HEY2 hes related family bHLH transcription factor with YRPW motif 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HEY2provided by HGNC
Official Full Name: hes related family bHLH transcription factor with YRPW motif 2provided by HGNC
Primary source: HGNC:HGNC:4881
See related: Ensembl:ENSG00000135547 MIM:604674; AllianceGenome:HGNC:4881
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GRL; CHF1; HRT2; HERP1; HESR2; bHLHb32; GRIDLOCK
Summary: 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]
Expression: Broad expression in endometrium (RPKM 2.9), brain (RPKM 2.7) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q22.31

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (125749632..125761269)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (126938147..126949784)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (126070778..126082415)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms.
Title: Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms.
TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma.
Title: TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma.
Notch-HEY2 signaling pathway contributes to the differentiation of CD34(+) hematopoietic-like stem cells from adult peripheral blood insulin-producing cells after the treatment with platelet-derived mitochondria.
Title: Notch-HEY2 signaling pathway contributes to the differentiation of CD34(+) hematopoietic-like stem cells from adult peripheral blood insulin-producing cells after the treatment with platelet-derived mitochondria.
microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway.
Title: microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway.
Attenuation of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts to neurons.
Title: Attenuation of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts to neurons.
These results provide evidence that miR-146a and Hey2 form a mutual negative feedback regulatory loop to regulate the inflammatory response in chronic apical periodontitis.
Title: microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis.
we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in non-small cell lung cancer by competitively binding miR-448.
Title: LncRNA PRNCR1 interacts with HEY2 to abolish miR-448-mediated growth inhibition in non-small cell lung cancer.
We also highlighted that Hey2 is involved in radiation-induced EndoMT and that Hey2 invalidation reduces EndoMT and tissue damage.
Title: Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice.
The findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network.
Title: NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.
HEY2 as a promising biomarker for unfavorable outcomes and a novel therapeutic target for the clinical management of HCC
Title: HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

stHey2seq (e-PCR)
- UniSTS:181770

SHGC-78750 (e-PCR)
- UniSTS:95634

HEY2_2351 (e-PCR)
- UniSTS:280751

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in Notch signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in anterior/posterior axis specification	IEA Inferred from Electronic Annotation more info
involved_in anterior/posterior pattern specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in aortic valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in aortic valve morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in arterial endothelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in ascending aorta morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in atrial septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac conduction system development	NAS Non-traceable Author Statement more info	PubMed
involved_in cardiac epithelial to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac left ventricle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cardiac muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in cardiac muscle hypertrophy in response to stress	IEA Inferred from Electronic Annotation more info
involved_in cardiac right ventricle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac vascular smooth muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in cardiac ventricle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell fate commitment	IEA Inferred from Electronic Annotation more info
involved_in circulatory system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in cochlea development	IEA Inferred from Electronic Annotation more info
involved_in coronary vasculature morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in dorsal aorta morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endocardial cushion to mesenchymal transition involved in heart valve formation	IEA Inferred from Electronic Annotation more info
involved_in epithelial to mesenchymal transition involved in endocardial cushion formation	TAS Traceable Author Statement more info	PubMed
involved_in heart trabecula formation	IEA Inferred from Electronic Annotation more info
involved_in labyrinthine layer blood vessel development	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in muscular septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of biomineral tissue development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cardiac vascular smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription initiation by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed
involved_in outflow tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cardiac muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of heart rate	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein-DNA complex assembly	IEA Inferred from Electronic Annotation more info
involved_in pulmonary artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in pulmonary valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of inner ear auditory receptor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of neurogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in smooth muscle cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in tricuspid valve formation	IEA Inferred from Electronic Annotation more info
involved_in tricuspid valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in umbilical cord morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in vascular associated smooth muscle cell development	IEP Inferred from Expression Pattern more info	PubMed
involved_in vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular cardiac muscle cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular trabecula myocardium morphogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
part_of transcription repressor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: hairy/enhancer-of-split related with YRPW motif protein 2

Names: HES-related repressor protein 1; HES-related repressor protein 2; HESR-2; HRT-2; cardiovascular basic helix-loop-helix factor 1; cardiovascular helix-loop-helix factor 1; class B basic helix-loop-helix protein 32; hCHF1; hHRT2; hairy and enhancer of split-related protein 2; hairy-related transcription factor 2; hairy/enhancer-of-split related with YRPW motif 2; protein gridlock homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012259.3 → NP_036391.1 hairy/enhancer-of-split related with YRPW motif protein 2

See identical proteins and their annotated locations for NP_036391.1

Status: REVIEWED

Source sequence(s)

AJ249545, BC007707, BI549391

Consensus CDS

CCDS5131.1

UniProtKB/Swiss-Prot

Q9UBP5

UniProtKB/TrEMBL

A8K1M8

Related

ENSP00000357348.3, ENST00000368364.4

Conserved Domains (2) summary

smart00511
Location:119 → 165

ORANGE; Orange domain

cd18920
Location:40 → 121

bHLH-O_HEY2; basic helix-loop-helix-orange (bHLH-O) domain found in hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

125749632..125761269

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017010628.2 → XP_016866117.1 hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

UniProtKB/TrEMBL

B4E1L3, Q5TF93

Conserved Domains (2) summary

smart00511
Location:73 → 119

ORANGE; Orange domain

cl00081
Location:1 → 75

bHLH_SF; basic Helix Loop Helix (bHLH) domain superfamily
XM_017010627.2 → XP_016866116.1 hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

UniProtKB/TrEMBL

B4E1L3, Q5TF93

Related

ENSP00000357349.1, ENST00000368365.5

Conserved Domains (2) summary

smart00511
Location:73 → 119

ORANGE; Orange domain

cl00081
Location:1 → 75

bHLH_SF; basic Helix Loop Helix (bHLH) domain superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

126938147..126949784

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054354946.1 → XP_054210921.1 hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

UniProtKB/TrEMBL

Q5TF93
XM_054354945.1 → XP_054210920.1 hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1

UniProtKB/TrEMBL

Q5TF93