR1 STAT5A TAL1 DPF2 TCF12 MEIS2 TEAD4 MYO1H FOXN4 LINC01486 KCTD10
GH12J109379 Enhancer 0.4 Ensembl 24.5 -67.9 -67895 0.2 MNT USF1 SP1 USF2 FOXN4 piR-48759-068 piR-38351-114 MYO1H KCTD10
GH12J108726 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 4.4 +578.3 578301 9.3 SP1 CREB1 GATAD2A CTCF HNRNPL ATF7 TEAD4 PRDM10 REST ZNF629 CORO1C RNU7-169P SSH1 LOC101929162 SELPLG PRDM4 ENSG00000257221 ACACB FOXN4 LOC105369969
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FOXN4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FOXN4

Top Transcription factor binding sites by QIAGEN in the FOXN4 gene promoter:
  • AML1a
  • FOXO1
  • FOXO1a
  • FOXO4
  • Ik-3

Genomic Locations for FOXN4 Gene

Genomic Locations for FOXN4 Gene
chr12:109,277,978-109,309,406
(GRCh38/hg38)
Size:
31,429 bases
Orientation:
Minus strand
chr12:109,715,783-109,747,025
(GRCh37/hg19)
Size:
31,243 bases
Orientation:
Minus strand

Genomic View for FOXN4 Gene

Genes around FOXN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FOXN4 Gene

Proteins for FOXN4 Gene

  • Protein details for FOXN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96NZ1-FOXN4_HUMAN
    Recommended name:
    Forkhead box protein N4
    Protein Accession:
    Q96NZ1
    Secondary Accessions:
    • Q6ZMR4
    • Q96NZ0

    Protein attributes for FOXN4 Gene

    Size:
    517 amino acids
    Molecular mass:
    55215 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for FOXN4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXN4 Gene

Post-translational modifications for FOXN4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FOXN4 Gene

No data available for DME Specific Peptides for FOXN4 Gene

Domains & Families for FOXN4 Gene

Gene Families for FOXN4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for FOXN4 Gene

Suggested Antigen Peptide Sequences for FOXN4 Gene

GenScript: Design optimal peptide antigens:
  • FOXN4 protein (A4FUA3_HUMAN)
  • FOXN4 protein (A6H901_HUMAN)
  • Forkhead box protein N4 (FOXN4_HUMAN)
genes like me logo Genes that share domains with FOXN4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FOXN4 Gene

Function for FOXN4 Gene

Molecular function for FOXN4 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor essential for neural and some non-neural tissues development, such as retina and lung respectively. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4-NOTCH signaling. Also acts synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and drive commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development (By similarity).

Phenotypes From GWAS Catalog for FOXN4 Gene

Gene Ontology (GO) - Molecular Function for FOXN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0000987 proximal promoter sequence-specific DNA binding IEA,ISS --
GO:0003677 DNA binding IEA --
GO:0003682 chromatin binding IEA,ISS 22323600
GO:0003700 DNA-binding transcription factor activity ISS --
genes like me logo Genes that share ontologies with FOXN4: view
genes like me logo Genes that share phenotypes with FOXN4: view

Animal Models for FOXN4 Gene

MGI Knock Outs for FOXN4:

Animal Model Products

CRISPR Products

miRNA for FOXN4 Gene

miRTarBase miRNAs that target FOXN4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXN4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FOXN4 Gene

Localization for FOXN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXN4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FOXN4 gene
Compartment Confidence
nucleus 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Mitochondria (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FOXN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus ISS --
genes like me logo Genes that share ontologies with FOXN4: view

Pathways & Interactions for FOXN4 Gene

PathCards logo

SuperPathways for FOXN4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for FOXN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001947 heart looping ISS --
GO:0006355 regulation of transcription, DNA-templated ISS --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0007275 multicellular organism development IEA --
GO:0007399 nervous system development IEA --
genes like me logo Genes that share ontologies with FOXN4: view

No data available for Pathways by source and SIGNOR curated interactions for FOXN4 Gene

Drugs & Compounds for FOXN4 Gene

No Compound Related Data Available

Transcripts for FOXN4 Gene

mRNA/cDNA for FOXN4 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXN4

Alternative Splicing Database (ASD) splice patterns (SP) for FOXN4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11
SP1: -
SP2: - -
SP3:
SP4: - - -

Relevant External Links for FOXN4 Gene

GeneLoc Exon Structure for
FOXN4

Expression for FOXN4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FOXN4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FOXN4 Gene

This gene is overexpressed in Testis (x29.6) and Cervix - Ectocervix (x4.2).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FOXN4

SOURCE GeneReport for Unigene cluster for FOXN4 Gene:

Hs.528316

Evidence on tissue expression from TISSUES for FOXN4 Gene

  • Nervous system(4.5)
  • Eye(2.3)
genes like me logo Genes that share expression patterns with FOXN4: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for FOXN4 Gene

Orthologs for FOXN4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for FOXN4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FOXN4 30 31
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia FOXN4 30 31
  • 88.85 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia FOXN4 30 31
  • 88.78 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Foxn4 30
  • 82.31 (n)
Mouse
(Mus musculus)
Mammalia Foxn4 30 17 31
  • 81.3 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia FOXN4 31
  • 57 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 12 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves FOXN4 30 31
  • 71.36 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia FOXN4 31
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia foxn4 30
  • 65.14 (n)
Zebrafish
(Danio rerio)
Actinopterygii foxn4 30 31
  • 63.51 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta jumu 31
  • 19 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FHL1 31
  • 9 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 72 (a)
OneToMany
Species where no ortholog for FOXN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for FOXN4 Gene

ENSEMBL:
Gene Tree for FOXN4 (if available)
TreeFam:
Gene Tree for FOXN4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FOXN4: view image

Paralogs for FOXN4 Gene

Paralogs for FOXN4 Gene

(14) SIMAP similar genes for FOXN4 Gene using alignment to 4 proteins:

  • FOXN4_HUMAN
  • A4FUA3_HUMAN
  • A6H901_HUMAN
  • S4R3U5_HUMAN
genes like me logo Genes that share paralogs with FOXN4: view

Variants for FOXN4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FOXN4 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs11609341 - p.Pro137Leu

Additional dbSNP identifiers (rs#s) for FOXN4 Gene

Structural Variations from Database of Genomic Variants (DGV) for FOXN4 Gene

Variant ID Type Subtype PubMed ID
nsv1070126 CNV deletion 25765185
nsv1136154 CNV deletion 24896259

Variation tolerance for FOXN4 Gene

Residual Variation Intolerance Score: 74% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.74; 46.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FOXN4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FOXN4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FOXN4 Gene

Disorders for FOXN4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for FOXN4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
lymphedema-distichiasis syndrome
  • lphdst
- elite association - COSMIC cancer census association via MalaCards
Search FOXN4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with FOXN4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FOXN4 Gene

Publications for FOXN4 Gene

  1. The finished DNA sequence of human chromosome 12. (PMID: 16541075) Scherer SE … Baylor College of Medicine Human Genome Sequencing Center Sequence Production Team (Nature 2006) 3 4
  2. Expression of the winged helix/forkhead gene, foxn4, during zebrafish development. (PMID: 15464224) Danilova N … Steiner LA (Brain research. Developmental brain research 2004) 3 4
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  4. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  5. Identification of FOXN4 as a tumor suppressor of breast carcinogenesis via the activation of TP53 and deactivation of Notch signaling. (PMID: 31430519) Wang X … Chen Z (Gene 2020) 3

Products for FOXN4 Gene

Sources for FOXN4 Gene