NEUROD1: A Key Transcription Factor in Neuroendocrine Differentiation and Diabetes
Comprehensive gene card, expression, mutations, and clinical significance of NEUROD1
Gene Information Card
| Symbol | NEUROD1 |
|---|---|
| Full Name | Neuronal Differentiation 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q31.3 |
| NCBI Gene ID | 4760 ncbi.nlm.nih.gov/gene/4760 |
| Ensembl ID | ENSG00000162992 |
| UniProt ID | Q13562 |
| OMIM ID | 601724 |
| HGNC ID | 7762 |
| Aliases | BETA2, BHF-1, MODY6, NEUROD, bHLHa3 |
Description
NEUROD1 (Neuronal Differentiation 1) is a basic helix-loop-helix (bHLH) transcription factor that plays a critical role in the development and maintenance of the endocrine pancreas and nervous system. It regulates the expression of insulin and other genes essential for pancreatic beta-cell function. Mutations in NEUROD1 are associated with maturity-onset diabetes of the young type 6 (MODY6) and neonatal diabetes. The gene is also implicated in neuroendocrine tumors and neuronal differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young 6 (MODY6) | Loss-of-function mutations impair insulin gene transcription and beta-cell development | ClinVar, OMIM |
| Neonatal Diabetes Mellitus | Homozygous or compound heterozygous mutations disrupt pancreatic development | ClinVar, OMIM |
| Neuroendocrine Tumors | Overexpression or gain-of-function may drive neuroendocrine differentiation | COSMIC, literature |
| Type 2 Diabetes | Common variants (e.g., rs1801262) may modulate risk | NCBI, GWAS catalog |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 27.8 | High |
| Brain (cerebellum) | 12.3 | Medium |
| Brain (cortex) | 8.5 | Medium |
| Small intestine | 5.1 | Low |
| Stomach | 3.2 | Low |
| Lung | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta-cell) | High | Endogenous expression |
| MIN6 (mouse beta-cell) | High | Endogenous expression |
| SH-SY5Y (neuroblastoma) | Medium | Neuronal model |
| HeLa | Low | Ectopic expression studies |
| HEK293 | Not detected | Negative control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg111Leu (R111L) | Missense | Rare | Loss of DNA binding and transactivation |
| p.Glu59Lys (E59K) | Missense | Rare | Impaired dimerization and function |
| p.Pro197Thr (P197T) | Missense | Rare | Reduced transcriptional activity |
| p.Arg200Gln (R200Q) | Missense | Rare | Associated with MODY6 |
| c.427C>T (p.Arg143*) | Nonsense | Very rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NEUROD1 mutations in MODY6 and neonatal diabetes are loss-of-function, impairing DNA binding, dimerization, or transactivation of target genes (e.g., insulin).
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression in neuroendocrine tumors may act as an oncogenic driver.
Dominant Negative (DN)
Some missense mutations (e.g., R111L) can exert dominant-negative effects by forming nonfunctional dimers with wild-type NEUROD1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin secretion (Reactome: R-HSA-422085)
• Regulation of beta-cell development (KEGG: hsa04950)
• Transcriptional regulation of pancreatic development (Reactome: R-HSA-5617472)
• Neurogenesis (Reactome: R-HSA-9675108)
Protein Summary
NEUROD1 is a 356-amino acid basic helix-loop-helix (bHLH) transcription factor that forms heterodimers with E12/E47 proteins to bind E-box sequences (CANNTG) in target gene promoters. It is essential for the differentiation of pancreatic beta-cells and neurons. The protein contains a bHLH domain (residues 110-159) required for DNA binding and dimerization, and a transactivation domain in the C-terminus. Post-translational modifications include phosphorylation, which modulates its activity. UniProt ID: Q13562.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEUROD1 Knockout HEK293 Cell Line | EDJ-KQ3626 | Human | 4760 | Details Get a Quote |
| NEUROD1 Knockout HeLa Cell Line | EDJ-KQ53985 | Human | 4760 | Details Get a Quote |
| NEUROD1 Knockout A-549 Cell Line | EDJ-KQ62476 | Human | 4760 | Details Get a Quote |
| NEUROD1 Knockout HCT 116 Cell Line | EDJ-KQ70943 | Human | 4760 | Details Get a Quote |
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