STK11

Summary

STK11 (serine/threonine kinase 11, HGNC:11389) is a protein-coding gene on chromosome 19p13.3, encoding Serine/threonine-protein kinase STK11 (Q15831). 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. In precision oncology, STK11 Mutation confers sensitivity to Vistusertib in Lung Non-small Cell Carcinoma (CIViC Level B); 10 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 18.9% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers.

Source: NCBI Gene 6794 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Peutz-Jeghers syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 2,818 total — 310 pathogenic, 80 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 11 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• Cancer dependency (DepMap): dependent in 18.9% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000455

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11389
Approved symbol	STK11
Name	serine/threonine kinase 11
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PJS, LKB1
Ensembl gene	ENSG00000118046
Ensembl biotype	protein_coding
OMIM	602216
Entrez	6794

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000326873, ENST00000585465, ENST00000585748, ENST00000585851, ENST00000586358, ENST00000589152, ENST00000591133, ENST00000593219, ENST00000652231, ENST00000714318, ENST00000714319, ENST00000714320, ENST00000714321, ENST00000714322, ENST00000714323, ENST00000916852, ENST00000916853, ENST00000942781, ENST00000942782, ENST00000942783

RefSeq mRNA: 2 — MANE Select: NM_000455 NM_000455, NM_001407255

CCDS: CCDS45896

Canonical transcript exons

ENST00000326873 — 10 exons

Exon	Start	End
ENSE00002739759	1219324	1219413
ENSE00004013651	1226454	1226663
ENSE00004013652	1222985	1223172
ENSE00004013654	1221213	1221340
ENSE00004013655	1218417	1218500
ENSE00004013656	1220373	1220505
ENSE00004013657	1220581	1220717
ENSE00004013658	1221949	1222006
ENSE00004013659	1227593	1228431
ENSE00004023558	1205778	1207203

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 97.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6234 / max 197.3485, expressed in 1791 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172896	13.2149	1791
172897	0.2612	81
172898	0.0489	10
172900	0.0314	6
172899	0.0274	4
172903	0.0174	6
172901	0.0164	4
172902	0.0057	2

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.81	gold quality
right testis	UBERON:0004534	97.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.71	gold quality
gastrocnemius	UBERON:0001388	95.57	gold quality
testis	UBERON:0000473	95.14	gold quality
granulocyte	CL:0000094	95.08	gold quality
muscle of leg	UBERON:0001383	94.99	gold quality
stromal cell of endometrium	CL:0002255	94.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.44	gold quality
tendon of biceps brachii	UBERON:0008188	94.42	gold quality
mucosa of transverse colon	UBERON:0004991	94.24	gold quality
cerebellar hemisphere	UBERON:0002245	94.03	gold quality
cerebellar cortex	UBERON:0002129	93.84	gold quality
apex of heart	UBERON:0002098	93.68	gold quality
left adrenal gland cortex	UBERON:0035825	93.01	gold quality
transverse colon	UBERON:0001157	92.91	gold quality
body of stomach	UBERON:0001161	92.84	gold quality
endothelial cell	CL:0000115	92.69	gold quality
right atrium auricular region	UBERON:0006631	92.65	gold quality
lower esophagus mucosa	UBERON:0035834	92.65	gold quality
left adrenal gland	UBERON:0001234	92.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.57	gold quality
skin of leg	UBERON:0001511	92.56	gold quality
endocervix	UBERON:0000458	92.53	gold quality
right uterine tube	UBERON:0001302	92.47	gold quality
left ovary	UBERON:0002119	92.46	gold quality
metanephros cortex	UBERON:0010533	92.36	gold quality
right adrenal gland cortex	UBERON:0035827	92.34	gold quality
right adrenal gland	UBERON:0001233	92.33	gold quality
sural nerve	UBERON:0015488	92.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.88

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CPS1	Repression

Upstream regulators (CollecTRI, top): CREBZF, ESR1, FOXO3, HNF4A, NFYA, NFYB, NKX2-1, NR1H4, SP1, STAT3, STAT5A, TP53, TXK

miRNA regulators (miRDB)

32 targeting STK11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-4474-5P	94.23	67.95	568

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 18.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Various fungi stimulated antimicrobial peptides through at least two different pathways requiring Relish and/or Dif. (PMID:14985331)
• Dif and Dorsal control crucial aspects of the cellular immune response (PMID:17060622)
• Molecular modeling was used to compare the tertiary structure of Dif with two other Drosophila proteins. (PMID:17785540)
• Data show that the DIF and Relish complex is detectable in whole animal extracts, suggesting that this heterodimer may function in vivo to increase the spectrum and level of antimicrobial peptide production in response to different infections. (PMID:20679214)
• DIF factor seems to be involved in the response to fungal infection after a mild cold stress and in the resistance to heat. DIF seems to have no role in the increased longevity of non-infected flies and resistance to a severe cold shock. (PMID:22791143)
• Fasting increases survival to cold in dif mutant Drosophila melanogaster. (PMID:25663303)
• These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity. (PMID:27974298)
• Study shows that Drosophila miR-317 only targets Dif-Rc, but not Dif-Ra/b/d, implying that miRNAs can regulate different isoforms of an alternative splicing gene to fine tune immune responses and maintain homeostasis in post-transcriptional level. During Gram-positive bacterial infection, the overexpressed miR-317 flies have poor survival outcome suggesting that the miR-317 might play a key role in Drosophila survival. (PMID:30708026)
• Bacterial recognition by PGRP-SA and downstream signalling by Toll/DIF sustain commensal gut bacteria in Drosophila. (PMID:35007276)
• Interaction of lncRNA-CR33942 with Dif/Dorsal Facilitates Antimicrobial Peptide Transcriptions and Enhances Drosophila Toll Immune Responses. (PMID:35379744)
• This paper describes the identification and characterization of the first binding partner of LKB1; the SWI/SNF chromatin remodeling protein Brg1. (PMID:11445556)
• mutation screening at the RNA level in Peutz-Jeghers syndrome reveals complex splicing abnormalities and a novel mRNA isoform (STK11 c.597(insertion mark)598insIVS4 (PMID:11668633)
• STK11/LKB1 gene in IPMNs (intraductal papillary-mucinous neoplasms of the pancreas) with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS (Peutz-Jeghers Syndrome) and a somatic mutation in 1 of the 20 sporadic IPMNs. (PMID:11733352)
• LKB1 is phosphorylated at Ser(431), Ser(31), Ser(325) and Thr(366) (PMID:11853558)
• Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. (PMID:12097271)
• This reports for the first time the presence of frequent LKB1 inactivating mutations in human lung cancer. (PMID:12097271)
• polyps arising in the Lkb1+/- mice were found to be hamartomas that were histologically indistinguishable from polyps resected from PJS patients, indicating that Lkb1+/- mice model human PJS polyposis (PMID:12218179)
• These observations provide the first link between ATM and LKB1 and suggest that ATM could regulate LKB1 (PMID:12234250)
• Results show that Cdc37 and heat shock protein 90 bind specifically to the kinase domain of LKB1. (PMID:12489981)
• mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix (PMID:12533684)
• LKB1/STK11 variants in a group of Peutz-Jeghers syndrome Italian patients lack serine/threonine kinase activity, in contrast to wild type LKB1/STK11, and are unable to suppress the growth of melanoma G361 cells in vitro. (PMID:12552571)
• identification and characterization of an LKB1-specific adaptor protein and substrate, STRAD (STe20 Related ADaptor); results imply that STRAD plays a key role in regulating the tumour suppressor activities of LKB1 (PMID:12805220)
• LKB1 kinase, which is associated with Peutz-Jeghers cancer-susceptibility syndrome, phosphorylates and activates AMPK in vitro. (PMID:12847291)
• results show that LKB1 can direct the phosphorylation of the serine-threonine kinase PAR1A (PMID:12879020)
• LKB1 inactivation may play a role in the critical transition from premalignant to malignant tumor growth (PMID:12912948)
• LKB1-induced apoptosis is p53 independent but might be p73-mediated in pancreatic tumors (PMID:14511408)
• heteromeric complex containing the molecular chaperones Hsp90 and Cdc37/p50 interacts with the kinase domain of LKB1 (PMID:14668798)
• LKB1 functions as a master upstream protein kinase, regulating AMPK-related kinases as well as AMPK. (PMID:14976552)
• LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its kinase activity. (PMID:14985505)
• our results reveal that several important factors contribute to LKB1-mediated carcinogenesis in LADs, confirming previous observations and identifying new putative pathways that should help to elucidate the biological role of LKB1. (PMID:15077168)
• the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively (PMID:15188174)
• LKB1, the gene mutated in Peutz-Jeghers syndrome (PJS), acts as a tumor suppressor by activating TSC2, the gene mutated in Tuberous sclerosis complex (PMID:15231735)
• Cases in which Peutz-Jegher Syndrome patients did not harbor mutation of STK11. (PMID:15287029)
• IGF-1 induces AMPK-alpha subunit phosphorylation via an ATM-dependent and LKB1-independent pathway (PMID:15485651)
• Mutations in LKB1 cause the inherited Peutz-Jeghers syndrome. (PMID:15561763)
• The unusual splicing defect of LKB1 associated with this Peutz-Jeghers syndrome-causing mutation uncovers differences in splice-site recognition between the major and minor pre-mRNA splicing pathways (PMID:15608654)
• report of a novel truncating-type germline mutation of the STK11 gene in a Peutz-Jeghers syndrome patient with gastric cancer (PMID:15617552)
• LKB1 mutants, in Peutz-Jeghers syndrome, fail to activate GSK-3beta, preventing it from inhibiting Wnt signaling. (PMID:15731909)
• promoter element sequence changes in STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome (PMID:15774015)
• LKB1 is crucial for the regulation of cell polarity (PMID:15800014)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk11	ENSDARG00000046074
mus_musculus	Stk11	ENSMUSG00000003068
rattus_norvegicus	Stk11	ENSRNOG00000014287
drosophila_melanogaster	Lkb1	FBGN0038167
caenorhabditis_elegans		WBGENE00003919

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Serine/threonine-protein kinase STK11 — Q15831 (reviewed: Q15831)

Alternative names: Liver kinase B1, Renal carcinoma antigen NY-REN-19

All UniProt accessions (12): Q15831, A0A087WT72, A0A0S2Z4D1, A0A1B0GUW2, A0AAQ5BHS0, A0AAQ5BHS4, A0AAQ5BHU8, A0AAQ5BHW9, A0AAQ5BHX7, A0AAQ5BHX9, K7EMR0, K7EQN8

UniProt curated annotations — full annotation on UniProt →

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. 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. Has a role in spermiogenesis.

Subunit / interactions. Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, STK11IP and WDR6. Interacts with NR4A1. Interacts with NISCH; this interaction may increase STK11 activity. Interacts with PTEN; leading to PTEN phosphorylation. Interacts with SIRT1; the interaction deacetylates STK11. Interacts with CDKN1A.

Subcellular location. Nucleus. Cytoplasm. Membrane. Mitochondrion Nucleus.

Tissue specificity. Ubiquitously expressed. Strongest expression in testis and fetal liver.

Post-translational modifications. Phosphorylated by ATM at Thr-363 following ionizing radiation (IR). Phosphorylation at Ser-428 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-428 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2. Phosphorylation by PKC/PRKCZ at Ser-399 in isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export of STK11 and activation of AMPK. UV radiation-induced phosphorylation at Thr-363 mediates CDKN1A degradation. Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The gene represented in this entry may be involved in disease pathogenesis. 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 promote lung cancer metastasis, via both cancer-cell autonomous and non-cancer-cell autonomous mechanisms.

Activity regulation. Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15831-1	1, LKB1(L)	yes
Q15831-2	2, LKB1(S)

RefSeq proteins (2): NP_000446, NP_001394184 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR039154	LKB1_c	Domain

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (123 total): sequence variant 50, modified residue 18, helix 15, mutagenesis site 12, strand 10, turn 4, region of interest 3, binding site 2, lipid moiety-binding region 2, compositionally biased region 2, chain 1, propeptide 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2WTK	X-RAY DIFFRACTION	2.65
8VSU	ELECTRON MICROSCOPY	2.86
4ZDR	X-RAY DIFFRACTION	2.9
5WXN	X-RAY DIFFRACTION	2.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15831-F1	79.27	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 176 (proton acceptor)

Ligand- & substrate-binding residues (2): 78; 55–63

Post-translational modifications (20): 31, 44, 399, 48, 96, 97, 189, 296, 311, 325, 336, 363, 401, 416, 423, 428, 430, 431, 418, 430

Mutagenesis-validated functional residues (12):

Position	Phenotype
44	no effect on kinase activity.
48	no effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with sirt1
48	enhanced phosphorylation at thr-336 and ser-428, enhanced cytoplasmic localization and increased kinase activity.
74	impaired formation of a heterotrimeric complex with strada and cab39; when associated with a-204.
78	loss of kinase activity, leading to greatly reduced autophosphorylation.
78	loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant.
96	no effect on kinase activity.
97	no effect on kinase activity.
189	reduced phosphorylation.
194	loss of kinase activity.
204	no effect. impaired formation of a heterotrimeric complex with strada and cab39; when associated with a-74.
428	no effect on kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-163680	AMPK inhibits chREBP transcriptional activation activity
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-9614657	FOXO-mediated transcription of cell death genes
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-165159	MTOR signalling
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9614085	FOXO-mediated transcription

MSigDB gene sets: 493 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_AUTOPHAGY, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_VESICLE_LOCALIZATION, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_THYMIC_T_CELL_SELECTION, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS

GO Biological Process (44): regulation of cell growth (GO:0001558), tissue homeostasis (GO:0001894), vasculature development (GO:0001944), protein phosphorylation (GO:0006468), protein dephosphorylation (GO:0006470), autophagy (GO:0006914), DNA damage response (GO:0006974), signal transduction (GO:0007165), spermatogenesis (GO:0007283), axonogenesis (GO:0007409), negative regulation of cell population proliferation (GO:0008285), response to ionizing radiation (GO:0010212), positive regulation of autophagy (GO:0010508), peptidyl-threonine phosphorylation (GO:0018107), establishment of cell polarity (GO:0030010), regulation of Wnt signaling pathway (GO:0030111), negative regulation of cell growth (GO:0030308), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), activation of protein kinase activity (GO:0032147), protein localization to nucleus (GO:0034504), glucose homeostasis (GO:0042593), anoikis (GO:0043276), positive thymic T cell selection (GO:0045059), protein autophosphorylation (GO:0046777), regulation of dendrite morphogenesis (GO:0048814), positive regulation of axonogenesis (GO:0050772), T cell receptor signaling pathway (GO:0050852), Golgi localization (GO:0051645), regulation of cell cycle (GO:0051726), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), epithelial cell proliferation involved in prostate gland development (GO:0060767), negative regulation of epithelial cell proliferation involved in prostate gland development (GO:0060770), G1 to G0 transition (GO:0070314), cellular response to UV-B (GO:0071493), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), negative regulation of canonical Wnt signaling pathway (GO:0090090), dendrite extension (GO:0097484), negative regulation of cold-induced thermogenesis (GO:0120163), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of vesicle transport along microtubule (GO:1901610)

GO Molecular Function (13): magnesium ion binding (GO:0000287), p53 binding (GO:0002039), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), LRR domain binding (GO:0030275), protein kinase activator activity (GO:0030295), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), cytosol (GO:0005829), cilium (GO:0005929), membrane (GO:0016020), extracellular exosome (GO:0070062), intracellular protein-containing complex (GO:0140535), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Generic Transcription Pathway	2
Integration of energy metabolism	1
MTOR signalling	1
Regulation of TP53 Activity	1
FOXO-mediated transcription	1
Metabolism	1
Signal Transduction	1
RNA Polymerase II Transcription	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	3
cell growth	2
protein modification process	2
negative regulation of cellular process	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of growth	1
regulation of cellular component organization	1
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
system development	1
circulatory system development	1
phosphorylation	1
dephosphorylation	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
developmental process involved in reproduction	1
male gamete generation	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
cell population proliferation	1
regulation of cell population proliferation	1
response to radiation	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
protein phosphorylation	1
peptidyl-threonine modification	1
establishment or maintenance of cell polarity	1
regulation of signal transduction	1
Wnt signaling pathway	1

Protein interactions and networks

STRING

4480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK11	CAB39	Q9Y376	999
STK11	STRADA	Q7RTN6	999
STK11	AXIN1	O15169	991
STK11	PTEN	P60484	971
STK11	CAB39L	Q9H9S4	963
STK11	STK11IP	Q8N1F8	878
STK11	KRAS	P01116	872
STK11	TP53	P04637	853
STK11	ATM	Q13315	846
STK11	TSC2	P49815	845
STK11	PALB2	Q86YC2	843
STK11	SMAD4	Q13485	840
STK11	STRADB	Q9C0K7	839
STK11	BRCA2	P51587	831
STK11	PIK3CA	P42336	817

IntAct

200 interactions, top by confidence:

A	B	Type	Score
STRADA	STK11	psi-mi:“MI:0915”(physical association)	0.960
STK11	STRADA	psi-mi:“MI:0217”(phosphorylation reaction)	0.960
STRADA	STK11	psi-mi:“MI:0403”(colocalization)	0.960
STK11	STRADA	psi-mi:“MI:0914”(association)	0.960
STK11	STRADA	psi-mi:“MI:2364”(proximity)	0.960
STK11	STRADA	psi-mi:“MI:0915”(physical association)	0.960
STK11	CAB39	psi-mi:“MI:0915”(physical association)	0.950
CAB39	STK11	psi-mi:“MI:0914”(association)	0.950
CAB39	STK11	psi-mi:“MI:0915”(physical association)	0.950
CAB39	STK11	psi-mi:“MI:2364”(proximity)	0.950
STRADB	STK11	psi-mi:“MI:0403”(colocalization)	0.920
STRADB	STK11	psi-mi:“MI:0915”(physical association)	0.920
STK11	STRADB	psi-mi:“MI:0915”(physical association)	0.920
STK11	FKBP5	psi-mi:“MI:0914”(association)	0.910
FKBP5	STK11	psi-mi:“MI:0915”(physical association)	0.910
STK11	CDC37	psi-mi:“MI:0915”(physical association)	0.850
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
HSP90AB1	STK11	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (466): STK11 (Biochemical Activity), SIRT1 (Affinity Capture-Western), STK11 (Affinity Capture-Western), ETV4 (Affinity Capture-Western), ETV4 (Two-hybrid), PRKAA1 (Two-hybrid), ETV4 (Biochemical Activity), PRKAA1 (Biochemical Activity), SPDEF (Two-hybrid), STK11 (Two-hybrid), CAB39 (Affinity Capture-MS), CCDC136 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZNK2, B1H3E1, D3ZSZ3, D4ABL6, D4AE59, E1BMN8, E2QWQ2, E9PV86, O54804, O54949, O70293, P15209, P24786, P33497, P43250, P43291, P43292, P46892, P49137, P49138, P85298, P97711, Q03351, Q0GGW5, Q15831, Q16644, Q3SYZ2, Q3UMW7, Q5N942, Q5XIS9, Q63604, Q66H84, Q6ZI44, Q75H77, Q75V57, Q7XKA8, Q7XQP4, Q7Y0B9, Q8BZ03, Q8CIW5

Diamond homologs: A2XFF4, A3B529, A6ZU08, A8WYE4, A8X0C4, B3DL84, B4J3F1, B4KYX8, B4LDJ6, B8BBT7, D4AE59, F1QGZ6, O08679, O14965, O22932, O55099, O59790, O70126, O88445, O88831, P25341, P25389, P32801, P38990, P43637, P50526, P54645, P59241, P92958, P97756, Q05512, Q0D4B2, Q0GGW5, Q0JI49, Q10SC8, Q12263, Q13131, Q14680, Q15831, Q16W24

SIGNOR signaling

69 interactions.

