STK11 (LKB1): A Master Tumor Suppressor Gene in Cancer Genetics
Explore the STK11 gene, its role in Peutz-Jeghers Syndrome, cancer pathways, expression, and clinical significance.
Gene Information Card
| Symbol | STK11 |
|---|---|
| Full Name | Serine/Threonine Kinase 11 |
| Gene Type | Protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 6794 ncbi.nlm.nih.gov/gene/6794 |
| Ensembl ID | ENSG00000118046 |
| UniProt ID | Q15831 |
| OMIM ID | 602216 |
| HGNC ID | 11389 |
| Aliases | LKB1, PJS, hLKB1 |
Description
The STK11 gene encodes serine/threonine kinase 11 (LKB1), a master tumor suppressor that regulates cellular metabolism, cell polarity, and growth. It functions as an upstream kinase of AMPK and AMPK-related kinases, controlling energy homeostasis and mTOR signaling. Germline mutations cause Peutz-Jeghers Syndrome (PJS), and somatic mutations are frequent in various cancers, including lung and pancreatic cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Peutz-Jeghers Syndrome (PJS) | Germline loss-of-function mutations lead to hamartomatous polyps and increased cancer risk. | OMIM 175200; ClinVar |
| Lung adenocarcinoma | Somatic mutations/inactivation of STK11 co-occur with KRAS mutations, promoting tumor progression and immune evasion. | COSMIC; TCGA studies |
| Pancreatic cancer | Somatic loss of STK11 contributes to tumorigenesis, often in the context of KRAS mutations. | COSMIC; literature |
| Cervical cancer | Somatic mutations and loss of heterozygosity at 19p13.3 are observed. | COSMIC |
| Breast cancer | Somatic mutations and promoter methylation have been reported, though less frequent. | COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Lung | 6.3 | Low |
| Pancreas | 5.1 | Low |
| Colon | 4.8 | Low |
| Testis | 12.0 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 9.5 | Hepatocellular carcinoma cell line |
| A549 (lung) | 5.2 | Lung adenocarcinoma |
| MCF7 (breast) | 4.0 | Breast cancer |
| PANC-1 (pancreas) | 3.8 | Pancreatic ductal adenocarcinoma |
| HEK293 (embryonic kidney) | 7.0 | Immortalized kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.580G>T (p.Glu194Ter) | Nonsense | Rare (germline) | Loss of function; truncating protein |
| c.842C>T (p.Pro281Leu) | Missense | Somatic (lung cancer) | Impaired kinase activity |
| c.109C>T (p.Gln37Ter) | Nonsense | Germline (PJS) | Loss of function |
| c.375_376del (p.Leu126fs) | Frameshift | Somatic (pancreatic) | Loss of function |
| c.464G>A (p.Arg155His) | Missense | Somatic (cervical) | Reduced kinase activity |
Mutation functional classification
Loss of Function (LOF)
Most STK11 mutations are loss-of-function, including nonsense, frameshift, and splice-site variants, leading to truncated or absent protein. These are common in PJS and sporadic cancers.
Gain of Function (GOF)
No gain-of-function mutations have been reported; STK11 acts as a tumor suppressor, and activating mutations are not observed.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming inactive dimers, but this is not well-established. Most mutations are haploinsufficient or recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • protein kinase activity | • signal transduction |
| • cell cycle arrest | • regulation of cell growth |
| • response to stress | • cellular response to glucose stimulus |
Pathways
• AMPK signaling pathway
• mTOR signaling pathway
• p53 signaling pathway
• Autophagy regulation
• Cell polarity (PAR complex)
Protein Summary
STK11 (LKB1) is a 433-amino acid serine/threonine kinase that phosphorylates and activates AMPK and 12 other AMPK-related kinases. It forms a complex with STRAD and MO25, which is essential for its catalytic activity and cytoplasmic localization. LKB1 regulates cell polarity, energy metabolism, and apoptosis. Loss of LKB1 leads to uncontrolled cell growth and metabolic dysregulation, contributing to tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STK11 Knockout HEK293 Cell Line | EDJ-KQ869 | Human | 6794 | Details Get a Quote |
| STK11IP Knockout HEK293 Cell Line | EDJ-KQ7462 | Human | 114790 | Details Get a Quote |
| STK11 Knockout A-549 Cell Line | EDJ-KQ19681 | Human | 6794 | Details Get a Quote |
| STK11 Knockout HCT 116 Cell Line | EDJ-KQ19682 | Human | 6794 | Details Get a Quote |
| STK11 Knockout HeLa Cell Line | EDJ-KQ19683 | Human | 6794 | Details Get a Quote |
| STK11IP Knockout A-549 Cell Line | EDJ-KQ32679 | Human | 114790 | Details Get a Quote |
| STK11IP Knockout HCT 116 Cell Line | EDJ-KQ32680 | Human | 114790 | Details Get a Quote |
| STK11IP Knockout HeLa Cell Line | EDJ-KQ32681 | Human | 114790 | Details Get a Quote |
| STK11 (c.375-132A>G )Point Mutation in HAP1 Cell Line | EDC03611 | Human | 6794 | Details Get a Quote |
| STK11 (c.920+7G>A )Point Mutation in HAP1 Cell Line | EDC03612 | Human | 6794 | Details Get a Quote |
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