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STK11
serine/threonine kinase 11
The STK11 gene provides instructions for making serine/threonine kinase 11, a crucial enzyme that acts as a tumour suppressor, regulating cell growth, division, and energy use. STK11 encodes a protein vital for preventing uncontrolled cell proliferation and maintaining tissue integrity.
STK11 is located on the short (p) arm of chromosome 19, at band 19p13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The STK11 gene, also known as LKB1, directs the production of an enzyme called serine/threonine kinase 11. This enzyme functions as a tumour suppressor, playing a critical role in controlling how cells grow, divide, and organise within tissues. It helps prevent cells from proliferating too rapidly or in an unregulated manner, thereby safeguarding against cancer development.
Beyond its role in cell cycle regulation, STK11 is also involved in cellular energy metabolism and promoting programmed cell death (apoptosis), processes essential for maintaining healthy tissue. Normal STK11 function is thought to be necessary for proper development before birth.
What the gene does
The STK11 gene produces serine/threonine kinase 11, an enzyme critical for several cellular processes. As a tumour suppressor, it primarily acts to inhibit uncontrolled cell growth and division. This enzyme achieves its tumour suppressive effects by influencing cell polarity, which is the proper orientation of cells within tissues, and by regulating cellular energy homeostasis. It assists in determining the amount of energy a cell uses.
STK11 plays a role in determining how much energy a cell consumes and influences the cellular response to nutrient availability. By modulating metabolic pathways, STK11 helps to ensure that cells only divide when adequate resources are available, preventing the unchecked proliferation characteristic of cancer. Additionally, serine/threonine kinase 11 promotes apoptosis, a process of programmed cell death that eliminates damaged or abnormal cells, further contributing to its tumour suppressor activity. Its functions extend to early development, where it is required for normal embryonic processes.
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Chromosome location
The STK11 gene is located on chromosome 19, specifically at position 19p13.3. This region is found on the short (p) arm of chromosome 19. The precise location of STK11 within the human genome underscores its specific functional roles and its association with inherited conditions.
Protein structure
The STK11 protein, serine/threonine kinase 11, is composed of 433 amino acids. Its functional activity is mediated by distinct structural regions and domains. A key functional area is the Protein kinase domain, spanning amino acids 49-309, which is responsible for the enzyme's catalytic activity-specifically, the phosphorylation of serine and threonine residues on target proteins. This domain is central to STK11's signalling functions.
The protein also contains a region from amino acids 45-90 that is sufficient for interaction with SIRT1. Additionally, there are two identified Disordered regions: one located between amino acids 312-331 and another at the C-terminus, from amino acids 397-433. These disordered regions often play roles in protein-protein interactions and may contribute to the flexibility and regulatory mechanisms of the STK11 protein.
Key variants
Variants within the STK11 gene can lead to changes in the serine/threonine kinase 11 protein, affecting its normal function. These genetic alterations can range from single nucleotide changes (missense or nonsense variants) that alter a single amino acid or introduce a premature stop codon, to larger deletions or insertions that remove or add significant portions of the gene. Pathogenic variants typically impair the protein's ability to act as a tumour suppressor, leading to dysregulation of cell growth, division, and metabolism. Many STK11 gene mutations have been identified in individuals with Peutz-Jeghers syndrome, highlighting the genetic heterogeneity underlying this disorder.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1010_1011del | p.Val337fs | Pathogenic | ★★☆☆ | Peutz-Jeghers syndrome |
c.108C>G | p.Tyr36Ter | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1090C>T | p.Gln364Ter | Pathogenic | ★★☆☆ | Gastric cancer |
c.109C>T | p.Gln37Ter | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.116_117dup | p.Arg40fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.141dup | p.Lys48fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peutz-Jeghers syndrome |
c.147C>G | p.Tyr49Ter | Pathogenic | ★★☆☆ | Peutz-Jeghers syndrome |
c.156_157dup | p.Asp53fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.157del | p.Asp53fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.157dup | p.Asp53fs | Pathogenic | ★★☆☆ | Peutz-Jeghers syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the STK11 gene are primarily associated with Peutz-Jeghers syndrome. This is an inherited condition characterised by the development of distinctive non-cancerous growths called hamartomatous polyps in the gastrointestinal tract and a significantly increased risk of developing several types of cancer. Research indicates that individuals with this syndrome face substantially elevated risks for breast, lung, and ovarian cancers, among others. While STK11 variants account for a substantial proportion of Peutz-Jeghers syndrome cases, they represent only a small fraction of overall cancer diagnoses.
Inheritance pattern
Conditions caused by pathogenic STK11 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
In the UK, the STK11 gene is recognised within several NHS Genomic Medicine Service (GMS) pathways due to its clinical significance. It is a 'green' gene on numerous PanelApp panels, indicating strong evidence for its association with disease. This includes panels for Adult solid tumours cancer susceptibility, Childhood solid tumours, Colorectal cancer pertinent cancer susceptibility, Familial breast cancer, GI tract tumours, Inherited pancreatic cancer (R367), Inherited polyposis and early onset colorectal cancer - germline testing (R211), Peutz Jeghers Syndrome (R212), and Pigmentary skin disorders. Its inclusion on these panels signifies that testing for STK11 variants is considered clinically appropriate for individuals meeting specific criteria within these contexts.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
For individuals with pathogenic STK11 variants, particularly those associated with Peutz-Jeghers syndrome, there is no specific evidence that particular lifestyle modifications alter outcomes or reduce cancer risk associated with this genetic condition. While general healthy lifestyle principles-such as balanced nutrition, physical activity, and avoidance of tobacco-are beneficial recommendations for the broader population, they have not been shown in research to specifically mitigate the elevated cancer risks linked to STK11 variants. Regular medical surveillance and adherence to screening guidelines, as advised by healthcare professionals, remain the crucial components of clinical management for individuals with these genetic changes.
Supplement considerations
There is no conclusive evidence that specific dietary supplements can prevent cancer or alter the course of Peutz-Jeghers syndrome in individuals with STK11 variants. While some research explores the role of various nutrients in cancer prevention in the general population, these findings cannot be directly extrapolated to individuals with specific genetic predispositions. Individuals considering any supplements should always discuss this with their healthcare provider to ensure there are no potential interactions with existing medications or specific health risks.
Frequently asked questions
What is the STK11 gene?
The STK11 gene provides instructions for making an enzyme called serine/threonine kinase 11, which acts as a tumour suppressor. This enzyme helps control cell growth, division, and energy use, preventing uncontrolled cell proliferation.
What condition is most commonly associated with STK11 variants?
The condition most commonly associated with inherited pathogenic STK11 variants is Peutz-Jeghers syndrome. This syndrome is characterised by gastrointestinal polyps and an increased risk of developing various cancers.
How does STK11 act as a tumour suppressor?
STK11 acts as a tumour suppressor by regulating cell polarity, controlling cell energy metabolism, and promoting programmed cell death (apoptosis). These functions prevent cells from growing and dividing too rapidly or abnormally.
Is STK11 testing available in the UK?
Yes, STK11 gene testing is available in the UK through the NHS Genomic Medicine Service for individuals who meet specific clinical criteria. It is included on several NHS PanelApp panels related to cancer susceptibility and inherited conditions.
Can lifestyle changes prevent cancer in individuals with STK11 variants?
While a healthy lifestyle is generally beneficial, there is no conclusive evidence that specific lifestyle changes alone can prevent cancer in individuals with pathogenic STK11 variants. Regular medical surveillance and adherence to screening guidelines are crucial for managing associated risks.
Are somatic STK11 mutations different from inherited mutations?
Yes, somatic STK11 mutations are acquired during a person's lifetime and are present only in certain cells, such as in a tumour. Inherited (germline) mutations are present in nearly all cells of the body from birth and can be passed down through families.
References
- Hardie DG, Alessi DR. LKB1 and AMPK and the cancer-metabolism link - ten years after. BMC biology. 2013. PMID: 23587167
- Weissman SM, Weiss SM, Newlin AC. Genetic testing by cancer site: ovary. Cancer journal (Sudbury, Mass.). 2012. PMID: 22846732
- Vaahtomeri K, Mäkelä TP. Molecular mechanisms of tumor suppression by LKB1. FEBS letters. 2011. PMID: 21192934
- Wingo SN, Gallardo TD, Akbay EA. Somatic LKB1 mutations promote cervical cancer progression. PloS one. 2009. PMID: 19340305
- Zhuang ZG, Di GH, Shen ZZ. Enhanced expression of LKB1 in breast cancer cells attenuates angiogenesis, invasion, and metastatic potential. Molecular cancer research : MCR. 2006. PMID: 17114342
- Hemminki A, Markie D, Tomlinson I. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998. PMID: 9428765
- Adam MP, Bick S, Mirzaa GM. Peutz-Jeghers Syndrome. 1993. PMID: 20301443