BHLHE40
Basic Helix-Loop-Helix Family Member E40
Gene Information Card
| Symbol | BHLHE40 |
|---|---|
| Full Name | Basic Helix-Loop-Helix Family Member E40 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p26.1 |
| NCBI Gene ID | 8553 ncbi.nlm.nih.gov/gene/8553 |
| Ensembl ID | ENSG00000134107 |
| UniProt ID | O14503 |
| OMIM ID | 604256 |
| HGNC ID | 1046 |
| Aliases | DEC1, SHARP2, BHLHB2, STRA13, HLH1R2 |
Description
BHLHE40 (Basic Helix-Loop-Helix Family Member E40) encodes a transcription factor that belongs to the basic helix-loop-helix (bHLH) family. It functions as a transcriptional repressor involved in the regulation of circadian rhythm, cell differentiation, immune response, and hypoxia adaptation. BHLHE40 represses target genes by binding to E-box elements and interacting with other bHLH proteins. It is also known as DEC1 (Differentiated Embryo Chondrocyte 1) and SHARP2 (Enhancer of Split and Hairy-related Protein 2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | BHLHE40 overexpression promotes tumor growth and metastasis via regulation of cell cycle and apoptosis | PMID: 25605247 |
| Colorectal cancer | BHLHE40 upregulation correlates with poor prognosis and enhances invasion through EMT | PMID: 27121324 |
| Rheumatoid arthritis | BHLHE40 modulates Th17 cell differentiation and inflammatory cytokine production | PMID: 29127259 |
| Circadian rhythm disorders | BHLHE40 represses CLOCK/BMAL1-mediated transcription, affecting sleep-wake cycles | PMID: 11751636 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 15.2 | Medium |
| Kidney | 9.7 | Low |
| Skeletal muscle | 4.8 | Low |
| Testis | 18.9 | Medium |
| Placenta | 22.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 20.1 | High expression |
| HeLa | 15.6 | Medium expression |
| MCF7 | 12.3 | Medium expression |
| A549 | 18.7 | High expression |
| K562 | 8.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511C>T (p.Arg171Trp) | Missense | 0.01% (gnomAD) | Unknown functional impact |
| c.742G>A (p.Gly248Ser) | Missense | 0.005% (gnomAD) | Unknown functional impact |
| c.1003_1004insA (p.Thr335Asnfs*12) | Frameshift | Rare | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr335Asnfs*12) likely result in truncated protein and loss of transcriptional repressor activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in BHLHE40.
Dominant Negative (DN)
Missense mutations in the bHLH domain may interfere with dimerization and DNA binding, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • GO:0000978 – RNA polymerase II cis-regulatory region sequence-specific DNA binding | • GO:0001227 – DNA-binding transcription repressor activity |
| • RNA polymerase II-specific | • GO:0005634 – nucleus |
| • GO:0006357 – regulation of transcription by RNA polymerase II | • GO:0042752 – regulation of circadian rhythm |
| • GO:0001666 – response to hypoxia | • GO:0045892 – negative regulation of transcription |
| • DNA-templated |
Pathways
• Circadian rhythm pathway (Reactome: R-HSA-400253)
• Hypoxia-inducible factor (HIF) signaling (KEGG: hsa04066)
• Notch signaling pathway (KEGG: hsa04330)
Protein Summary
BHLHE40 is a 412-amino acid protein (UniProt O14503) containing a basic helix-loop-helix (bHLH) domain and an Orange domain. It functions as a transcriptional repressor by forming homodimers or heterodimers with other bHLH factors (e.g., HES1) and binding to E-box sequences (CACGTG). BHLHE40 is induced by hypoxia, serum shock, and circadian signals, and it represses target genes such as PER1 and CLOCK. The protein is involved in cell cycle arrest, differentiation, and immune regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BHLHE40 Knockout HEK293 Cell Line | EDJ-KQ2245 | Human | 8553 | Details Get a Quote |
| BHLHE40 Knockout A-549 Cell Line | EDJ-KQ22546 | Human | 8553 | Details Get a Quote |
| BHLHE40 Knockout HCT 116 Cell Line | EDJ-KQ22547 | Human | 8553 | Details Get a Quote |
| BHLHE40 Knockout HeLa Cell Line | EDJ-KQ22548 | Human | 8553 | Details Get a Quote |
| BHLHE40 Knockout HEK293T Cell Line | EDC07836 | Human | 8553 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
