NEUROD4
protein-codingneuronal differentiation 4, the group of Basic helix-loop-helix proteins
Gene summary
Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and E-box binding activity. Predicted to be involved in neuron differentiation; positive regulation of cell differentiation; and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within Notch signaling pathway; cell fate commitment; and neurogenesis. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEUROD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021191.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 43 | 2 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 43 | 2 | 1 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067014.2 | 1 | MANE Select | |
| Ensembl | ENSP00000242994.3 | 1 | MANE Select | |
| Ensembl | ENSP00000802301.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| neurod4 | Danio rerio | Structure: olfactory placode Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- neuron migration
- regulation of transcription by RNA polymerase II
- Notch signaling pathway
- neuroblast proliferation
- glial cell differentiation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein dimerization activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000242994
- Coding exons
- 1
- Length
- 10070
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 19
- Defined
- 125743
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.567 | 200 | 179 | 1.12 | 0.00000875 | 2173 |
| Missense (PolyPhen) | 75 | 73.538 | 1.0199 | 858 | ||
| Synonymous | -0.845 | 77 | 68.1 | 1.13 | 0.00000330 | 663 |
| Loss of Function | 1.84 | 3 | 8.91 | 0.337 | 5.22e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00023 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably acts as a transcriptional activator. Mediates neuronal differentiation. Required for the regulation of amacrine cell fate specification in the retina (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.243
- RVIS EVS
- 0.88
- RVIS percentile EVS
- 89.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.820
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |