NEUROD1

Chr 2AD

neuronal differentiation 1

Also known as: BETA2, BHF-1, MODY6, NEUROD, T2D, bHLHa3

NCBI Gene: 4760 ENSG00000162992 UniProt: Q13562 OMIM: 601724

This gene encodes a member of the NeuroD family of basic helix-loop-helix (bHLH) transcription factors. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus. [provided by RefSeq, Jul 2008]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.512 OMIM phenotypes

Clinical Summary— NEUROD1

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Gene-Disease Validity (ClinGen)

monogenic diabetes · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 228 VUS of 339 total submissions

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Clinical Trials

4 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — NEUROD1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.771

Z-score 2.51

OE 0.11 (0.04–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.23Z-score

OE missense 0.95 (0.85–1.07)

191 obs / 200.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.51)

0≤0.351.4

Missense OE?0.95 (0.85–1.07)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 1 / 9.2Missense obs/exp: 191 / 200.3Syn Z: -1.65

This gene — mechanism propensity

0.5180th %ile

GOF

0.2298th %ile

LOF

0.73top 10%

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

LOFprediction above median · 1 literature citation

Literature Evidence

LOFHeterozygous loss-of-function mutations in NEUROD1 have previously been described as a cause of maturity-onset diabetes of the young (MODY) and late-onset diabetes.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 25684977 ↗

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS228

Likely Benign88

Benign8

Conflicting10

Pathogenic

Likely Pathogenic

228

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	1	0	1	2
Likely Pathogenic	0	3	0	0	3
VUS	8	191	28	1	228
Likely Benign	0	1	9	78	88
Benign	0	2	6	0	8
Conflicting	—				10
Total	8	198	43	80	339

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap NEUROD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →