NUMB
protein-codingNUMB endocytic adaptor protein
Gene summary
The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
- C14orf41
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~191.1 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 NUMB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001005743.2. 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 | 1 | 3 | 4 | |||
| missense | 74 | 1 | 75 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 78 | 2 | 3 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001005743.1 | 10 | MANE Select | |
| Ensembl | ENSP00000451300.1 | 10 | MANE Select | |
| RefSeq | NP_001005744.1 | 9 | Standard | |
| RefSeq | NP_001005745.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| numb | Danio rerio | Structure: erythroid lineage cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Notch signaling pathway - Homo sapiens (human)
- NOTCH-Ncore
- Notch Signaling Pathway
- Notch Signaling Pathway
- Notch Signaling Pathway
Biological Process
- axonogenesis
- lateral ventricle development
- neuroblast division in subventricular zone
- positive regulation of cell migration
- adherens junction organization
Molecular Function
- protein binding
- beta-catenin binding
- alpha-catenin binding
- cadherin binding
Cellular Component
- nucleus
- early endosome
- plasma membrane
- focal adhesion
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355058
- Coding exons
- 10
- Length
- 188534
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.37 | 303 | 378 | 0.802 | 0.0000206 | 4245 |
| Missense (PolyPhen) | 89 | 133.38 | 0.66725 | 1425 | ||
| Synonymous | -0.228 | 136 | 133 | 1.03 | 0.00000695 | 1341 |
| Loss of Function | 3.15 | 9 | 26.5 | 0.340 | 0.00000126 | 311 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage.;
Recessive Scores
- pRec
- 0.264
Intolerance Scores
- LoFtool
- 0.806
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |