NEUROG3
protein-codingneurogenin 3, the group of Basic helix-loop-helix proteins
Gene summary
The protein encoded by this gene is a basic helix-loop-helix (bHLH) transcription factor involved in neurogenesis. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of congenital malabsorptive diarrhea 4 (DIAR4).[provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012479
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012479
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012479
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0100164
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012479
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Gastrointestinal
Intervention: Gastrointestinal
Rationale: Individuals may present in infancy with severe hyperchloremic metabolic acidosis due to vomiting and diarrhea, and may require parenteral nutrition and limited enteral feeding (with oral vitamins and electrolyte supplementation); Surveillance may allow early recognition and treatment of diabetes mellitus (including with insulin); One reported individual required liver/intestinal transplant
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEUROG3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020999.4. 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 | 60 | 1 | 61 | |||
| missense | 2 | 4 | 82 | 4 | 1 | 93 |
| nonsense | 2 | 2 | 1 | 5 | ||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 3 | 7 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 7 | 86 | 64 | 2 | 166 |
Highest pathogenic variant AF is 0.000012391298
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066279.2 | 1 | MANE Select | |
| Ensembl | ENSP00000242462.4 | 1 | MANE Select | |
| Ensembl | ENSP00000599843.1 | 1 | Standard | |
| Ensembl | ENSP00000802281.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Maturity onset diabetes of the young - Homo sapiens (human)
- Notch-mediated HES/HEY network
Biological Process
- negative regulation of transcription by RNA polymerase II
- nervous system development
- central nervous system development
- peripheral nervous system development
- spinal cord development
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- transcription coactivator activity
- protein binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000242462
- Coding exons
- 1
- Length
- 1541
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125713
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.517 | 143 | 127 | 1.13 | 0.00000595 | 1325 |
| Missense (PolyPhen) | 39 | 37.962 | 1.0273 | 421 | ||
| Synonymous | -0.491 | 64 | 59.2 | 1.08 | 0.00000287 | 495 |
| Loss of Function | -0.686 | 7 | 5.30 | 1.32 | 2.46e-7 | 49 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a transcriptional regulator. Together with NKX2- 2, initiates transcriptional activation of NEUROD1. Involved in neurogenesis. Also required for the specification of a common precursor of the 4 pancreatic endocrine cell types (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Diarrhea 4, malabsorptive, congenital (DIAR4) [MIM:610370]: A disease characterized by severe, life-threatening watery diarrhea associated with generalized malabsorption and a paucity of enteroendocrine cells. {ECO:0000269|PubMed:16855267}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.200
Intolerance Scores
- LoFtool
- 0.381
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.283
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |