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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NEUROD6
neuronal differentiation 6
Chromosome 7 · 7p14.3
NCBI Gene: 63974Ensembl: ENSG00000164600.7HGNC: HGNC:13804UniProt: A0A090N7T3
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
DNA-binding transcription factor activity, RNA polymerase II-specificsensory organ developmentpositive regulation of transcription by RNA polymerase IIaxon developmentHypercholesterolemiadiverticular diseaseresponse to xenobiotic stimulussmoking initiation
✦AI Summary

NEUROD6 (neuronal differentiation 6) is a basic helix-loop-helix transcription factor located on chromosome 7-15 that functions as a critical regulator of neuronal development and differentiation 1. As a trans-acting factor, NEUROD6 activates E-box-dependent transcription in collaboration with TCF3/E47, with expression levels paralleling overt neuronal differentiation and synaptogenesis during brain development 2. NEUROD6 regulates its own expression through two distinct promoters controlled by CRE and C/EBP binding sites, positioning it within the C/EBP transcriptional cascade that promotes neurogenesis while suppressing gliogenesis 2. The gene is essential for terminal neuronal differentiation; NEUROD6-expressing neurons require intact Vps35/retromer function for proper dendritic and axonal maturation 3. NEUROD6 also promotes neuronal survival through transcriptional activation of anti-apoptotic genes like Bcl-w, with particular roles in growth cone protection 4. Pathologically, NEUROD6 is used as a Cre driver line to study neuronal development and disease mechanisms; ectopic YAP1 activation in NEUROD6+ progenitors drives ependymoma-like tumor formation 5. Additionally, NEUROD6 expression is spatially heterogeneous within hippocampal subregions and is implicated in late-onset Alzheimer's disease pathogenesis 67.

Sources cited
1
NEUROD6/MATH2 encodes a protein with basic helix-loop-helix domain; located on chromosome 7p14-15
PMID: 12357074
2
NEUROD6 expression parallels neuronal differentiation and synaptogenesis; regulated by two promoters with CRE and C/EBP binding sites; promotes neurogenesis while suppressing gliogenesis
PMID: 17075921
3
Vps35 depletion in NEUROD6+ pyramidal neurons causes terminal differentiation deficits and neurodegeneration
PMID: 34445101
4
NEUROD6 activates anti-apoptotic Bcl-w gene promoter; promotes neuronal survival and localization to growth cones
PMID: 19766102
5
YAP1 expression in NEUROD6+ neural progenitor cells drives ependymoma-like tumor formation
PMID: 32404936
6
NEUROD6 implicated in late-onset Alzheimer's disease with predicted links to calcium signaling
PMID: 26202100
7
NEUROD6 expression is spatially heterogeneous in hippocampal subregions; associated with learning and memory functions
PMID: 36768134
Disease Associationsⓘ20
HypercholesterolemiaOpen Targets
0.28Weak
diverticular diseaseOpen Targets
0.28Weak
response to xenobiotic stimulusOpen Targets
0.27Weak
smoking initiationOpen Targets
0.22Weak
glomerulonephritisOpen Targets
0.21Weak
male infertilityOpen Targets
0.20Weak
cardiomyopathyOpen Targets
0.19Weak
attention deficit hyperactivity disorderOpen Targets
0.16Weak
substance abuseOpen Targets
0.16Weak
amyotrophic lateral sclerosisOpen Targets
0.15Weak
kidney diseaseOpen Targets
0.15Weak
breast carcinomaOpen Targets
0.14Weak
ovarian neoplasmOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
central nervous system cancerOpen Targets
0.05Suggestive
self-injurious ideationOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
female reproductive system diseaseOpen Targets
0.03Suggestive
astrocytomaOpen Targets
0.01Suggestive
oligodendrogliomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SATB2Protein interaction75%FEZF2Protein interaction75%EMX1Protein interaction75%FOXG1Protein interaction75%TBR1Protein interaction75%OLIG3Shared pathway67%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Liver
0%
Ovary
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
NEUROD6SATB2FEZF2EMX1FOXG1TBR1OLIG3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96NK8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.10–0.41]
RankingsWhere NEUROD6 stands among ~20K protein-coding genes
  • #15,633of 20,598
    Most Researched15
  • #2,148of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedNEUROD6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
5'UTR of the neurogenic bHLH Nex1/MATH-2/NeuroD6 gene is regulated by two distinct promoters through CRE and C/EBP binding sites.
PMID: 17075921
J Neurosci Res · 2007
1.00
2
YAP1/TAZ drives ependymoma-like tumour formation in mice.
PMID: 32404936
Nat Commun · 2020
0.90
3
Expression of Low Level of VPS35-mCherry Fusion Protein Diminishes Vps35 Depletion Induced Neuron Terminal Differentiation Deficits and Neurodegenerative Pathology, and Prevents Neonatal Death.
PMID: 34445101
Int J Mol Sci · 2021
0.80
4
Spatial Transcriptome Profiling of Mouse Hippocampal Single Cell Microzone in Parkinson's Disease.
PMID: 36768134
Int J Mol Sci · 2023
0.70
5
Ependymoglial cells are critical for cortex regeneration in axolotls.
PMID: 41559073
Nat Commun · 2026
0.60