NUMBL Gene (NUMB Like Endocytic Adaptor Protein)
Key regulator of cell fate determination, endocytosis, and Notch signaling
Gene Information Card
| Symbol | NUMBL |
|---|---|
| Full Name | NUMB like, endocytic adaptor protein |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 9253 ncbi.nlm.nih.gov/gene/9253 |
| Ensembl ID | ENSG00000104879 |
| UniProt ID | Q9Y6R0 |
| OMIM ID | 604018 |
| HGNC ID | 8062 |
| Aliases | NBL, NUMB-R, hNUMB |
Description
NUMBL (NUMB like) is a protein-coding gene that encodes an endocytic adaptor protein involved in cell fate determination, asymmetric cell division, and endocytosis. It functions as a negative regulator of Notch signaling by promoting the endocytosis and degradation of the Notch receptor. NUMBL is structurally and functionally related to NUMB and plays roles in neurogenesis, muscle development, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | NUMBL overexpression may promote tumor growth via Notch pathway dysregulation | PMID: 23431147 |
| Lung cancer | Altered NUMBL expression linked to poor prognosis and Notch signaling activation | PMID: 25605248 |
| Neurodevelopmental disorders | NUMBL mutations implicated in impaired neuronal differentiation | PMID: 21572415 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 4.3 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | Moderate expression |
| HeLa | 8.9 | Moderate expression |
| A549 | 6.2 | Low expression |
| MCF7 | 12.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown functional effect |
| c.457G>A (p.Val153Ile) | Missense | <0.01% | Possibly benign |
| c.832_833del (p.Leu278fs) | Frameshift | <0.01% | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Leu278fs) predicted to truncate the protein, impairing endocytic adaptor function and Notch regulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in NUMBL.
Dominant Negative (DN)
No dominant-negative mutations described for NUMBL.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Endocytosis (Reactome: R-HSA-199991)
• Asymmetric cell division (Reactome: R-HSA-2029481)
Protein Summary
NUMBL is a 609-amino acid endocytic adaptor protein containing an N-terminal phosphotyrosine-binding (PTB) domain and C-terminal NPF motifs. It localizes to endosomes and the plasma membrane, where it binds to components of the endocytic machinery (e.g., Eps15, AP-2) and regulates Notch receptor internalization and degradation. NUMBL is essential for asymmetric cell division in neural progenitors and myoblasts, and its dysregulation contributes to oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NUMBL Knockout HEK293 Cell Line | EDJ-KQ441 | Human | 9253 | Details Get a Quote |
| NUMBL Knockout A-549 Cell Line | EDJ-KQ18742 | Human | 9253 | Details Get a Quote |
| NUMBL Knockout HCT 116 Cell Line | EDJ-KQ18743 | Human | 9253 | Details Get a Quote |
| NUMBL Knockout HeLa Cell Line | EDJ-KQ18744 | Human | 9253 | Details Get a Quote |
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