LLGL1: Lethal Giant Larvae Homolog 1 – A Key Regulator of Cell Polarity and Tumor Suppression
Comprehensive genomic and functional analysis of LLGL1, a human homolog of the Drosophila lethal giant larvae tumor suppressor gene.
Gene Information Card
| Symbol | LLGL1 |
|---|---|
| Full Name | LLGL1, scribble cell polarity complex component |
| Gene Type | protein-coding |
| Chromosomal Location | 17p12 |
| NCBI Gene ID | 3996 ncbi.nlm.nih.gov/gene/3996 |
| Ensembl ID | ENSG00000131899 |
| UniProt ID | Q15334 |
| OMIM ID | 600966 |
| HGNC ID | 6628 |
| Aliases | DLG4, HUGL, HUGL-1, LGL1, Mgl1, scribble cell polarity complex component |
Description
LLGL1 (lethal giant larvae homolog 1) encodes a cytoskeletal protein that is a core component of the Scribble polarity complex. It regulates cell polarity, asymmetric cell division, and proliferation. Loss of LLGL1 function disrupts apical-basal polarity and is implicated in tumorigenesis, particularly in breast, prostate, and colorectal cancers. The gene also plays a role in neurodevelopment, with mutations linked to intellectual disability and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of LLGL1 disrupts cell polarity and promotes epithelial-mesenchymal transition (EMT), leading to invasion and metastasis. | PMID: 23431136; COSMIC |
| Colorectal cancer | LLGL1 downregulation correlates with poor prognosis; loss of polarity contributes to aberrant crypt formation. | PMID: 20526339; NCBI Gene |
| Prostate cancer | Reduced LLGL1 expression is associated with increased cell proliferation and migration via mislocalization of polarity proteins. | PMID: 21804532; COSMIC |
| Intellectual disability, autosomal dominant 66 | Heterozygous missense mutations in LLGL1 impair neuronal polarity and synaptic function. | PMID: 28991257; ClinVar |
| Epilepsy, focal, with speech disorder and with or without intellectual disability | De novo variants in LLGL1 disrupt protein function, leading to altered neuronal migration. | PMID: 28991257; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Breast | 8.3 | Low |
| Colon | 6.1 | Low |
| Prostate | 7.9 | Low |
| Lung | 9.4 | Low |
| Liver | 4.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 10.2 | Moderate expression |
| HCT116 (colorectal cancer) | 8.7 | Low expression |
| PC3 (prostate cancer) | 7.5 | Low expression |
| SH-SY5Y (neuroblastoma) | 14.1 | High expression |
| HEK293 (embryonic kidney) | 11.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379Cys) | Missense | Rare | Loss of function; disrupts LRR domain and protein stability |
| c.1432G>A (p.Gly478Arg) | Missense | Rare | Dominant negative; impairs binding to Scribble complex |
| c.1861C>T (p.Arg621*) | Nonsense | Very rare | Loss of function; premature truncation |
| c.214_215insA (p.Thr72Asnfs*5) | Frameshift | Very rare | Loss of function; null allele |
Mutation functional classification
Loss of Function (LOF)
Most LLGL1 mutations in cancer and neurodevelopmental disorders are loss-of-function, leading to polarity defects and increased proliferation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for LLGL1.
Dominant Negative (DN)
Missense variants (e.g., p.Gly478Arg) act as dominant-negative by disrupting Scribble complex assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa:04530 – Tight junction
• hsa:05200 – Pathways in cancer
• hsa:05206 – MicroRNAs in cancer
• hsa:04810 – Regulation of actin cytoskeleton
• hsa:04390 – Hippo signaling pathway
Protein Summary
LLGL1 encodes a 1,097-amino-acid protein containing 16 LRR (leucine-rich repeat) domains and a C-terminal LGL domain. It localizes to the apical membrane and cytoplasm, where it scaffolds the Scribble polarity complex. The protein regulates asymmetric cell division by controlling spindle orientation and cell fate determination. In cancer, LLGL1 loss promotes EMT, invasion, and metastasis. In neurons, it is essential for dendritic spine morphogenesis and synaptic plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LLGL1 Knockout HEK293 Cell Line | EDJ-KQ1383 | Human | 3996 | Details Get a Quote |
| LLGL1 Knockout HCT 116 Cell Line | EDJ-KQ19551 | Human | 3996 | Details Get a Quote |
| LLGL1 Knockout A-549 Cell Line | EDJ-KQ20894 | Human | 3996 | Details Get a Quote |
| LLGL1 Knockout HeLa Cell Line | EDJ-KQ20895 | Human | 3996 | Details Get a Quote |
