This gene encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The sequence of the encoded protein contains a conserved bHLH and orange domain, but its YRPW motif has diverged from other HESR family members. It is thought to be an effector of Notch signaling and a regulator of cell fate decisions.... See more...

Aliases for HEYL Gene

Aliases for HEYL Gene

  • Hes Related Family BHLH Transcription Factor With YRPW Motif Like 2 3 5
  • BHLHb33 2 3 4
  • Hairy/Enhancer-Of-Split Related With YRPW Motif-Like Protein 3 4
  • Hairy/Enhancer-Of-Split Related With YRPW Motif 3 2 3
  • Class B Basic Helix-Loop-Helix Protein 33 3 4
  • Hairy-Related Transcription Factor 3 3 4
  • HESR3 2 3
  • HRT-3 3 4
  • HHRT3 3 4
  • HHeyL 3 4
  • HEY3 2 3
  • HRT3 3 4
  • Hes-Related Family BHLH Transcription Factor With YRPW Motif-Like 2
  • Hairy/Enhancer-Of-Split Related With YRPW Motif-Like 2
  • HEY-Like Protein 3
  • BHLHB33 4
  • HEYL 5

External Ids for HEYL Gene

Previous GeneCards Identifiers for HEYL Gene

  • GC01M040119
  • GC01M039093
  • GC01M039553
  • GC01M039503
  • GC01M039492
  • GC01M039741
  • GC01M039862
  • GC01M038207

Summaries for HEYL Gene

Entrez Gene Summary for HEYL Gene

  • This gene encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The sequence of the encoded protein contains a conserved bHLH and orange domain, but its YRPW motif has diverged from other HESR family members. It is thought to be an effector of Notch signaling and a regulator of cell fate decisions. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for HEYL Gene

HEYL (Hes Related Family BHLH Transcription Factor With YRPW Motif Like) is a Protein Coding gene. Diseases associated with HEYL include Deep Corneal Vascularisation and Cerebellopontine Angle Meningioma. Among its related pathways are Signaling by GPCR and Signaling by NOTCH1. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is HEY2.

UniProtKB/Swiss-Prot Summary for HEYL Gene

  • Downstream effector of Notch signaling which may be required for cardiovascular development (By similarity). Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (By similarity). Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.

Gene Wiki entry for HEYL Gene

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

Genomics for HEYL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HEYL Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the HEYL gene promoter:
  • AREB6
  • CREB
  • deltaCREB
  • E47
  • LCR-F1
  • SRF
  • SRF (504 AA)
  • Tal-1
  • Tal-1beta

Genomic Locations for HEYL Gene

Genomic Locations for HEYL Gene
chr1:39,623,435-39,639,643
(GRCh38/hg38)
Size:
16,209 bases
Orientation:
Minus strand
chr1:40,089,103-40,105,617
(GRCh37/hg19)
Size:
16,515 bases
Orientation:
Minus strand

Genomic View for HEYL Gene

Genes around HEYL on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HEYL Gene

Proteins for HEYL Gene

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

    Protein Symbol:
    Q9NQ87-HEYL_HUMAN
    Recommended name:
    Hairy/enhancer-of-split related with YRPW motif-like protein
    Protein Accession:
    Q9NQ87
    Secondary Accessions:
    • Q5TG99

    Protein attributes for HEYL Gene

    Size:
    328 amino acids
    Molecular mass:
    35087 Da
    Quaternary structure:
    • Self-associates. Interacts with GATA4, GATA6, HES1, HEY1 and HEY2. Interacts with HDAC1, NCOR1 and SIN3A.

neXtProt entry for HEYL Gene

Post-translational modifications for HEYL Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HEYL Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HEYL Gene

Domains & Families for HEYL Gene

Gene Families for HEYL Gene

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

Protein Domains for HEYL Gene

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

Suggested Antigen Peptide Sequences for HEYL Gene

GenScript: Design optimal peptide antigens:
  • Hairy-related transcription factor 3 (HEYL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NQ87

UniProtKB/Swiss-Prot:

HEYL_HUMAN :
  • Belongs to the HEY family.
Family:
  • Belongs to the HEY family.
genes like me logo Genes that share domains with HEYL: view

Function for HEYL Gene

Molecular function for HEYL Gene

UniProtKB/Swiss-Prot Function:
Downstream effector of Notch signaling which may be required for cardiovascular development (By similarity). Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (By similarity). Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.
UniProtKB/Swiss-Prot Induction:
By activation of the Notch signaling pathway.

Phenotypes From GWAS Catalog for HEYL Gene

Gene Ontology (GO) - Molecular Function for HEYL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IDA,ISM 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IEA,ISS --
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA --
genes like me logo Genes that share ontologies with HEYL: view
genes like me logo Genes that share phenotypes with HEYL: view

Animal Models for HEYL Gene

MGI Knock Outs for HEYL:
  • Heyl Heyl<tm1.2Abmu>
  • Heyl Heyl<tm1Gess>
  • Heyl Heyl<tm1Kkb>
  • Heyl Heyl<tm1b(KOMP)Wtsi>

Animal Model Products

CRISPR Products

miRNA for HEYL Gene

miRTarBase miRNAs that target HEYL

Inhibitory RNA Products

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

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

Localization for HEYL Gene

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

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for HEYL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA,IDA 21454491
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,ISS --
genes like me logo Genes that share ontologies with HEYL: view

Pathways & Interactions for HEYL Gene

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

SIGNOR curated interactions for HEYL Gene

Is activated by:

Gene Ontology (GO) - Biological Process for HEYL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IBA 21873635
GO:0003151 outflow tract morphogenesis IEA,ISS --
GO:0003180 aortic valve morphogenesis TAS 20951801
GO:0003181 atrioventricular valve morphogenesis IEA,ISS --
GO:0003184 pulmonary valve morphogenesis IEA,ISS --
genes like me logo Genes that share ontologies with HEYL: view

Drugs & Compounds for HEYL Gene

No Compound Related Data Available

Transcripts for HEYL Gene

mRNA/cDNA for HEYL Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 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 HEYL

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

No ASD Table

Relevant External Links for HEYL Gene

GeneLoc Exon Structure for
HEYL

Expression for HEYL Gene

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

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

This gene is overexpressed in Artery - Coronary (x6.7), Artery - Tibial (x4.2), and Pancreas (x4.0).

Protein differential expression in normal tissues from HIPED for HEYL Gene

This gene is overexpressed in Islet of Langerhans (69.0).

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



Protein tissue co-expression partners for HEYL Gene

- Elite partner

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

SOURCE GeneReport for Unigene cluster for HEYL Gene:

Hs.472566

Evidence on tissue expression from TISSUES for HEYL Gene

  • Muscle(4.5)
  • Eye(2.7)
  • Heart(2.5)
  • Nervous system(2.1)
  • Lung(2.1)
genes like me logo Genes that share expression patterns with HEYL: view

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

Orthologs for HEYL Gene

This gene was present in the common ancestor of animals.

Orthologs for HEYL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HEYL 30 31
  • 99.39 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HEYL 30
  • 88.45 (n)
Cow
(Bos Taurus)
Mammalia HEYL 30 31
  • 86.89 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Heyl 30 17 31
  • 82 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Heyl 30
  • 81.95 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia HEYL 31
  • 61 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HEYL 31
  • 58 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HEYL 30 31
  • 66.88 (n)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii heyl 30 31
  • 59.13 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Hey 31 32
  • 26 (a)
OneToMany
Species where no ortholog for HEYL 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)
  • 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)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HEYL Gene

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

Paralogs for HEYL Gene

Paralogs for HEYL Gene

(6) SIMAP similar genes for HEYL Gene using alignment to 2 proteins:

  • HEYL_HUMAN
  • F5H3V9_HUMAN
genes like me logo Genes that share paralogs with HEYL: view

Variants for HEYL Gene

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

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs784625 - p.His47Arg

Additional dbSNP identifiers (rs#s) for HEYL Gene

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

Variant ID Type Subtype PubMed ID
esv3367103 CNV duplication 20981092
nsv1116447 OTHER inversion 24896259
nsv566 CNV insertion 18451855
nsv7177 OTHER inversion 18451855
nsv829649 CNV loss 17160897

Variation tolerance for HEYL Gene

Residual Variation Intolerance Score: 78.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.64; 31.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HEYL Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for HEYL Gene

MalaCards: The human disease database

(10) MalaCards diseases for HEYL Gene - From: DISEASES

Disorder Aliases PubMed IDs
deep corneal vascularisation
  • deep vascularization of cornea
cerebellopontine angle meningioma
  • meningioma of the cerebellar pontine angle
anterior dislocation of lens
cataract 40
  • ctrct40
aortic valve disease 1
  • aovd1
- elite association - COSMIC cancer census association via MalaCards
Search HEYL in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with HEYL: view

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

Publications for HEYL Gene

  1. Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family. (PMID: 10860664) Steidl C … Gessler M (Genomics 2000) 2 3 4 23
  2. Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism. (PMID: 15485867) Kathiriya IS … Nakagawa O (The Journal of biological chemistry 2004) 3 4
  3. Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes. (PMID: 10964718) Maier MM … Gessler M (Biochemical and biophysical research communications 2000) 3 4
  4. Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling. (PMID: 11095750) Nakagawa O … Olson EN (Proceedings of the National Academy of Sciences of the United States of America 2000) 3 4
  5. Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. (PMID: 10415358) Leimeister C … Gessler M (Mechanisms of development 1999) 2 3

Products for HEYL Gene

Sources for HEYL Gene