NELL2
protein-codingneural EGFL like 2
Gene summary
The protein encoded by this gene is a glycoprotein containing several von Willebrand factor C domains and epidermal growth factor (EGF)-like domains. The encoded protein acts as a homotrimer and is found in the cytoplasm. Several variants encoding a few different isoforms exist, and at least one isoform appears to be a secreted protein. Studies in mouse suggest that this protein plays a role in neural cell growth and differentiation as well as in oncogenesis. [provided by RefSeq, Feb 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~413.6 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 NELL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145108.2. 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 | 1 | 4 | |||
| missense | 144 | 144 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 153 | 1 | 0 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001138580.1 | 20 | MANE Select | |
| Ensembl | ENSP00000390680.2 | 20 | MANE Select | |
| RefSeq | NP_001138579.1 | 21 | Standard | |
| RefSeq | NP_001138581.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Regulation of commissural axon pathfinding by SLIT and ROBO
- Signaling by ROBO receptors
- Axon guidance
Biological Process
- neuron cellular homeostasis
Molecular Function
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- cell
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000437801
- Coding exons
- 21
- Length
- 413574
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.730 | 435 | 480 | 0.906 | 0.0000245 | 5744 |
| Missense (PolyPhen) | 141 | 189.61 | 0.74364 | 2288 | ||
| Synonymous | 0.00238 | 170 | 170 | 1.00 | 0.00000880 | 1549 |
| Loss of Function | 5.84 | 7 | 52.9 | 0.132 | 0.00000285 | 611 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for neuron survival through the modulation of MAPK pathways (By similarity). Involved in the regulation of hypothalamic GNRH secretion and the control of puberty (By similarity). {ECO:0000250|UniProtKB:Q62918}.;
Recessive Scores
- pRec
- 0.134
Intolerance Scores
- LoFtool
- 0.0196
- RVIS EVS
- -0.62
- RVIS percentile EVS
- 17.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.582
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |