NLE1
protein-codingnotchless homolog 1, the group of WD repeat domain containing
Gene summary
Predicted to be involved in regulation of Notch signaling pathway. Predicted to act upstream of or within several processes, including chordate embryonic development; hematopoietic stem cell homeostasis; and positive regulation of canonical Wnt signaling pathway. Located in nucleolus. [provided by Alliance of Genome Resources, Jun 2026]
- NLE
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.6 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 NLE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018096.5. 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 | 1 | 1 | 1 | 3 | ||
| missense | 67 | 2 | 69 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 3 | 1 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060566.2 | 13 | MANE Select | |
| Ensembl | ENSP00000413572.3 | 13 | MANE Select | |
| RefSeq | NP_001014445.1 | 6 | Standard | |
| Ensembl | ENSP00000354075.5 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- ribosomal large subunit assembly
- somitogenesis
- kidney development
- inner cell mass cell differentiation
- Notch signaling pathway
Cellular Component
- nucleus
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000442241
- Coding exons
- 13
- Length
- 13563
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.563 | 271 | 298 | 0.908 | 0.0000178 | 3121 |
| Missense (PolyPhen) | 92 | 115.61 | 0.79576 | 1197 | ||
| Synonymous | 0.740 | 112 | 122 | 0.915 | 0.00000727 | 991 |
| Loss of Function | 3.02 | 11 | 28.3 | 0.388 | 0.00000149 | 287 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000053 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in regulating Notch activity. Plays a role in regulating the expression of CDKN1A and several members of the Wnt pathway, probably via its effects on Notch activity. Required during embryogenesis for inner mass cell survival (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.203
Intolerance Scores
- LoFtool
- 0.723
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.66
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |