HES1: Hairy and Enhancer of Split 1, a Key Transcriptional Repressor in Notch Signaling
Comprehensive biomedical overview of HES1, including gene characteristics, expression, mutations, and disease associations.
Gene Information Card
| Symbol | HES1 |
|---|---|
| Full Name | hairy and enhancer of split 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q29 |
| NCBI Gene ID | 3280 ncbi.nlm.nih.gov/gene/3280 |
| Ensembl ID | ENSG00000114315 |
| UniProt ID | Q14469 |
| OMIM ID | 139605 |
| HGNC ID | 5192 |
| Aliases | HES-1, HHL, HRY, bHLHb39 |
Description
HES1 (hairy and enhancer of split 1) is a basic helix-loop-helix (bHLH) transcriptional repressor that functions as a key downstream effector of the Notch signaling pathway. It regulates cell differentiation, proliferation, and neurogenesis by repressing target genes such as ASCL1 and NEUROG1. HES1 is widely expressed in embryonic and adult tissues, with roles in stem cell maintenance and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | HES1 overexpression promotes tumor cell proliferation and metastasis via Notch pathway activation | PMID: 25609812 |
| Colorectal cancer | HES1 upregulation correlates with poor prognosis and resistance to chemotherapy | PMID: 27498884 |
| Neuroblastoma | HES1 suppresses neuronal differentiation, contributing to tumor aggressiveness | PMID: 23542344 |
| Alzheimer's disease | HES1 dysregulation in neural stem cells may impair neurogenesis | PMID: 21533022 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 5.1 | Low |
| Kidney | 7.9 | Low |
| Testis | 15.2 | Medium |
| Placenta | 18.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.4 | High expression in embryonic kidney cells |
| HeLa | 14.1 | Moderate expression in cervical cancer cells |
| MCF7 | 19.8 | High expression in breast cancer cells |
| SH-SY5Y | 11.3 | Moderate expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | missense | 0.01% | p.Met1Val; may affect translation initiation |
| c.200C>T | nonsense | 0.005% | p.Gln67*; premature truncation, loss of function |
| c.350G>A | missense | 0.02% | p.Arg117Gln; altered DNA-binding affinity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the bHLH domain or C-terminal WRPW motif impair transcriptional repression.
Gain of Function (GOF)
Missense mutations that enhance DNA binding or stability may increase repression of differentiation genes, promoting oncogenesis.
Dominant Negative (DN)
Mutations that disrupt dimerization or DNA binding but retain the WRPW motif can interfere with wild-type HES1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
• Signaling pathways regulating pluripotency of stem cells (KEGG: hsa04550)
Protein Summary
HES1 is a 280-amino-acid nuclear protein containing a bHLH domain for DNA binding and a C-terminal WRPW motif that recruits co-repressors such as TLE/Groucho. It forms homodimers or heterodimers with other bHLH factors to repress transcription of genes involved in differentiation. HES1 is a critical regulator of cell fate decisions in development and is frequently dysregulated in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HES1 Knockout HEK293 Cell Line | EDJ-KQ128 | Human | 3280 | Details Get a Quote |
| HES1 Knockout A-549 Cell Line | EDJ-KQ18703 | Human | 3280 | Details Get a Quote |
| HES1 Knockout HCT 116 Cell Line | EDJ-KQ18705 | Human | 3280 | Details Get a Quote |
| HES1 Knockout HeLa Cell Line | EDJ-KQ18706 | Human | 3280 | Details Get a Quote |
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