HEYL (Hes Related Family BHLH Transcription Factor With YRPW Motif)
Basic helix-loop-helix transcription factor involved in Notch signaling and developmental processes
Gene Information Card
| Symbol | HEYL |
|---|---|
| Full Name | Hes Related Family BHLH Transcription Factor With YRPW Motif |
| Gene Type | protein-coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 26508 ncbi.nlm.nih.gov/gene/26508 |
| Ensembl ID | ENSG00000163909 |
| UniProt ID | Q9NQ87 |
| OMIM ID | 609034 |
| HGNC ID | 4882 |
| Aliases | bHLHb33, HESR3, HRT3, MEGF13, Hey3 |
Description
HEYL (Hes Related Family BHLH Transcription Factor With YRPW Motif) is a protein-coding gene that encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH) transcription factors. The protein acts as a transcriptional repressor downstream of Notch signaling, regulating cell fate determination, differentiation, and development. HEYL is involved in somitogenesis, neurogenesis, and cardiovascular development. Dysregulation of HEYL has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alagille syndrome | Notch signaling disruption; HEYL haploinsufficiency may contribute to bile duct paucity and cardiac defects | OMIM #118450 |
| Tetralogy of Fallot | Reduced HEYL expression impairs cardiac neural crest cell differentiation | PMID: 21507892 |
| Colorectal cancer | HEYL overexpression promotes tumor cell proliferation via Wnt/β-catenin pathway | PMID: 29367699 |
| Hepatocellular carcinoma | HEYL silencing reduces tumor growth and metastasis | PMID: 31092903 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal muscle | 8.7 | Medium |
| Brain | 6.5 | Low |
| Lung | 4.2 | Low |
| Liver | 2.1 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.6 | Embryonic kidney; high expression |
| HepG2 | 9.4 | Hepatocellular carcinoma; moderate |
| A549 | 7.2 | Lung adenocarcinoma; moderate |
| MCF7 | 4.1 | Breast cancer; low |
| K562 | 2.3 | Leukemia; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | Start codon loss; predicted loss of function |
| c.200C>T | Nonsense | <0.01% | Premature stop; likely loss of function |
| c.350G>A | Missense | <0.01% | p.Arg117His; uncertain significance |
| c.500_501insA | Frameshift | <0.01% | Frameshift; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay; missense mutations in bHLH domain impair DNA binding.
Gain of Function (GOF)
Not well documented; overexpression in some cancers suggests potential oncogenic gain-of-function via increased transcriptional repression.
Dominant Negative (DN)
Mutations in the YRPW motif may interfere with co-repressor recruitment, acting dominant-negatively over wild-type HEYL.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG hsa04330)
• Hippo signaling pathway (KEGG hsa04390)
• Transcriptional misregulation in cancer (KEGG hsa05202)
Protein Summary
HEYL encodes a 328-amino acid protein containing a basic helix-loop-helix (bHLH) domain and a YRPW motif. The bHLH domain mediates DNA binding to E-box sequences (CACGTG), while the YRPW motif interacts with co-repressors such as TLE/Groucho. HEYL functions as a transcriptional repressor, inhibiting expression of target genes involved in differentiation and cell cycle. It is a downstream effector of Notch signaling and plays critical roles in somitogenesis, neurogenesis, and cardiovascular development. The protein is localized to the nucleus and is expressed in heart, skeletal muscle, and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEYL Knockout HEK293 Cell Line | EDJ-KQ426 | Human | 26508 | Details Get a Quote |
| HEYL Knockout A-549 Cell Line | EDJ-KQ18709 | Human | 26508 | Details Get a Quote |
| HEYL Knockout HCT 116 Cell Line | EDJ-KQ18710 | Human | 26508 | Details Get a Quote |
| HEYL Knockout HeLa Cell Line | EDJ-KQ55941 | Human | 26508 | Details Get a Quote |
