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STK11 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Tumour suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53.
CIViC holds 23 clinical evidence items and 0 assertions across 8 variants, naming Sirolimus, MEK Inhibitor CI-1040, Everolimus and Cisplatin/Pembrolizumab/Pemetrexed Regimen and others. Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes genetic literature 0.75, affected pathway 0.96, literature 1.00, genetic association 0.72, somatic mutation 0.96, animal model 0.77). IntOGen calls it a driver in 14 cohorts (3 activating, 11 loss-of-function), covering Anal Squamous Cell Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Cholangiocarcinoma, Lung Adenocarcinoma, Non-Small Cell Lung Cancer and others.
In plain words · STK11 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
STK11 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Tumour suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response.
No product in this corpus aims at STK11 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA STK11: RNA low tissue specificity; high antibody staining in 1 normal tissue. Distribution: 9 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Biliary tract cancer (all types), Lung cancer (all types), Ovarian cancer, Cervical cancer, Breast cancer (all types), Prostate cancer, Pancreatic ductal adenocarcinoma and more); Open Targets associates it with 7 specific cancer types at or above 0.5 (Peutz-Jeghers syndrome, familial pancreatic carcinoma, lung adenocarcinoma, melanoma, cutaneous malignant, susceptibility to, 1, testicular germ cell tumor, hereditary neoplastic syndrome and more). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q15831; CIViC gene STK11; IntOGen STK11; Human Protein Atlas STK11 tissue; Open Targets ENSG00000118046 associations
First described 1998. Earliest sequence paper UniProt cites for the protein: Jenne D.E. et al, Nat. Genet, 1998, "Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase". Source.
Sources: HGNC HGNC:11389 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q15831 (protein name, function text, keywords and locations (REST API)); CIViC gene STK11 (23 evidence items, 0 assertions, 8 variants; diseases: Lung Non-small Cell Carcinoma, Peutz-Jeghers Syndrome, Breast Cancer, Lung Adenocarcinoma, Prostate Cancer and 2 more (GraphQL API, CC0)); Open Targets ENSG00000118046 (association with cancer (MONDO_0004992) 0.87; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.74, colorectal cancer 0.53, gastric cancer 0.53, ovarian cancer 0.64, cervical cancer 0.61, melanoma 0.63 (GraphQL API, CC0)); IntOGen STK11 (driver in 14 cohorts (Act 3, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Tumour suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signalling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal centre in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarisation by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Location: Nucleus; Cytoplasm; Membrane; Mitochondrion (UniProt). Locus 19p13.3 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Breast, Bronchus, Caudate, Cerebellum, Cerebral cortex.
No cancer stained high; medium in breast cancer, carcinoid, cervical cancer, colorectal cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 13-18% | Inactivating mutation | cBioPortal: 450 of 2,653, 17.0%, in luad_mskcc_2023_met_organotropism; 157 of 915, 17.2%, in lung_msk_2017; 75 of 566, 13.3%, in luad_tcga_pan_can_atlas_2018; 40 of 230, 17.4%, in luad_tcga_pub; 20 of 110, 18.2%, in luad_cptac_2020; 222 of 2,621, 8.5%, in nsclc_ctdx_msk_2022 (mixed histology); 11 of 302, 3.6%, in luad_oncosg_2020; 5 of 232, 2.2%, in lung_nci_2022. In the immunotherapy-treated cohort the rate is higher, 53 of 240, 22.1%, in nsclc_pd1_msk_2018 (cBioPortal); deleterious STK11 mutations were found in 260 of 1,261, 20.6%, of a two-centre lung adenocarcinoma cohort (Ricciuti 2022). | cBioPortal (TCGA) |
| Gallbladder cancer | 9% | Mutation | Mutation in 22 of 244 samples, 9.0%, in cBioPortal gbc_mskcc_2022; a significantly mutated gene (Pandey 2020) independently associated with reduced survival in metastatic disease (Giraldo 2022). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.
This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
It corrected a widely repeated simplification. An STK11 or KEAP1 mutation is not by itself a reason to expect immunotherapy to fail; it is a reason to expect it in a KRAS-mutant tumour, which is how the result should be read on a report.
It shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.
A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.
It turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.
It separated the prognostic co-mutation, KEAP1, from the predictive one, STK11, in a disease where the two are often quoted together, and it is the reason KEAP1 status is worth reading off a report even though no treatment depends on it.
Query for this target: (TITLE:"STK11" OR ABSTRACT:"STK11" OR TITLE:"serine/threonine kinase 11" OR ABSTRACT:"serine/threonine kinase 11" OR TITLE:"Serine/threonine-protein kinase STK11" OR ABSTRACT:"Serine/threonine-protein kinase STK11" OR TITLE:"LKB1" OR ABSTRACT:"LKB1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about STK11, not a curated reading list.
Shares A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1, Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS, STK11 / KEAP1 co-mutations.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer, KEAP1-NRF2 antioxidant pathway, Cervical cancer.
Shares Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities, Comprehensive molecular profiling of lung adenocarcinoma, Thyroid cancer, IntOGen.
Shares The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer, CIViC, IntOGen, Ovarian cancer.
Shares The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer, Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer, Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies, Lung cancer (all types).
Shares The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer, Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer, STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma, Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities.
Shares Thyroid cancer, CIViC, IntOGen, Lung cancer (all types).
Shares Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042, Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing.