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 encoded protein forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. Expression of this gene is induced by the Notch signal transduction pathway. Two si... See more...

Aliases for HEY2 Gene

Aliases for HEY2 Gene

  • Hes Related Family BHLH Transcription Factor With YRPW Motif 2 2 3 5
  • BHLHb32 2 3 4
  • HERP1 2 3 4
  • Hairy/Enhancer-Of-Split Related With YRPW Motif Protein 2 3 4
  • Hairy/Enhancer-Of-Split Related With YRPW Motif 2 2 3
  • Hairy And Enhancer Of Split-Related Protein 2 3 4
  • Class B Basic Helix-Loop-Helix Protein 32 3 4
  • Cardiovascular Helix-Loop-Helix Factor 1 3 4
  • Hairy-Related Transcription Factor 2 3 4
  • HES-Related Repressor Protein 2 3 4
  • Protein Gridlock Homolog 3 4
  • HESR-2 3 4
  • HESR2 2 3
  • HRT-2 3 4
  • HCHF1 3 4
  • HHRT2 3 4
  • CHF1 3 4
  • HRT2 3 4
  • GRL 3 4
  • Hes-Related Family BHLH Transcription Factor With YRPW Motif 2 2
  • Cardiovascular Basic Helix-Loop-Helix Factor 1 3
  • HES-Related Repressor Protein 1 3
  • GRIDLOCK 3
  • BHLHB32 4
  • HEY2 5
  • HERP 4

External Ids for HEY2 Gene

Previous GeneCards Identifiers for HEY2 Gene

  • GC06P125917
  • GC06P126003
  • GC06P126051
  • GC06P126112
  • GC06P126068
  • GC06P123645

Summaries for HEY2 Gene

Entrez Gene Summary for HEY2 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 encoded protein forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. Expression of this gene is induced by the Notch signal transduction pathway. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for HEY2 Gene

HEY2 (Hes Related Family BHLH Transcription Factor With YRPW Motif 2) is a Protein Coding gene. Diseases associated with HEY2 include Tricuspid Atresia and Chronic Apical Periodontitis. Among its related pathways are Signaling by GPCR and Heart Development. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription factor binding. An important paralog of this gene is HEY1.

UniProtKB/Swiss-Prot Summary for HEY2 Gene

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

Gene Wiki entry for HEY2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HEY2 Gene

Genomics for HEY2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HEY2 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 HEY2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HEY2

Top Transcription factor binding sites by QIAGEN in the HEY2 gene promoter:
  • CREB
  • deltaCREB
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1a
  • MyoD
  • MZF-1
  • NF-AT1
  • Nkx6-1

Genomic Locations for HEY2 Gene

Genomic Locations for HEY2 Gene
chr6:125,747,639-125,762,243
(GRCh38/hg38)
Size:
14,605 bases
Orientation:
Plus strand
chr6:126,068,810-126,082,415
(GRCh37/hg19)
Size:
13,606 bases
Orientation:
Plus strand

Genomic View for HEY2 Gene

Genes around HEY2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HEY2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HEY2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HEY2 Gene

Proteins for HEY2 Gene

  • Protein details for HEY2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBP5-HEY2_HUMAN
    Recommended name:
    Hairy/enhancer-of-split related with YRPW motif protein 2
    Protein Accession:
    Q9UBP5

    Protein attributes for HEY2 Gene

    Size:
    337 amino acids
    Molecular mass:
    35808 Da
    Quaternary structure:
    • May self-associate (By similarity). Interacts with GATA4, HES1 and HEYL (By similarity). Interacts with HDAC1, NCOR1 and SIN3A (By similarity). Interacts with ARNT and GATA6.

neXtProt entry for HEY2 Gene

Post-translational modifications for HEY2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HEY2 Gene

No data available for DME Specific Peptides for HEY2 Gene

Domains & Families for HEY2 Gene

Gene Families for HEY2 Gene

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

Protein Domains for HEY2 Gene

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

Suggested Antigen Peptide Sequences for HEY2 Gene

GenScript: Design optimal peptide antigens:
  • Protein gridlock homolog (HEY2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UBP5

UniProtKB/Swiss-Prot:

HEY2_HUMAN :
  • Belongs to the HEY family.
Family:
  • Belongs to the HEY family.
genes like me logo Genes that share domains with HEY2: view

Function for HEY2 Gene

Molecular function for HEY2 Gene

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

Phenotypes From GWAS Catalog for HEY2 Gene

Gene Ontology (GO) - Molecular Function for HEY2 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 IDA,ISM 19274049
GO:0001102 RNA polymerase II activating transcription factor binding IPI 16293227
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IEA,ISS --
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with HEY2: view
genes like me logo Genes that share phenotypes with HEY2: view

Animal Models for HEY2 Gene

MGI Knock Outs for HEY2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HEY2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HEY2 Gene

Localization for HEY2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HEY2 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 HEY2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Aggresome (2)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HEY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA,ISS --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,ISS --
GO:0016580 colocalizes_with Sin3 complex IDA 11486045
genes like me logo Genes that share ontologies with HEY2: view

Pathways & Interactions for HEY2 Gene

genes like me logo Genes that share pathways with HEY2: view

SIGNOR curated interactions for HEY2 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for HEY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,IMP 11486045
GO:0001568 blood vessel development IEA --
GO:0001570 vasculogenesis IEA,ISS --
GO:0003150 muscular septum morphogenesis IEA,ISS --
GO:0003151 outflow tract morphogenesis IEA,ISS --
genes like me logo Genes that share ontologies with HEY2: view

Drugs & Compounds for HEY2 Gene

No Compound Related Data Available

Transcripts for HEY2 Gene

mRNA/cDNA for HEY2 Gene

1 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
2 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 HEY2

Alternative Splicing Database (ASD) splice patterns (SP) for HEY2 Gene

No ASD Table

Relevant External Links for HEY2 Gene

GeneLoc Exon Structure for
HEY2

Expression for HEY2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HEY2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HEY2 Gene

This gene is overexpressed in Artery - Tibial (x11.1), Heart - Left Ventricle (x5.1), and Artery - Coronary (x4.5).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HEY2

SOURCE GeneReport for Unigene cluster for HEY2 Gene:

Hs.144287

Evidence on tissue expression from TISSUES for HEY2 Gene

  • Heart(4.7)
  • Lung(4.5)
  • Muscle(2.9)
  • Nervous system(2.8)
  • Skin(2.7)
  • Kidney(2.4)
  • Bone marrow(2.3)
  • Pancreas(2.2)
  • Liver(2.1)
  • Eye(2)
  • Blood(2)
genes like me logo Genes that share expression patterns with HEY2: 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 HEY2 Gene

Orthologs for HEY2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HEY2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HEY2 30 31
  • 99.6 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HEY2 31
  • 94 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia HEY2 30 31
  • 90.31 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HEY2 30 31
  • 87.58 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Hey2 30 17 31
  • 86.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hey2 30
  • 86.84 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia HEY2 31
  • 74 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LOC100858839 30
  • 79.07 (n)
Lizard
(Anolis carolinensis)
Reptilia HEY2 31
  • 90 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hey2 30
  • 73.19 (n)
Zebrafish
(Danio rerio)
Actinopterygii hey2 30 31
  • 70.47 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Hey 31 32
  • 28 (a)
OneToMany
Species where no ortholog for HEY2 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)
  • 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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HEY2 Gene

ENSEMBL:
Gene Tree for HEY2 (if available)
TreeFam:
Gene Tree for HEY2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HEY2: view image

Paralogs for HEY2 Gene

Paralogs for HEY2 Gene

(3) SIMAP similar genes for HEY2 Gene using alignment to 2 proteins:

  • HEY2_HUMAN
  • Q5TF93_HUMAN
genes like me logo Genes that share paralogs with HEY2: view

Variants for HEY2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HEY2 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
708201 Likely Benign: not provided 125,759,677(+) G/A MISSENSE_VARIANT
778251 Benign: not provided 125,752,066(+) T/G SYNONYMOUS_VARIANT
790587 Benign: not provided 125,752,098(+) A/T INTRON_VARIANT
rs3734638 - p.Val140Met
rs747221103 - p.Thr96Ala

Additional dbSNP identifiers (rs#s) for HEY2 Gene

Variation tolerance for HEY2 Gene

Residual Variation Intolerance Score: 55.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.20; 52.09% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HEY2 Gene

Human Gene Mutation Database (HGMD)
HEY2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HEY2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for HEY2 Gene

Disorders for HEY2 Gene

MalaCards: The human disease database

(18) MalaCards diseases for HEY2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
tricuspid atresia
  • congenital agenesis of the tricuspid valve
chronic apical periodontitis
tricuspid valve stenosis
  • tricuspid stenosis
aortic valve disease 1
  • aovd1
proctitis
- elite association - COSMIC cancer census association via MalaCards
Search HEY2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HEY2

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 HEY2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HEY2 Gene

Publications for HEY2 Gene

  1. HERP, a new primary target of Notch regulated by ligand binding. (PMID: 11486044) Iso T … Hamamori Y (Molecular and cellular biology 2001) 3 4 23
  2. 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 4
  3. 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
  4. HEY2 mutations in malformed hearts. (PMID: 16329098) Reamon-Buettner SM … Borlak J (Human mutation 2006) 3 4
  5. CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6. (PMID: 16293227) Shirvani S … Chin MT (Biochemical and biophysical research communications 2006) 3 4

Products for HEY2 Gene

Sources for HEY2 Gene