NEURL1
protein-codingneuralized E3 ubiquitin protein ligase 1, the group of Ring finger proteins
Gene summary
Predicted to enable translation regulator activity and ubiquitin protein ligase activity. Involved in negative regulation of Notch signaling pathway; negative regulation of cell population proliferation; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
- NEURL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.8 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 NEURL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004210.5. 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 | 3 | 3 | ||||
| missense | 90 | 90 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 90 | 3 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004201.3 | 6 | MANE Select | |
| Ensembl | ENSP00000358795.4 | 6 | MANE Select | |
| Ensembl | ENSP00000416709.1 | 3 | Standard | |
| Ensembl | ENSP00000387714.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| neurl1aa | Danio rerio | Structure: atrial cardiac muscle cell action potential Quality: increased duration abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NOTCH-Ncore
- Disease
- Signal Transduction
- Signaling by NOTCH1
- Signaling by NOTCH2
Biological Process
- regulation of translation
- protein monoubiquitination
- Notch signaling pathway
- sperm axoneme assembly
- nervous system development
Molecular Function
- ubiquitin-protein transferase activity
- translation factor activity, non-nucleic acid binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- plasma membrane
- postsynaptic density
- cell junction
- dendritic spine
- perikaryon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369780
- Coding exons
- 6
- Length
- 98574
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125746
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.54 | 211 | 344 | 0.614 | 0.0000242 | 3618 |
| Missense (PolyPhen) | 65 | 144.57 | 0.44962 | 1440 | ||
| Synonymous | 0.388 | 156 | 162 | 0.961 | 0.0000132 | 1227 |
| Loss of Function | 2.32 | 6 | 16.0 | 0.374 | 7.78e-7 | 179 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0062 | 0.0021 | notable |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in hippocampal-dependent synaptic plasticity, learning and memory. Involved in the formation of spines and functional synaptic contacts by modulating the translational activity of the cytoplasmic polyadenylation element- binding protein CPEB3. Promotes ubiquitination of CPEB3, and hence induces CPEB3-dependent mRNA translation activation of glutamate receptor GRIA1 and GRIA2. Can function as an E3 ubiquitin-protein ligase to activate monoubiquitination of JAG1 (in vitro), thereby regulating the Notch pathway. Acts as a tumor suppressor; inhibits malignant cell transformation of medulloblastoma (MB) cells by inhibiting the Notch signaling pathway. {ECO:0000269|PubMed:20847082}.;
Recessive Scores
- pRec
- 0.111
Essentials
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |