NEUROD2

Chr 17AD

neuronal differentiation 2

Also known as: DEE72, EIEE72, NDRF, bHLHa1

NCBI Gene: 4761ENSG00000171532UniProt: Q15784OMIM: 601725

NEUROD2 encodes a basic helix-loop-helix transcription factor that regulates neuronal differentiation and development, particularly in cerebellar and hippocampal granule neurons, and is involved in establishing thalamocortical connections. Mutations cause developmental and epileptic encephalopathy 72 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.94), reflecting its critical role in neurodevelopment.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.331 OMIM phenotype
Clinical Summary— NEUROD2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.942
Z-score 2.78
OE 0.00 (0.00–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.67Z-score
OE missense 0.47 (0.40–0.56)
96 obs / 203.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.33)
0≤0.351.4
Missense OE0.47 (0.40–0.56)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 0 / 9.0Missense obs/exp: 96 / 203.0Syn Z: 0.01
DN
0.3694th %ile
GOF
0.2298th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.33

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NEUROD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Expansion of NEUROD2 phenotypes to include developmental delay without seizures.
Mis EK et al.·Am J Med Genet A
2021Case report
Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.
Demarest S et al.·Dev Med Child Neurol
2022
p53 and miR-210 regulated NeuroD2, a neuronal basic helix-loop-helix transcription factor, is downregulated in glioblastoma patients and functions as a tumor suppressor under hypoxic microenvironment.
Agrawal R et al.·Int J Cancer
2018Cohort
Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons.
Runge K et al.·Mol Psychiatry
2021
A novel variant in NEUROD2 in a patient with Rett-like phenotype points to Glu130 codon as a mutational hotspot.
Politano D et al.·Brain Dev
2023Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Neurod2 knockdown in Xenopus laevis tadpole brain retains cells in a proliferating, progenitor-like state.
Beck CW et al.·MicroPubl Biol
2026Open Access
Studies of the motifs that regulate subcellular localization reveal differences between the homologous neuronal proteins NeuroD1 and NeuroD2.
Kolonko-Adamska M et al.·Cell Commun Signal
2025Open Access
NeuroD2 Modulates Hippocampal Neuronal Organization and Axon Guidance During Aging.
Beker M et al.·In Vivo
2025Open Access
Unraveling the Role of NeuroD2 in Ischemic Pathophysiology: Insight into Neuroprotection Mechanisms Associated with AKT Survival Kinase.
Bolat B et al.·Neuromolecular Med
2025Open AccessFunctional
Knockdown of NeuroD2 leads to seizure-like behavior, brain neuronal hyperactivity and a leaky blood-brain barrier in a Xenopus laevis tadpole model of DEE75.
Banerjee S et al.·Genetics
2024Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients