LNX1: Ligand of Numb-Protein X 1
A RING-type E3 ubiquitin ligase involved in cell fate determination and Notch signaling regulation.
Gene Information Card
| Symbol | LNX1 |
|---|---|
| Full Name | Ligand of Numb-Protein X 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 84708 ncbi.nlm.nih.gov/gene/84708 |
| Ensembl ID | ENSG00000138685 |
| UniProt ID | Q8TBB5 |
| OMIM ID | 609732 |
| HGNC ID | 18799 |
| Aliases | LNX, MGC138207, MGC138209, PDZRN2 |
Description
LNX1 (Ligand of Numb-Protein X 1) encodes a RING-type E3 ubiquitin ligase that interacts with the cell fate determinant Numb. Through its PDZ domains, LNX1 targets Numb and other substrates for ubiquitination and proteasomal degradation, thereby modulating Notch signaling and asymmetric cell division. LNX1 is involved in neurogenesis, epithelial polarity, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | LNX1 variants may alter Numb degradation, affecting neuronal migration and synaptic plasticity. | ClinVar, PMID: 25629512 |
| Breast cancer | Overexpression of LNX1 promotes degradation of Numb, leading to enhanced Notch signaling and tumor growth. | COSMIC, PMID: 20010871 |
| Glioblastoma | LNX1-mediated Numb downregulation contributes to cancer stem cell maintenance via Notch activation. | COSMIC, PMID: 20628086 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells; moderate expression |
| SH-SY5Y | 14.3 | Neuroblastoma cells; high expression |
| MCF7 | 9.7 | Breast cancer cells; moderate expression |
| U87MG | 11.8 | Glioblastoma cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.001% (gnomAD) | May disrupt PDZ domain binding; uncertain significance |
| c.1456G>A (p.Glu486Lys) | Missense | 0.002% (gnomAD) | Located in RING domain; potential loss of E3 ligase activity |
| c.1789_1791del (p.Lys597del) | In-frame deletion | <0.001% | Reported in breast cancer; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Mutations in the RING finger domain (e.g., p.Glu486Lys) are predicted to impair ubiquitin ligase activity, reducing Numb degradation and altering Notch signaling.
Gain of Function (GOF)
Overexpression or amplification of LNX1 (not specific point mutations) is associated with increased Numb turnover and oncogenic Notch activation.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in LNX1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• Signaling by Numb (Reactome: R-HSA-9013408)
Protein Summary
LNX1 is a 737-amino acid protein containing a RING-type zinc finger domain at the C-terminus and four PDZ domains. It functions as an E3 ubiquitin ligase, targeting Numb and other PDZ domain-containing proteins for degradation. LNX1 is localized to the cytoplasm and plasma membrane, and its activity is critical for regulating Notch signaling during development and in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LNX1 Knockout HEK293 Cell Line | EDJ-KQ9404 | Human | 84708 | Details Get a Quote |
| LNX1 Knockout HCT 116 Cell Line | EDJ-KQ37293 | Human | 84708 | Details Get a Quote |
| LNX1 Knockout HeLa Cell Line | EDJ-KQ37294 | Human | 84708 | Details Get a Quote |
| LNX1 Knockout A-549 Cell Line | EDJ-KQ66153 | Human | 84708 | Details Get a Quote |
