This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with... See more...

Aliases for FOXE1 Gene

Aliases for FOXE1 Gene

  • Forkhead Box E1 2 3 5
  • Thyroid Transcription Factor 2 2 3 4
  • HFKH4 2 3 4
  • TTF-2 2 3 4
  • Forkhead-Related Protein FKHL15 3 4
  • HNF-3/Fork Head-Like Protein 5 3 4
  • Forkhead Box Protein E1 3 4
  • Forkhead Box Protein E2 3 4
  • FKHL15 3 4
  • FOXE2 3 4
  • HFKL5 3 4
  • TITF2 3 4
  • TTF2 3 4
  • Forkhead Box E1 (Thyroid Transcription Factor 2) 2
  • Forkhead, Drosophila, Homolog-Like 15 3
  • Forkhead Box E2 2
  • NMTC4 3
  • FOXE1 5

External Ids for FOXE1 Gene

Previous HGNC Symbols for FOXE1 Gene

  • FKHL15
  • TITF2
  • FOXE2

Previous GeneCards Identifiers for FOXE1 Gene

  • GC09P091440
  • GC09P092359
  • GC09P094072
  • GC09P095995
  • GC09P097695
  • GC09P099655
  • GC09P100615
  • GC09P070216

Summaries for FOXE1 Gene

Entrez Gene Summary for FOXE1 Gene

  • This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with susceptibility to nonmedullary thyroid cancer-4. [provided by RefSeq, Nov 2016]

GeneCards Summary for FOXE1 Gene

FOXE1 (Forkhead Box E1) is a Protein Coding gene. Diseases associated with FOXE1 include Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate and Thyroid Cancer, Nonmedullary, 4. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and DNA-binding transcription factor activity, RNA polymerase II-specific. An important paralog of this gene is FOXE3.

UniProtKB/Swiss-Prot Summary for FOXE1 Gene

  • Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression.

Gene Wiki entry for FOXE1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FOXE1 Gene

Genomics for FOXE1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FOXE1 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
GH09J097855 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 276.8 +0.6 575 2 ZNF600 ZNF10 CTCF YY1 SPI1 ZNF189 CBX8 POLR2A GLIS1 ZNF202 FOXE1 HSALNG0073144 PTCSC2 ZNF782 NCBP1 PTMAP11 TSTD2 MFSD14C ZNF322P1 TRMO
GH09J097852 Enhancer 0.3 ENCODE 250.7 -1.1 -1062 0.1 EZH2 FOXE1 HSALNG0073144 PTCSC2 HSALNG0073148 XPA lnc-FOXE1-2
GH09J097853 Enhancer 0.3 ENCODE 250.7 -0.7 -692 0 EZH2 FOXE1 HSALNG0073144 PTCSC2 HSALNG0073148 lnc-FOXE1-2 XPA
GH09J097873 Enhancer 1.4 VISTA Ensembl ENCODE 32.9 +22.7 22679 4.6 ZNF600 JUND ATF2 CEBPA ZNF10 ZIC2 CEBPB DEK BHLHE40 MAX HSALNG0073152 FOXE1 TRMO lnc-TRMO-2
GH09J097801 Promoter/Enhancer 1.6 FANTOM5 ENCODE CraniofacialAtlas 20.8 -50.2 -50172 2.4 IKZF1 JUND ATF2 CEBPA BRCA1 NFIC ZIC2 ZBTB10 NONO CTCF PTCSC2-001 FOXE1 NUTM2G CORO2A HSALNG0073143 PTCSC2 lnc-FOXE1-2 XPA
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FOXE1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FOXE1

Top Transcription factor binding sites by QIAGEN in the FOXE1 gene promoter:
  • FOXO1
  • FOXO1a
  • FOXO4
  • GR
  • GR-alpha
  • Nkx6-1
  • NRSF form 1
  • NRSF form 2
  • p53
  • Pax-4a

Genomic Locations for FOXE1 Gene

Latest Assembly
chr9:97,853,226-97,856,717
(GRCh38/hg38)
Size:
3,492 bases
Orientation:
Plus strand

Previous Assembly
chr9:100,615,508-100,618,999
(GRCh37/hg19 by Entrez Gene)
Size:
3,492 bases
Orientation:
Plus strand

chr9:100,615,536-100,618,986
(GRCh37/hg19 by Ensembl)
Size:
3,451 bases
Orientation:
Plus strand

Genomic View for FOXE1 Gene

Genes around FOXE1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXE1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXE1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FOXE1 Gene

