NEUROD2

Chr 17AD

neuronal differentiation 2

Also known as: DEE72, EIEE72, NDRF, bHLHa1

NCBI Gene: 4761 ENSG00000171532 UniProt: Q15784 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.331 OMIM phenotype

Clinical Summary— NEUROD2

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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.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 88 VUS of 110 total submissions

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 OE?0.00 (0.00–0.33)

0≤0.351.4

Missense OE?0.47 (0.40–0.56)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 0 / 9.0Missense obs/exp: 96 / 203.0Syn Z: 0.01

This gene — mechanism propensity

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

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic4

VUS88

Likely Benign8

Benign3

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	4	0	0	4
Likely Pathogenic	0	4	0	0	4
VUS	9	76	2	1	88
Likely Benign	0	4	1	3	8
Benign	0	0	0	3	3
Conflicting	—				3
Total	9	88	3	7	110

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap NEUROD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →