NEUROD2

Chr 17AD

neuronal differentiation 2

Also known as: DEE72, EIEE72, NDRF, bHLHa1

NCBI Gene: 4761ENSG00000171532UniProt: Q15784

This gene encodes a member of the neuroD family of neurogenic basic helix-loop-helix (bHLH) proteins. Expression of this gene can induce transcription from neuron-specific promoters, such as the GAP-43 promoter, which contain a specific DNA sequence known as an E-box. The product of the human gene can induce neurogenic differentiation in non-neuronal cells in Xenopus embryos, and is thought to play a role in the determination and maintenance of neuronal cell fates. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 72MIM #618374
AD
120
ClinVar variants
16
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
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.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 89 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.47 (0.40–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 0 / 9.0Missense obs/exp: 96 / 203.0Syn Z: 0.01

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic4
VUS89
Likely Benign9
Benign3
Conflicting3
12
Pathogenic
4
Likely Pathogenic
89
VUS
9
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
8
0
12
Likely Pathogenic
0
4
0
0
4
VUS
3
71
14
1
89
Likely Benign
0
4
2
3
9
Benign
0
0
0
3
3
Conflicting
—3
Total383247120

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 72

MIM #618374

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.
Singh AK et al.·Brain
2024
Expansion of NEUROD2 phenotypes to include developmental delay without seizures.
Mis EK et al.·Am J Med Genet A
2021Case report
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
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
NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family.
McCormick MB et al.·Mol Cell Biol
1996
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
Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.
Demarest S et al.·Dev Med Child Neurol
2022
Chromosome 17 copy number changes in male breast cancer.
Lacle MM et al.·Cell Oncol (Dordr)
2015
Epileptic spasms related to neuronal differentiation factor 2 (NEUROD2) mutation respond to combined vigabatrin and high dose prednisolone therapy.
Sakpichaisakul K et al.·BMC Neurol
2022Case report
Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations.
Takagi Y et al.·Neurol Med Chir (Tokyo)
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
2025🔓 Open Access
NeuroD2 Modulates Hippocampal Neuronal Organization and Axon Guidance During Aging.
Beker M et al.·In Vivo
2025🔓 Open Access
Unraveling the Role of NeuroD2 in Ischemic Pathophysiology: Insight into Neuroprotection Mechanisms Associated with AKT Survival Kinase.
Bolat B et al.·Neuromolecular Med
2025🔓 Open 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
2024🔓 Open AccessFunctional
NEUROD2 function is dispensable for human pancreatic β cell specification.
Cota P et al.·Front Endocrinol (Lausanne)
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools