STK11
serine/threonine kinase 11
Basic information
Region (hg38): 19:1177557-1228431
Links
Phenotypes
GenCC
Source:
- Peutz-Jeghers syndrome (Strong), mode of inheritance: AD
- Peutz-Jeghers syndrome (Strong), mode of inheritance: AD
- Peutz-Jeghers syndrome (Supportive), mode of inheritance: AD
- familial pancreatic carcinoma (Definitive), mode of inheritance: AD
- Peutz-Jeghers syndrome (Definitive), mode of inheritance: AD
- familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
- Peutz-Jeghers syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Peutz-Jeghers syndrome | AD | Gastrointestinal; Oncologic | Routine surgical/endoscopic procedures can decrease the need of emergent procedures for sudden and severe sequelae (eg, intussusception); Surveillance for and early treatment of a variety of common malignancies (individuals may be at increased risk of a number of types of epithelial malignancies, including breast, cervical adenoma malignum, colorectal, gastric, ovarian, pancreatic cancers, sex cord tumors with annular tubules, and testicular Sertoli cell tumors) can be beneficial | Dermatologic; Gastrointestinal; Oncologic | 15399020; 14214503; 14279723; 5466889; 990720; 7436458; 3943856; 3697923; 3587280; 3181678; 2599445; 1986290; 7776109; 7802138; 9850045; 9428765; 9425897; 10408777; 10689645; 10874301; 11389158; 12044140; 15121768; 15200509; 15863673; 15617552; 20581245; 20301443 |
ClinVar
This is a list of variants' phenotypes submitted to
- Peutz-Jeghers syndrome (1725 variants)
- Hereditary cancer-predisposing syndrome (1369 variants)
- not provided (442 variants)
- not specified (336 variants)
- Melanoma, cutaneous malignant, susceptibility to, 1 (65 variants)
- Breast and/or ovarian cancer (51 variants)
- Malignant tumor of breast (35 variants)
- Carcinoma of pancreas (8 variants)
- STK11-related condition (8 variants)
- Squamous cell lung carcinoma (7 variants)
- Familial ovarian cancer (6 variants)
- Neoplasm (5 variants)
- Breast carcinoma (4 variants)
- Carcinoma of pancreas;Peutz-Jeghers syndrome;Malignant tumor of testis (4 variants)
- Carcinoma of colon (4 variants)
- Germ cell tumor of testis;Melanoma, cutaneous malignant, susceptibility to, 1;Carcinoma of pancreas;Peutz-Jeghers syndrome (4 variants)
- Lung adenocarcinoma (3 variants)
- Ovarian cancer (3 variants)
- Hereditary breast ovarian cancer syndrome (3 variants)
- Germ cell tumor of testis;Carcinoma of pancreas;Peutz-Jeghers syndrome;Melanoma, cutaneous malignant, susceptibility to, 1 (3 variants)
- Hereditary cancer (3 variants)
- Generalized juvenile polyposis/juvenile polyposis coli (3 variants)
- Squamous cell carcinoma (2 variants)
- Inborn genetic diseases (2 variants)
- Carcinoma of pancreas;Malignant tumor of testis;Peutz-Jeghers syndrome (2 variants)
- Intestinal polyposis (1 variants)
- Embryonal rhabdomyosarcoma (1 variants)
- B Lymphoblastic Leukemia/Lymphoma, Not Otherwise Specified (1 variants)
- Endometrial carcinoma (1 variants)
- Germ cell tumor of testis;Melanoma, cutaneous malignant, susceptibility to, 1;Peutz-Jeghers syndrome;Carcinoma of pancreas (1 variants)
- Periorbital hyperpigmentation;Intestinal polyposis (1 variants)
- Melanoma, cutaneous malignant, susceptibility to, 1;Carcinoma of pancreas;Peutz-Jeghers syndrome;Germ cell tumor of testis (1 variants)
- Gastric cancer (1 variants)
- Neoplasm of the pancreas (1 variants)
- Bile duct cancer (1 variants)
- Melanoma (1 variants)
- Malignant neoplasm of brain (1 variants)
- Malignant tumor of testis;Carcinoma of pancreas;Peutz-Jeghers syndrome (1 variants)
- Lip and oral cavity carcinoma (1 variants)
- Melanoma, cutaneous malignant, susceptibility to, 1;Germ cell tumor of testis;Carcinoma of pancreas;Peutz-Jeghers syndrome (1 variants)
- Breast cancer, susceptibility to (1 variants)
- Malignant tumor of testis (1 variants)
- Arthrogryposis, distal, with impaired proprioception and touch (1 variants)
- Colon cancer (1 variants)
- Marfanoid habitus and intellectual disability (1 variants)
- Hepatoblastoma (1 variants)
- Familial adenomatous polyposis 2 (1 variants)
- Familial adenomatous polyposis 1 (1 variants)
- Multiple endocrine neoplasia, type 1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the STK11 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 439 | 445 | ||||
| missense | 12 | 18 | 807 | 842 | ||
| nonsense | 44 | 51 | ||||
| start loss | 3 | |||||
| frameshift | 115 | 13 | 10 | 138 | ||
| inframe indel | 25 | 30 | ||||
| splice donor/acceptor (+/-2bp) | 27 | 18 | 51 | |||
| splice region ? | 2 | 1 | 43 | 56 | 5 | 107 |
| non coding ? | 77 | 290 | 49 | 417 | ||
| Total | 203 | 55 | 934 | 734 | 51 |
Highest pathogenic variant AF is 0.00000657
Variants in STK11
This is a list of pathogenic ClinVar variants found in the STK11 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| STK11 | protein_coding | protein_coding | ENST00000326873 | 9 | 39023 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.993 | 0.00660 | 120835 | 0 | 1 | 120836 | 0.00000414 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.60 | 203 | 278 | 0.730 | 0.0000176 | 2817 |
| Missense in Polyphen | 36 | 109.45 | 0.32892 | 1226 | ||
| Synonymous | -2.90 | 167 | 126 | 1.33 | 0.00000921 | 822 |
| Loss of Function | 3.87 | 1 | 19.4 | 0.0516 | 8.21e-7 | 231 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000918 | 0.00000918 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Tumor 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 signaling 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 center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.;
- Disease
- DISEASE: Peutz-Jeghers syndrome (PJS) [MIM:175200]: An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. {ECO:0000269|PubMed:10408777, ECO:0000269|PubMed:12372054, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:21411391, ECO:0000269|PubMed:9425897, ECO:0000269|PubMed:9428765, ECO:0000269|PubMed:9760200, ECO:0000269|PubMed:9837816}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. {ECO:0000269|PubMed:9605748, ECO:0000269|PubMed:9887330}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Note=Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans- differentiate into squamous cell carcinoma. Also able to promotes lung cancer metastasis, via both cancer-cell autonomous and non- cancer-cell autonomous mechanisms.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Tight junction - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;WNT-Ncore;EGF-Ncore;AMP-activated Protein Kinase (AMPK) Signaling;Integrated Breast Cancer Pathway;Polycystic Kidney Disease Pathway;mir-124 predicted interactions with cell cycle and differentiation;ATM Signaling Network in Development and Disease;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;AMPK inhibits chREBP transcriptional activation activity;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Metabolism;TGF_beta_Receptor;EGFR1;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Integration of energy metabolism;LKB1 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.307
Intolerance Scores
- loftool
- 0.112
- rvis_EVS
- -0.54
- rvis_percentile_EVS
- 20.54
Haploinsufficiency Scores
- pHI
- 0.531
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.629
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Stk11
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; digestive/alimentary phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- stk11
- Affected structure
- intestinal epithelium
- Phenotype tag
- abnormal
- Phenotype quality
- flattened
Gene ontology
- Biological process
- regulation of cell growth;tissue homeostasis;vasculature development;protein phosphorylation;protein dephosphorylation;autophagy;cellular response to DNA damage stimulus;cell cycle arrest;spermatogenesis;axonogenesis;negative regulation of cell population proliferation;response to ionizing radiation;positive regulation of autophagy;establishment of cell polarity;negative regulation of cell growth;positive regulation of transforming growth factor beta receptor signaling pathway;activation of protein kinase activity;glucose homeostasis;anoikis;positive thymic T cell selection;protein autophosphorylation;regulation of dendrite morphogenesis;positive regulation of axonogenesis;T cell receptor signaling pathway;Golgi localization;regulation of protein kinase B signaling;canonical Wnt signaling pathway;negative regulation of epithelial cell proliferation involved in prostate gland development;cellular response to UV-B;intrinsic apoptotic signaling pathway by p53 class mediator;negative regulation of canonical Wnt signaling pathway;dendrite extension;negative regulation of cold-induced thermogenesis;positive regulation of protein localization to nucleus;regulation of signal transduction by p53 class mediator;negative regulation of TORC1 signaling
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;membrane;extracellular exosome
- Molecular function
- magnesium ion binding;p53 binding;protein serine/threonine kinase activity;protein binding;ATP binding;LRR domain binding;protein kinase activator activity