{"entity":{"id":"stk11","kind":"target","name":"STK11","aka":["serine/threonine kinase 11","Serine/threonine-protein kinase STK11","LKB1"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11389","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11389"},{"label":"UniProt Q15831","url":"https://www.uniprot.org/uniprotkb/Q15831/entry"},{"label":"NCBI Gene 6794","url":"https://www.ncbi.nlm.nih.gov/gene/6794"},{"label":"Ensembl ENSG00000118046","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118046"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen","stk11-keap1-loss"],"cancers":["lung-cancer","ovarian","cervical","breast-cancer","prostate","pancreatic","anal","thyroid","gallbladder","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["keap1-nrf2","lipid-metabolism-cancer"],"terms":["stk11-keap1"],"trials":["nct05276726","nct05445843","nct05887492","nct06008093"],"people":[],"bottlenecks":[],"keyPapers":["paper-pandey-gallbladder-elf3-nat-commun-2020","paper-giraldo-gallbladder-msk-impact-ccr-2022","paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","paper-kras-nsclc-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 17 therapies; IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 11 cohorts; CIViC holds 23 clinical evidence items on its variants; UniProt keyword \"DNA damage\". Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Peutz-Jeghers Syndrome.","Lung cancer: inactivated in 13 to 18% of adenocarcinomas, 22.1% of patients selected for PD-(L)1 blockade and only 1.0% of squamous tumours (cBioPortal). It makes the tumour immune-poor, with low PD-L1 and few infiltrating lymphocytes (Skoulidis 2015), and it predicts worse progression-free and overall survival on checkpoint blockade, with hazard ratios around 2, but only in KRAS-mutant tumours (Ricciuti 2022, Skoulidis 2018). In the randomised trials of pembrolizumab with and without chemotherapy, STK11 status did not change the benefit (Mok 2023, Garassino 2023), so it is prognostic information rather than a reason to withhold treatment."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"STK11","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11389","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11389","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q15831","url":"https://www.uniprot.org/uniprotkb/Q15831/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene STK11","url":"https://civicdb.org/features/5534","note":"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)"},{"label":"Open Targets ENSG00000118046","url":"https://platform.opentargets.org/target/ENSG00000118046/associations","note":"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)"},{"label":"IntOGen STK11","url":"https://www.intogen.org/search?gene=STK11","note":"driver in 14 cohorts (Act 3, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt Q15831","url":"https://www.uniprot.org/uniprotkb/Q15831/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene STK11","url":"https://civicdb.org/features/5534","note":"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)"},{"label":"IntOGen STK11","url":"https://www.intogen.org/search?gene=STK11","note":"driver in 14 cohorts (Act 3, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas STK11 tissue","url":"https://www.proteinatlas.org/ENSG00000118046-STK11/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000118046 associations","url":"https://platform.opentargets.org/target/ENSG00000118046/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11389","ensembl":"ENSG00000118046","uniprot":"Q15831","entrez":"6794","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9425897/","biology":"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).","whereFound":["Lung cancer: Open Targets association 0.75 with lung cancer (MONDO_0008903)","Ovarian cancer: Open Targets association 0.64 with ovarian cancer (MONDO_0008170)","Cervical cancer: Open Targets association 0.61 with cervical cancer (MONDO_0002974); IntOGen driver in 3 cohorts (CEAD, CESC)","Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Prostate cancer: CIViC evidence names this disease","Pancreatic ductal adenocarcinoma: CIViC evidence names this disease","Gallbladder cancer: mutation about 9%","Non-small-cell lung cancer: inactivating mutation 13-18%"],"targetClass":"kinase","prevalence":[{"cancerId":"gallbladder","pct":9,"measure":"Mutation","source":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022","note":"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)."},{"cancerId":"nsclc","pct":"13-18","measure":"Inactivating mutation","source":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism","note":"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)."}]},"route":"/targets/stk11/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"biomarker":[{"id":"stk11-keap1-loss","kind":"biomarker","name":"STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma","route":"/biomarkers/stk11-keap1-loss/"}],"cancer":[{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"pathway":[{"id":"keap1-nrf2","kind":"pathway","name":"KEAP1-NRF2 antioxidant pathway","route":"/pathways/keap1-nrf2/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"}],"term":[{"id":"familial-pancreatic-cancer","kind":"term","name":"Familial pancreatic cancer and inherited risk (who qualifies for surveillance)","route":"/terms/familial-pancreatic-cancer/"},{"id":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","route":"/terms/stk11-keap1/"}],"trial":[{"id":"nct05276726","kind":"trial","name":"A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1","route":"/trials/nct05276726/"},{"id":"nct06008093","kind":"trial","name":"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","route":"/trials/nct06008093/"},{"id":"nct05445843","kind":"trial","name":"Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.","route":"/trials/nct05445843/"},{"id":"nct05887492","kind":"trial","name":"Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors","route":"/trials/nct05887492/"}],"paper":[{"id":"paper-keynote-042-tmb-mutations-ann-oncol-2023","kind":"paper","name":"Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042","route":"/key-papers/paper-keynote-042-tmb-mutations-ann-oncol-2023/"},{"id":"paper-keynote-189-407-tmb-jtocrr-2023","kind":"paper","name":"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","route":"/key-papers/paper-keynote-189-407-tmb-jtocrr-2023/"},{"id":"paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","kind":"paper","name":"Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities","route":"/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/"},{"id":"paper-giraldo-gallbladder-msk-impact-ccr-2022","kind":"paper","name":"Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention","route":"/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/"},{"id":"paper-tcga-lung-adenocarcinoma-nature-2014","kind":"paper","name":"Comprehensive molecular profiling of lung adenocarcinoma","route":"/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/"},{"id":"paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","kind":"paper","name":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","route":"/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/"},{"id":"paper-arbour-kras-co-mutation-outcomes-ccr-2018","kind":"paper","name":"Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer","route":"/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/"},{"id":"paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","kind":"paper","name":"Genomic landscape of lung adenocarcinoma in East Asians","route":"/key-papers/paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020/"},{"id":"paper-pandey-gallbladder-elf3-nat-commun-2020","kind":"paper","name":"Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate","route":"/key-papers/paper-pandey-gallbladder-elf3-nat-commun-2020/"},{"id":"paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","kind":"paper","name":"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","route":"/key-papers/paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018/"},{"id":"paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","kind":"paper","name":"Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies","route":"/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/"},{"id":"paper-kras-nsclc-cancer-discov-2018","kind":"paper","name":"STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma","route":"/key-papers/paper-kras-nsclc-cancer-discov-2018/"},{"id":"paper-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","route":"/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/"}]}}