UNC5B Gene: Netrin Receptor in Axon Guidance and Angiogenesis
Comprehensive genomic, expression, and clinical insights into UNC5B, a transmembrane netrin receptor implicated in developmental biology and cancer.
Gene Information Card
| Symbol | UNC5B |
|---|---|
| Full Name | unc-5 netrin receptor B |
| Gene Type | protein-coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 219699 ncbi.nlm.nih.gov/gene/219699 |
| Ensembl ID | ENSG00000155313 |
| UniProt ID | Q8IZJ1 |
| OMIM ID | 607896 |
| HGNC ID | 12568 |
| Aliases | UNC5H2, p53R2 |
Description
UNC5B encodes a transmembrane receptor for netrin-1, a secreted axon guidance molecule. It mediates neuronal guidance, angiogenesis, and apoptosis. In the absence of netrin-1, UNC5B triggers apoptosis, acting as a dependence receptor. It is involved in vascular development and has been implicated in tumor suppression, particularly in colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Loss of UNC5B expression or promoter methylation leads to evasion of apoptosis, promoting tumorigenesis. | COSMIC; PMID: 15635413 |
| Breast Cancer | Reduced UNC5B expression correlates with poor prognosis; netrin-1/UNC5B pathway dysregulation. | COSMIC; PMID: 21930775 |
| Lung Cancer | UNC5B methylation and silencing contribute to tumor progression. | COSMIC; PMID: 22198284 |
| Neuroblastoma | UNC5B acts as a dependence receptor; loss of expression may promote tumor survival. | COSMIC; PMID: 15635413 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 5.2 | Low |
| Kidney | 6.4 | Low |
| Colon | 4.1 | Low |
| Breast | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 15.2 | High expression; involved in angiogenesis |
| SH-SY5Y (neuroblastoma) | 9.8 | Moderate; neuronal lineage |
| MCF7 (breast cancer) | 2.1 | Low; reduced expression in cancer |
| A549 (lung cancer) | 1.5 | Low; silenced in some tumors |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1-?_*?del (whole gene deletion) | Copy number loss | Rare | Loss of function; associated with cancer |
| c.1234C>T (p.Arg412Ter) | Nonsense | 0.01% | Truncated protein; loss of function |
| c.567G>A (p.Met189Ile) | Missense | 0.05% | Unknown; possibly damaging |
| Promoter methylation | Epigenetic | Common in tumors | Silencing of gene expression |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) or epigenetic silencing reduce UNC5B protein levels, impairing apoptosis and promoting tumor growth.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression may occur in some contexts but not well characterized.
Dominant Negative (DN)
Truncated forms could potentially act as dominant-negative by interfering with receptor signaling, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • netrin receptor activity | • transmembrane signaling receptor activity |
| • apoptotic process | • axon guidance |
| • angiogenesis | • cell migration |
Pathways
• Netrin signaling
• Axon guidance
• Apoptosis
• Angiogenesis
Protein Summary
UNC5B is a type I transmembrane protein of 945 amino acids. It has extracellular immunoglobulin-like and thrombospondin domains, and intracellular death domains. It binds netrin-1 with high affinity. In the absence of netrin-1, UNC5B recruits caspase activators to induce apoptosis. It is essential for vascular patterning and neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UNC5B Knockout HEK293 Cell Line | EDJ-KQ3562 | Human | 219699 | Details Get a Quote |
| UNC5B Knockout HCT 116 Cell Line | EDJ-KQ25429 | Human | 219699 | Details Get a Quote |
| UNC5B Knockout HeLa Cell Line | EDJ-KQ59095 | Human | 219699 | Details Get a Quote |
| UNC5B Knockout A-549 Cell Line | EDJ-KQ67571 | Human | 219699 | Details Get a Quote |
