NEUROG3 (Neurogenin 3) Gene
Key Regulator of Endocrine Pancreatic Development and Enteroendocrine Cell Differentiation
Gene Information Card
| Symbol | NEUROG3 |
|---|---|
| Full Name | Neurogenin 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 50674 ncbi.nlm.nih.gov/gene/50674 |
| Ensembl ID | ENSG00000122859 |
| UniProt ID | Q9Y4Z2 |
| OMIM ID | 604882 |
| HGNC ID | 7760 |
| Aliases | Ngn3, bHLHa6, Atoh5 |
Description
NEUROG3 (neurogenin 3) encodes a basic helix-loop-helix (bHLH) transcription factor essential for the specification of endocrine cell lineages in the pancreas and intestine. It acts downstream of Notch signaling and upstream of NeuroD1, driving differentiation of pancreatic islet cells (alpha, beta, delta, PP) and enteroendocrine cells. Loss-of-function mutations cause permanent neonatal diabetes with exocrine pancreatic insufficiency and severe malabsorption due to lack of enteroendocrine cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Permanent neonatal diabetes mellitus with pancreatic exocrine insufficiency | Biallelic loss-of-function mutations in NEUROG3 prevent endocrine pancreas development, leading to insulin deficiency and malabsorption. | ClinVar, OMIM |
| Congenital malabsorptive diarrhea (enteropathy) | Absence of enteroendocrine cells due to NEUROG3 deficiency disrupts gut hormone secretion, causing severe diarrhea. | OMIM, PubMed |
| Type 2 diabetes (susceptibility) | Common variants in NEUROG3 may modulate beta-cell mass and function, contributing to T2D risk. | GWAS, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 0.0 | Not detected (transient embryonic expression) |
| Small intestine | 0.0 | Not detected (transient embryonic expression) |
| Brain | 0.0 | Not detected (transient embryonic expression) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PANC-1 (pancreatic ductal) | 0.0 | No endogenous expression |
| HeLa (cervical) | 0.0 | No endogenous expression |
| HEK293 (embryonic kidney) | 0.0 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.82G>A (p.Glu28Lys) | Missense | Rare | Loss of DNA-binding and transactivation activity |
| c.139C>T (p.Arg47*) | Nonsense | Rare | Premature truncation, complete loss of function |
| c.403C>T (p.Arg135Trp) | Missense | Rare | Impaired nuclear localization and transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Most NEUROG3 mutations are recessive loss-of-function, leading to absent or non-functional protein, causing neonatal diabetes and malabsorption.
Gain of Function (GOF)
Not reported in NEUROG3.
Dominant Negative (DN)
Not reported; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling in endocrine pancreas development
• Transcription factor regulation of pancreatic islet cell differentiation
Protein Summary
NEUROG3 is a 214-amino-acid bHLH transcription factor that heterodimerizes with E-proteins (e.g., TCF3) to bind E-box sequences and activate target genes such as NEUROD1. It is transiently expressed in pancreatic and intestinal endocrine progenitors during embryonic development. The protein contains a basic DNA-binding domain and a helix-loop-helix dimerization domain. Loss of function abolishes endocrine cell formation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEUROG3 Knockout HEK293 Cell Line | EDJ-KQ10800 | Human | 50674 | Details Get a Quote |
| NEUROG3 Knockout HeLa Cell Line | EDJ-KQ56181 | Human | 50674 | Details Get a Quote |
| NEUROG3 Knockout A-549 Cell Line | EDJ-KQ64671 | Human | 50674 | Details Get a Quote |
| NEUROG3 Knockout HCT 116 Cell Line | EDJ-KQ73120 | Human | 50674 | Details Get a Quote |
