NEUROD2
protein-codingneuronal differentiation 2, the group of Basic helix-loop-helix proteins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0032710
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0032710
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0032710
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0100062
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: Neurologic
Rationale: The condition can include refractory seizures and other neurologic manifestations, and placement of a vagal-nerve stimulator has been reported as benefiting seizure control as well as development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEUROD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006160.4. 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 | 11 | 1 | 13 | ||
| missense | 4 | 5 | 86 | 7 | 102 | |
| nonsense | 7 | 7 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 5 | 98 | 18 | 1 | 126 |
Highest pathogenic variant AF is 0.0000065930876
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006151.3 | 1 | MANE Select | |
| Ensembl | ENSP00000306754.4 | 1 | MANE Select | |
| Ensembl | ENSP00000577689.1 | 1 | Standard | |
| Ensembl | ENSP00000577689.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- behavioral fear response
- regulation of transcription by RNA polymerase II
- nervous system development
- associative learning
- protein ubiquitination
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- transcription corepressor activity
- protein heterodimerization activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302584
- Coding exons
- 1
- Length
- 6242
- Individuals with no LoFs
- 123173
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123174
- p
- 0.00000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.67 | 96 | 203 | 0.473 | 0.00000932 | 2393 |
| Missense (PolyPhen) | 23 | 83.776 | 0.27454 | 929 | ||
| Synonymous | 0.0146 | 95 | 95.2 | 0.998 | 0.00000467 | 808 |
| Loss of Function | 2.78 | 0 | 9.01 | 0.00 | 3.85e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.00010 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator implicated in neuronal determination. Mediates calcium-dependent transcription activation by binding to E box-containing promoter. Critical factor essential for the repression of the genetic program for neuronal differentiation; prevents the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Induces transcription of ZEB1, which in turn represses neuronal differentiation by down-regulating REST expression. Plays a role in the establishment and maturation of thalamocortical connections; involved in the segregation of thalamic afferents into distinct barrel domains within layer VI of the somatosensory cortex. Involved in the development of the cerebellar and hippocampal granular neurons, neurons in the basolateral nucleus of amygdala and the hypothalamic-pituitary axis. Associates with chromatin to the DPYSL3 E box-containing promoter (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.0402
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.621
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |