This gene encodes a member of a subfamily of basic helix-loop-helix transcription repressors that have homology to the Drosophila enhancer of split genes. Members of this gene family regulate cell differentiation in numerous cell types. The protein encoded by this gene functions as a cofactor, interacting with other transcription factors through a tetrapeptide domain in its C-t... See more...

Aliases for HES6 Gene

Aliases for HES6 Gene

  • Hes Family BHLH Transcription Factor 6 2 3 5
  • BHLHb41 2 3 4
  • Class B Basic Helix-Loop-Helix Protein 41 3 4
  • Hairy And Enhancer Of Split 6 3 4
  • Transcription Cofactor HES-6 3 4
  • C-HAIRY1 3 4
  • Hairy And Enhancer Of Split 6 (Drosophila) 2
  • BHLHc23 3
  • BHLHB41 4
  • HES-6 3
  • HES6 5

External Ids for HES6 Gene

Previous GeneCards Identifiers for HES6 Gene

  • GC02M237195
  • GC02M237828
  • GC02M239163
  • GC02M239433
  • GC02M238928
  • GC02M238812
  • GC02M230937
  • GC02M239166
  • GC02M239172
  • GC02M239187
  • GC02M239205

Summaries for HES6 Gene

Entrez Gene Summary for HES6 Gene

  • This gene encodes a member of a subfamily of basic helix-loop-helix transcription repressors that have homology to the Drosophila enhancer of split genes. Members of this gene family regulate cell differentiation in numerous cell types. The protein encoded by this gene functions as a cofactor, interacting with other transcription factors through a tetrapeptide domain in its C-terminus. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Dec 2008]

GeneCards Summary for HES6 Gene

HES6 (Hes Family BHLH Transcription Factor 6) is a Protein Coding gene. Diseases associated with HES6 include Mood Disorder and Brain Cancer. Among its related pathways are PI3K-Akt signaling pathway and Notch Signaling Pathway (sino). Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein dimerization activity. An important paralog of this gene is HES4.

UniProtKB/Swiss-Prot Summary for HES6 Gene

  • Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation (By similarity).

Gene Wiki entry for HES6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HES6 Gene

Genomics for HES6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HES6 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
GH02J238239 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 -0.7 -687 5.9 RNF2 SP1 HNRNPL GATAD2A CTCF PRDM10 TFE3 NFKBIZ KDM1A POLR2A HES6 ENSG00000225057 ILKAP LINC02610 TRAF3IP1 ERFE PER2 ENSG00000232306 RBM44 ESPNL
GH02J238059 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 8.9 +179.9 179861 3.6 ZNF221 SP1 HNRNPL CREB1 GATAD2A PRDM10 ZNF629 TFE3 IKZF1 NFKBIZ SCLY lnc-ILKAP-6 ESPNL ILKAP UBE2F HES6 KLHL30 UBE2F-SCLY
GH02J237963 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 5.6 +273.9 273887 6.2 CEBPG SP1 CREB1 GATAD2A ZNF629 TFE3 LEF1 IKZF1 NFKBIZ ZNF692 UBE2F UBE2F-SCLY lnc-ILKAP-5 ILKAP SCLY ENSG00000227252 RAMP1 TRAF3IP1 ENSG00000225057 ESPNL
GH02J238096 Promoter/Enhancer 1 EPDnew Ensembl ENCODE 9.5 +144.1 144061 1.2 TEAD4 ZIC2 USF1 POLR2A SIN3A USF2 NR3C1 SCLY ESPNL HES6 lnc-ILKAP-4 UBE2F-SCLY
GH02J238214 Enhancer 0.6 Ensembl dbSUPER 12 +23.9 23861 1.2 SP1 YY1 RAD21 HNF4A RXRA HNF4G piR-51855-019 HES6 ERFE TRAF3IP1 RAMP1 lnc-ERFE-2 lnc-ILKAP-2 ILKAP
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HES6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HES6

Top Transcription factor binding sites by QIAGEN in the HES6 gene promoter:
  • Elk-1
  • MyoD
  • Nkx3-1

Genomic Locations for HES6 Gene

Genomic Locations for HES6 Gene
chr2:238,238,267-238,240,662
(GRCh38/hg38)
Size:
2,396 bases
Orientation:
Minus strand
chr2:239,146,908-239,149,303
(GRCh37/hg19)
Size:
2,396 bases
Orientation:
Minus strand

Genomic View for HES6 Gene

Genes around HES6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HES6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HES6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HES6 Gene

Proteins for HES6 Gene

  • Protein details for HES6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96HZ4-HES6_HUMAN
    Recommended name:
    Transcription cofactor HES-6
    Protein Accession:
    Q96HZ4
    Secondary Accessions:
    • A8KAP6
    • B8ZZA9
    • Q53SN9
    • Q8N2J2
    • Q96T93
    • Q9P2S3

    Protein attributes for HES6 Gene

    Size:
    224 amino acids
    Molecular mass:
    24129 Da
    Quaternary structure:
    • Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with HES1 (By similarity).

    Alternative splice isoforms for HES6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HES6 Gene

Post-translational modifications for HES6 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for HES6 Gene

Domains & Families for HES6 Gene

Gene Families for HES6 Gene

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

Protein Domains for HES6 Gene

InterPro:
Blocks:
  • Basic helix-loop-helix dimerization domain bHLH
  • Orange
ProtoNet:

Suggested Antigen Peptide Sequences for HES6 Gene

GenScript: Design optimal peptide antigens:
  • Hairy and enhancer of split 6 (HES6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96HZ4

UniProtKB/Swiss-Prot:

HES6_HUMAN :
  • The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.
Domain:
  • The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.
  • Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).
genes like me logo Genes that share domains with HES6: view

Function for HES6 Gene

Molecular function for HES6 Gene

UniProtKB/Swiss-Prot Function:
Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation (By similarity).

Phenotypes From GWAS Catalog for HES6 Gene

Gene Ontology (GO) - Molecular Function for HES6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IBA 21873635
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity TAS 10851137
genes like me logo Genes that share ontologies with HES6: view
genes like me logo Genes that share phenotypes with HES6: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HES6

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HES6 Gene

Localization for HES6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HES6 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 HES6 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nuclear bodies (2)
  • Nucleoli (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HES6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA 21873635
GO:0005667 transcription factor complex ISS 10851137
genes like me logo Genes that share ontologies with HES6: view

Pathways & Interactions for HES6 Gene

genes like me logo Genes that share pathways with HES6: view

Pathways by source for HES6 Gene

1 Sino Biological pathway for HES6 Gene
2 BioSystems pathways for HES6 Gene
1 KEGG pathway for HES6 Gene

SIGNOR curated interactions for HES6 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for HES6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IBA 21873635
GO:0006355 regulation of transcription, DNA-templated TAS 10851137
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 HES6: view

Drugs & Compounds for HES6 Gene

No Compound Related Data Available

Transcripts for HES6 Gene

mRNA/cDNA for HES6 Gene

3 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
9 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 HES6

Alternative Splicing Database (ASD) splice patterns (SP) for HES6 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b
SP1:
SP2:
SP3:

Relevant External Links for HES6 Gene

GeneLoc Exon Structure for
HES6

Expression for HES6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HES6 Gene

mRNA differential expression in normal tissues according to GTEx for HES6 Gene

This gene is overexpressed in Pituitary (x4.8).

Protein differential expression in normal tissues from HIPED for HES6 Gene

This gene is overexpressed in Plasma (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HES6 Gene



Protein tissue co-expression partners for HES6 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HES6

SOURCE GeneReport for Unigene cluster for HES6 Gene:

Hs.42949

Evidence on tissue expression from TISSUES for HES6 Gene

  • Nervous system(4.2)
  • Skin(2.9)
  • Liver(2.2)
  • Kidney(2.1)
  • Lung(2)
genes like me logo Genes that share expression patterns with HES6: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for HES6 Gene

Orthologs for HES6 Gene

This gene was present in the common ancestor of chordates.

Orthologs for HES6 Gene

Organism Taxonomy Gene Similarity Type Details
Dog
(Canis familiaris)
Mammalia HES6 30 31
  • 87.77 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HES6 30 31
  • 87.5 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hes6 30
  • 84.01 (n)
Mouse
(Mus musculus)
Mammalia Hes6 30 17 31
  • 83.93 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HES6 31
  • 64 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia HES6 31
  • 61 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HES6 31
  • 26 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HES6 31
  • 58 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hes6.1 30
  • 62.78 (n)
Str.1144 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.209 30
Zebrafish
(Danio rerio)
Actinopterygii her13 30 31
  • 56.71 (n)
OneToMany
hes6 30 31
  • 52 (a)
OneToMany
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6961 30
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9097 31
  • 17 (a)
OneToOne
Species where no ortholog for HES6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Chimpanzee (Pan troglodytes)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • 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 HES6 Gene

ENSEMBL:
Gene Tree for HES6 (if available)
TreeFam:
Gene Tree for HES6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HES6: view image

Paralogs for HES6 Gene

Paralogs for HES6 Gene

(3) SIMAP similar genes for HES6 Gene using alignment to 7 proteins:

  • HES6_HUMAN
  • B8ZZA9_HUMAN
  • B8ZZP9_HUMAN
  • B9A070_HUMAN
  • C9JF41_HUMAN
  • H7C020_HUMAN
  • H7C1R4_HUMAN
genes like me logo Genes that share paralogs with HES6: view

Variants for HES6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HES6 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs3739061 - p.Arg218Gln

Additional dbSNP identifiers (rs#s) for HES6 Gene

Structural Variations from Database of Genomic Variants (DGV) for HES6 Gene

Variant ID Type Subtype PubMed ID
dgv7349n54 CNV loss 21841781
esv21505 CNV loss 19812545
nsv1000252 CNV loss 25217958
nsv584761 CNV gain 21841781
nsv584764 CNV gain 21841781
nsv584766 CNV gain 21841781

Variation tolerance for HES6 Gene

Gene Damage Index Score: 2.60; 45.00% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HES6 Gene

Human Gene Mutation Database (HGMD)
HES6
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HES6

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HES6 Gene

Disorders for HES6 Gene

MalaCards: The human disease database

(3) MalaCards diseases for HES6 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
mood disorder
  • episodic mood disorder
brain cancer
  • adult brain tumor
suppression of tumorigenicity 12
  • st12
- elite association - COSMIC cancer census association via MalaCards
Search HES6 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HES6

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with HES6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HES6 Gene

Publications for HES6 Gene

  1. The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. (PMID: 10851137) Bae S … Kageyama R (Development (Cambridge, England) 2000) 2 3 4 23
  2. A common variant in DRD3 receptor is associated with autism spectrum disorder. (PMID: 19058789) de Krom M … van Ree JM (Biological psychiatry 2009) 3 41
  3. Expression and association analyses of promoter variants of the neurogenic gene HES6, a candidate gene for mood disorder susceptibility and antidepressant response. (PMID: 19481584) Glubb DM … Kennedy MA (Neuroscience letters 2009) 3 41
  4. Integrative genomic analyses on HES/HEY family: Notch-independent HES1, HES3 transcription in undifferentiated ES cells, and Notch-dependent HES1, HES5, HEY1, HEY2, HEYL transcription in fetal tissues, adult tissues, or cancer. (PMID: 17611704) Katoh M … Katoh M (International journal of oncology 2007) 3 23
  5. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4

Products for HES6 Gene

Sources for HES6 Gene