Proteins for FOXE1 Gene

  • Protein details for FOXE1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00358-FOXE1_HUMAN
    Recommended name:
    Forkhead box protein E1
    Protein Accession:
    O00358
    Secondary Accessions:
    • O75765
    • Q5T109
    • Q99526

    Protein attributes for FOXE1 Gene

    Size:
    373 amino acids
    Molecular mass:
    38076 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=CAA64246.1; Type=Miscellaneous discrepancy; Note=Several conflicts.; Evidence={ECO:0000305};

neXtProt entry for FOXE1 Gene

Post-translational modifications for FOXE1 Gene

Other Protein References for FOXE1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FOXE1 Gene

Domains & Families for FOXE1 Gene

Gene Families for FOXE1 Gene

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

Suggested Antigen Peptide Sequences for FOXE1 Gene

GenScript: Design optimal peptide antigens:
  • Thyroid transcription factor 2 (FOXE1_HUMAN)
genes like me logo Genes that share domains with FOXE1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FOXE1 Gene

Function for FOXE1 Gene

Molecular function for FOXE1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression.
GENATLAS Biochemistry:
transcription factor-like 15,with a Drosophila homeo forkhead DNA binding domain homolog,expressed in the developing thyroid,in most of the foregut endoderm,including Rathke pouch

Phenotypes From GWAS Catalog for FOXE1 Gene

Gene Ontology (GO) - Molecular Function for FOXE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IMP,ISA --
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IDA 9697705
GO:0005515 protein binding IPI 27852061
genes like me logo Genes that share ontologies with FOXE1: view
genes like me logo Genes that share phenotypes with FOXE1: view

Human Phenotype Ontology for FOXE1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FOXE1 Gene

MGI Knock Outs for FOXE1:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXE1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for FOXE1 Gene

Localization for FOXE1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXE1 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 FOXE1 gene
Compartment Confidence
nucleus 5
extracellular 2
cytosol 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for FOXE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA,IDA 9697705
genes like me logo Genes that share ontologies with FOXE1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for FOXE1 Gene

Pathways & Interactions for FOXE1 Gene

PathCards logo

SuperPathways for FOXE1 Gene

No Data Available

SIGNOR curated interactions for FOXE1 Gene

Activates:

Gene Ontology (GO) - Biological Process for FOXE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,NAS 9169137
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IMP 12165566
GO:0006590 thyroid hormone generation IEA,ISS --
GO:0009653 anatomical structure morphogenesis NAS 9169137
genes like me logo Genes that share ontologies with FOXE1: view

No data available for Pathways by source for FOXE1 Gene

Drugs & Compounds for FOXE1 Gene

(2) Drugs for FOXE1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for FOXE1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FOXE1: view

Transcripts for FOXE1 Gene

mRNA/cDNA for FOXE1 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXE1

Alternative Splicing Database (ASD) splice patterns (SP) for FOXE1 Gene

No ASD Table

Relevant External Links for FOXE1 Gene

GeneLoc Exon Structure for
FOXE1

Expression for FOXE1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FOXE1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FOXE1 Gene

This gene is overexpressed in Thyroid (x43.1).

Protein differential expression in normal tissues from HIPED for FOXE1 Gene

This gene is overexpressed in Monocytes (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FOXE1 Gene



Protein tissue co-expression partners for FOXE1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FOXE1

SOURCE GeneReport for Unigene cluster for FOXE1 Gene:

Hs.159234

mRNA Expression by UniProt/SwissProt for FOXE1 Gene:

O00358-FOXE1_HUMAN
Tissue specificity: Detected in adult brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, heart, colon, small intestine testis and thymus. Expression was strongest in heart and pancreas.

Evidence on tissue expression from TISSUES for FOXE1 Gene

  • Nervous system(4.3)
  • Skin(4.3)
  • Thyroid gland(3.6)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FOXE1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • chin
  • ear
  • epiglottis
  • eye
  • face
  • head
  • hypothalamus
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • parathyroid
  • pharynx
  • pituitary gland
  • skull
  • thyroid
Thorax:
  • heart
  • lung
Abdomen:
  • intestine
  • large intestine
  • small intestine
Pelvis:
  • placenta
  • uterus
General:
  • blood
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with FOXE1: view

Primer products for research

Orthologs for FOXE1 Gene

This gene was present in the common ancestor of animals.

Orthologs for FOXE1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FOXE1 30
  • 99 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia FOXE1 29 30
  • 87.42 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Foxe1 29 16 30
  • 86.65 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Foxe1 29
  • 85.2 (n)
Oppossum
(Monodelphis domestica)
Mammalia FOXE1 30
  • 64 (a)
OneToOne
Chicken
(Gallus gallus)
Aves FOXE1 29 30
  • 70.14 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia foxe1 29
  • 59.05 (n)
Zebrafish
(Danio rerio)
Actinopterygii foxe1 29 30
  • 61.97 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta fd64A 31
  • 63 (a)
fd96Cb 31
  • 41 (a)
Worm
(Caenorhabditis elegans)
Secernentea unc-130 31
  • 49 (a)
pha-4 30
  • 16 (a)
ManyToMany
Species where no ortholog for FOXE1 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)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Dog (Canis familiaris)
  • 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)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • 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 Squirt (Ciona savignyi)
  • 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)

Evolution for FOXE1 Gene

ENSEMBL:
Gene Tree for FOXE1 (if available)
TreeFam:
Gene Tree for FOXE1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FOXE1: view image
Alliance of Genome Resources:
Additional Orthologs for FOXE1

Paralogs for FOXE1 Gene

(14) SIMAP similar genes for FOXE1 Gene using alignment to 1 proteins:

  • FOXE1_HUMAN
genes like me logo Genes that share paralogs with FOXE1: view

Variants for FOXE1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for FOXE1 Gene

FOXE1_HUMAN-O00358
An alanine stretch that varies from 12 to 19 residues is present. This polymorphisms can be used as a marker to study the role of FOXE1 in other cases of thyroid dysgenesis, especially in familial cases.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FOXE1 Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
1028765 Uncertain Significance: Bamforth-Lazarus syndrome 97,854,780(+) C/G
NM_004473.4(FOXE1):c.866C>G (p.Pro289Arg)
MISSENSE
1031429 Uncertain Significance: Bamforth-Lazarus syndrome 97,855,001(+) C/G
NM_004473.4(FOXE1):c.1087C>G (p.Pro363Ala)
MISSENSE
997656 Uncertain Significance: Bamforth-Lazarus syndrome 97,854,447(+) C/T
NM_004473.4(FOXE1):c.533C>T (p.Ala178Val)
MISSENSE
rs104894110 Pathogenic: Bamforth-Lazarus syndrome. Bamforth-Lazarus syndrome (BLS) [MIM:241850] 97,854,108(+) C/Tp.Ala65Val
NM_004473.4(FOXE1):c.194C>T (p.Ala65Val)
MISSENSE
rs104894111 Pathogenic: Hypothyroidism, thyroidal, with spiky hair and cleft palate 97,854,218(+) C/Tp.Arg102Cys
NM_004473.4(FOXE1):c.304C>T (p.Arg102Cys)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for FOXE1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for FOXE1 Gene

Variant ID Type Subtype PubMed ID
nsv6627 CNV deletion 18451855
nsv825000 CNV gain 20364138
nsv950914 CNV deletion 24416366

Variation tolerance for FOXE1 Gene

Gene Damage Index Score: 1.93; 35.83% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FOXE1 Gene

Human Gene Mutation Database (HGMD)
FOXE1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FOXE1
Leiden Open Variation Database (LOVD)
FOXE1

SNP Genotyping and Copy Number Assays for research

Disorders for FOXE1 Gene

MalaCards: The human disease database

(33) MalaCards diseases for FOXE1 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search FOXE1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FOXE1_HUMAN
  • Bamforth-Lazarus syndrome (BLS) [MIM:241850]: A disease characterized by thyroid agenesis, cleft palate and choanal atresia. {ECO:0000269 PubMed:12165566, ECO:0000269 PubMed:21177256, ECO:0000269 PubMed:24219130, ECO:0000269 PubMed:9697705}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Thyroid cancer, non-medullary, 4 (NMTC4) [MIM:616534]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269 PubMed:25381600}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Additional Disease Information for FOXE1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with FOXE1: view

No data available for Genatlas for FOXE1 Gene

Publications for FOXE1 Gene

  1. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. (PMID: 9697705) Clifton-Bligh RJ … Chatterjee VK (Nature genetics 1998) 2 3 4 22 72
  2. A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis. (PMID: 16882747) Baris I … Battaloglu E (The Journal of clinical endocrinology and metabolism 2006) 3 4 22 72
  3. A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. (PMID: 12165566) Castanet M … Polak M (Human molecular genetics 2002) 3 4 22 72
  4. Identification of a novel germline FOXE1 variant in patients with familial non-medullary thyroid carcinoma (FNMTC). (PMID: 25381600) Pereira JS … Cavaco BM (Endocrine 2015) 3 4 72
  5. MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1. (PMID: 21177256) Venza I … Venza M (Human molecular genetics 2011) 3 4 72

Products for FOXE1 Gene

Sources for FOXE1 Gene