ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1)
Key regulator of neuroendocrine differentiation and a driver in small cell lung cancer and neuroendocrine tumors
Gene Information Card
| Symbol | ASCL1 |
|---|---|
| Full Name | achaete-scute family bHLH transcription factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q23.2 |
| NCBI Gene ID | 429 ncbi.nlm.nih.gov/gene/429 |
| Ensembl ID | ENSG00000139352 |
| UniProt ID | P50553 |
| OMIM ID | 100790 |
| HGNC ID | 738 |
| Aliases | ASCL1, ASH1, bHLHa46, HASH1, MASH1 |
Description
ASCL1 (achaete-scute family bHLH transcription factor 1) encodes a basic helix-loop-helix (bHLH) transcription factor that plays a critical role in neuronal and neuroendocrine differentiation. It is a master regulator of neurogenesis and is essential for the development of pulmonary neuroendocrine cells. In cancer, ASCL1 is a lineage oncogene in small cell lung cancer (SCLC) and is frequently amplified or overexpressed in neuroendocrine tumors. It promotes cell proliferation, survival, and neuroendocrine phenotype maintenance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Small Cell Lung Cancer (SCLC) | ASCL1 acts as a lineage oncogene; amplification and overexpression drive neuroendocrine differentiation and tumor growth. | COSMIC; NCBI Gene; ClinVar |
| Neuroblastoma | ASCL1 is expressed in neuroblastoma cell lines and tumors; promotes neuronal differentiation and proliferation. | NCBI Gene; UniProt; OMIM |
| Pulmonary Carcinoid Tumor | ASCL1 expression is associated with neuroendocrine differentiation in lung carcinoids. | NCBI Gene; COSMIC |
| Medullary Thyroid Carcinoma | ASCL1 is expressed in medullary thyroid carcinoma, contributing to neuroendocrine phenotype. | NCBI Gene; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Adrenal Gland | 6.1 | Low |
| Thyroid | 4.7 | Low |
| Pancreas | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H69 (SCLC) | 45.2 | High expression; neuroendocrine lineage |
| DMS 53 (SCLC) | 38.7 | High expression; neuroendocrine lineage |
| SH-SY5Y (Neuroblastoma) | 22.1 | Moderate expression |
| HEK293 (Embryonic Kidney) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of function; start codon loss |
| c.217C>T (p.Arg73Trp) | Missense | <0.1% | Unknown significance; in bHLH domain |
| Amplification | Copy number gain | ~15% in SCLC | Gain of function; increased ASCL1 expression |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations in the bHLH domain may impair DNA binding and transcriptional activity, reducing neuroendocrine differentiation.
Gain of Function (GOF)
Gene amplification and overexpression in SCLC lead to sustained neuroendocrine signaling and oncogenic transformation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported in ASCL1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Neurogenesis (KEGG: hsa04722)
• Transcriptional regulation of pluripotent stem cells (KEGG: hsa04550)
• Small cell lung cancer (KEGG: hsa05222)
Protein Summary
ASCL1 is a 236-amino acid basic helix-loop-helix transcription factor that forms heterodimers with E12/E47 proteins to bind E-box DNA sequences. It is essential for the development of neural and neuroendocrine cells. In cancer, particularly small cell lung cancer, ASCL1 acts as a lineage-survival oncogene, driving neuroendocrine differentiation and tumor progression. Its expression is tightly regulated by Notch signaling, and loss of Notch leads to ASCL1 upregulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASCL1 Knockout HEK293 Cell Line | EDJ-KQ50134 | Human | 429 | Details Get a Quote |
| ASCL1 Knockout HeLa Cell Line | EDJ-KQ52669 | Human | 429 | Details Get a Quote |
| ASCL1 Knockout A-549 Cell Line | EDJ-KQ61140 | Human | 429 | Details Get a Quote |
| ASCL1 Knockout HCT 116 Cell Line | EDJ-KQ69629 | Human | 429 | Details Get a Quote |
