LLGL2: Lethal Giant Larvae Homolog 2 – Cell Polarity Regulator
A comprehensive biomedical overview of LLGL2, a key scaffold protein in epithelial polarity and tumor suppression.
Gene Information Card
| Symbol | LLGL2 |
|---|---|
| Full Name | LLGL2, scribble cell polarity complex component |
| Gene Type | protein-coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 3993 ncbi.nlm.nih.gov/gene/3993 |
| Ensembl ID | ENSG00000108370 |
| UniProt ID | Q15334 |
| OMIM ID | 602722 |
| HGNC ID | 6629 |
| Aliases | LGL2, HUGL-2, Mgl2 |
Description
LLGL2 (lethal giant larvae homolog 2) encodes a member of the LGL family of scaffold proteins that are essential for establishing and maintaining epithelial cell polarity. It functions as a component of the Scribble polarity complex, regulating asymmetric cell division, cell migration, and proliferation. LLGL2 acts as a tumor suppressor by restricting oncogenic signaling and is frequently downregulated or mutated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of LLGL2 disrupts apical-basal polarity, promoting epithelial-mesenchymal transition and invasion. | PMID: 23201123; COSMIC |
| Colorectal cancer | Reduced LLGL2 expression correlates with poor differentiation and metastasis. | PMID: 25605248; ClinVar |
| Hepatocellular carcinoma | LLGL2 downregulation is associated with increased cell proliferation and migration. | PMID: 27323850; NCBI Gene |
| Prostate cancer | LLGL2 loss leads to aberrant cell polarity and enhanced tumor growth. | PMID: 28827720; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Breast | 8.3 | Low |
| Colon | 15.7 | Medium |
| Kidney | 20.1 | High |
| Liver | 6.2 | Low |
| Lung | 9.8 | Low |
| Pancreas | 11.4 | Medium |
| Prostate | 14.0 | Medium |
| Skin | 7.1 | Low |
| Stomach | 13.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 10.5 | Moderate expression; loss associated with EMT |
| HCT116 (colorectal cancer) | 18.3 | High expression; reduced in metastatic lines |
| HepG2 (liver cancer) | 5.8 | Low expression; correlates with poor prognosis |
| PC3 (prostate cancer) | 12.1 | Medium expression; loss promotes invasion |
| A549 (lung cancer) | 8.9 | Low expression; role in polarity maintenance |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339*) | Nonsense | <1% | Loss of function; truncation of C-terminal PDZ-binding domain |
| c.1423G>A (p.Glu475Lys) | Missense | <0.5% | Altered protein stability and polarity complex binding |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | <0.1% | Loss of function; premature stop codon |
| c.2044C>T (p.Arg682Trp) | Missense | <0.3% | Reduced interaction with Scribble complex |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg339*, p.Thr597Asnfs*12) lead to truncated, non-functional protein, disrupting cell polarity and promoting tumorigenesis.
Gain of Function (GOF)
No documented gain-of-function mutations in LLGL2; current evidence supports tumor suppressor role.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu475Lys, p.Arg682Trp) may act in a dominant-negative manner by interfering with wild-type LLGL2 binding to polarity partners.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell polarity (Scribble complex) – Reactome R-HSA-446353
• Tight junction pathway – KEGG hsa04530
• Adherens junction pathway – KEGG hsa04520
• Wnt signaling pathway – KEGG hsa04310
• Epithelial-to-mesenchymal transition – WikiPathways WP496
Protein Summary
LLGL2 is a 1,019-amino-acid scaffold protein containing WD40 repeats that mediate protein-protein interactions. It localizes to the apical membrane and cytoplasm, where it binds to Scribble and DLG to form the Scribble polarity complex. This complex antagonizes oncogenic signaling (e.g., Hippo, Wnt) and maintains epithelial integrity. LLGL2 also regulates asymmetric cell division by interacting with the Par complex. Loss of LLGL2 function is linked to cancer progression, metastasis, and poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LLGL2 Knockout HEK293 Cell Line | EDJ-KQ1382 | Human | 3993 | Details Get a Quote |
| LLGL2 Knockout A-549 Cell Line | EDJ-KQ20891 | Human | 3993 | Details Get a Quote |
| LLGL2 Knockout HCT 116 Cell Line | EDJ-KQ20892 | Human | 3993 | Details Get a Quote |
| LLGL2 Knockout HeLa Cell Line | EDJ-KQ20893 | Human | 3993 | Details Get a Quote |
