HEY2 Gene - Basic Helix-Loop-Helix Transcriptional Repressor
HEY2: A key regulator of cardiovascular development and Notch signaling
Gene Information Card
| Symbol | HEY2 |
|---|---|
| Full Name | Hes Related Family BHLH Transcription Factor With YRPW Motif 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q22.31 |
| NCBI Gene ID | 23493 ncbi.nlm.nih.gov/gene/23493 |
| Ensembl ID | ENSG00000135547 |
| UniProt ID | Q9UBP5 |
| OMIM ID | 604674 |
| HGNC ID | 4881 |
| Aliases | CHF1, HERP1, HESR2, HRT2, bHLHb32 |
Description
HEY2 (Hes Related Family BHLH Transcription Factor With YRPW Motif 2) is a protein-coding gene that encodes a basic helix-loop-helix (bHLH) transcriptional repressor. It functions downstream of the Notch signaling pathway and plays a critical role in cardiovascular development, particularly in ventricular chamber maturation and coronary artery formation. HEY2 regulates cell fate determination, differentiation, and boundary formation in developing tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ventricular septal defect | Loss-of-function mutations in HEY2 disrupt Notch-mediated transcriptional repression, leading to impaired ventricular septation and myocardial differentiation. | ClinVar, OMIM |
| Tetralogy of Fallot | Rare variants in HEY2 are associated with altered cardiac neural crest cell migration and outflow tract development. | NCBI Gene, ClinVar |
| Congenital heart disease (general) | HEY2 variants contribute to abnormal heart morphogenesis through dysregulation of downstream target genes involved in cardiac development. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 18.2 | High |
| Skeletal muscle | 5.1 | Medium |
| Lung | 3.8 | Medium |
| Brain | 2.4 | Low |
| Liver | 1.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 22.5 | High expression in differentiated cardiac cells |
| HUVEC (endothelial) | 8.3 | Moderate expression in vascular endothelium |
| HeLa | 1.2 | Low expression in cervical cancer line |
| HEK293 | 0.9 | Very low expression in embryonic kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.295C>T (p.Arg99*) | Nonsense | Rare | Loss of function; associated with ventricular septal defect |
| c.416G>A (p.Arg139Gln) | Missense | Rare | Reduced DNA-binding affinity and transcriptional repression activity |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression; linked to congenital heart disease |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the bHLH domain or YRPW motif, impairing DNA binding and transcriptional repression.
Gain of Function (GOF)
Not reported in HEY2; no activating mutations documented.
Dominant Negative (DN)
Missense mutations in the bHLH domain may form non-functional dimers, interfering with wild-type HEY2 and related factors.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Cardiac progenitor differentiation
• Ventricular chamber development
Protein Summary
The HEY2 protein (Q9UBP5) is a 337-amino acid transcriptional repressor belonging to the HES-related family. It contains a basic helix-loop-helix (bHLH) domain for DNA binding and dimerization, an Orange domain for protein-protein interactions, and a C-terminal YRPW motif involved in transcriptional repression. HEY2 forms homodimers or heterodimers with other bHLH factors (e.g., HEY1, HES1) and binds to N-box (CACNAG) or E-box (CANNTG) sequences to repress target gene expression. It is a key effector of Notch signaling in cardiovascular development, regulating cell proliferation, differentiation, and boundary formation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEY2 Knockout HEK293 Cell Line | EDJ-KQ425 | Human | 23493 | Details Get a Quote |
| HEY2 Knockout HeLa Cell Line | EDJ-KQ55749 | Human | 23493 | Details Get a Quote |
| HEY2 Knockout A-549 Cell Line | EDJ-KQ64247 | Human | 23493 | Details Get a Quote |
| HEY2 Knockout HCT 116 Cell Line | EDJ-KQ72693 | Human | 23493 | Details Get a Quote |
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