A	Effect	B	Mechanism
STK11	“up-regulates activity”	STK11	phosphorylation
STK11	“up-regulates activity”	MARK3	phosphorylation
STK11	“down-regulates activity”	STK11	phosphorylation
STK11	up-regulates	PRKAA2	phosphorylation
STK11	down-regulates	GSK3B
STK11	up-regulates	BRSK1	phosphorylation
STK11	up-regulates	BRSK2	phosphorylation
STK11	up-regulates	MARK1	phosphorylation
STK11	up-regulates	MARK2	phosphorylation
STK11	up-regulates	MARK4	phosphorylation
STK11	up-regulates	NUAK1	phosphorylation
STK11	up-regulates	NUAK2	phosphorylation
STK11	up-regulates	SIK1	phosphorylation
STK11	up-regulates	SIK2	phosphorylation
STK11	up-regulates	SIK3	phosphorylation
STK11	up-regulates	MELK	phosphorylation
STK11	up-regulates	TP53	phosphorylation
PRKCZ	“up-regulates activity”	STK11	phosphorylation
STK11	“down-regulates activity”	PTEN	phosphorylation
STK11	down-regulates	PAK1	phosphorylation
PRKCZ	up-regulates	STK11	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Energy dependent regulation of mTOR by LKB1-AMPK	5	18.9×	8e-04
MTOR signalling	7	17.9×	4e-05
RAF activation	5	16.1×	1e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	7	13.0×	2e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	11.9×	9e-05
TP53 Regulates Metabolic Genes	7	8.7×	1e-03
Transcriptional and post-translational regulation of MITF-M expression and activity	5	8.6×	7e-03
Programmed Cell Death	6	8.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	9	7.5×	1e-03
protein stabilization	14	7.5×	7e-06
protein folding	8	6.6×	5e-03
protein phosphorylation	12	6.5×	2e-04
positive regulation of apoptotic process	10	4.5×	9e-03
negative regulation of apoptotic process	13	3.6×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — ANSC, CEAD, CESC, CHOL, LUAD, NSCLC, WDTC.

Clinical variants and AI predictions

ClinVar

2818 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	310
Likely pathogenic	80
Uncertain significance	1041
Likely benign	578
Benign	102

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068630	NM_000455.5(STK11):c.734+1G>A	Pathogenic
1069286	NM_000455.5(STK11):c.889_890del (p.Arg297fs)	Pathogenic
1071855	NC_000019.9:g.(?1218406)(1218509_?)del	Pathogenic
1072061	NM_000455.5(STK11):c.788T>A (p.Leu263Ter)	Pathogenic
1072081	NC_000019.9:g.(?1221107)(1227749_?)del	Pathogenic
1073428	NM_000455.5(STK11):c.354_362del (p.Tyr118_Glu121delinsTer)	Pathogenic
1073558	NM_000455.5(STK11):c.640_653del (p.Gln214fs)	Pathogenic
1073837	NC_000019.9:g.(?1206913)(1207212_?)del	Pathogenic
1073838	NC_000019.9:g.(?1206903)(1207212_?)del	Pathogenic
1073839	NC_000019.9:g.(?1220366)(1220510_?)del	Pathogenic
1073840	NC_000019.9:g.(?1218406)(1219422_?)del	Pathogenic
1073934	NM_000455.5(STK11):c.332_333insG (p.Ile111fs)	Pathogenic
1075652	NM_000455.5(STK11):c.291-1G>C	Pathogenic
1075653	NM_000455.5(STK11):c.334C>T (p.Gln112Ter)	Pathogenic
1075654	NM_000455.5(STK11):c.464+1dup	Pathogenic
1075763	NM_000455.5(STK11):c.608_627del (p.Pro203fs)	Pathogenic
1075905	NC_000019.9:g.(?1206907)(1226652_?)del	Pathogenic
1076021	NM_000455.5(STK11):c.145dup (p.Tyr49fs)	Pathogenic
1184620	NM_000455.5(STK11):c.812del (p.Ser271fs)	Pathogenic
1297689	NM_000455.5(STK11):c.921-12G>A	Pathogenic
1342166	NM_000455.5(STK11):c.735-6A>G	Pathogenic
1350425	NC_000019.9:g.(?1206913)(1219422_?)del	Pathogenic
1359304	NM_000455.5(STK11):c.841_842dup (p.Leu282fs)	Pathogenic
1359873	NM_000455.5(STK11):c.464+1G>T	Pathogenic
1360522	NM_000455.5(STK11):c.597+2T>A	Pathogenic
1370818	NM_000455.5(STK11):c.290+1G>C	Pathogenic
1376969	NM_000455.5(STK11):c.583del (p.Leu195fs)	Pathogenic
1378041	NM_000455.5(STK11):c.19C>T (p.Gln7Ter)	Pathogenic
1379620	NM_000455.5(STK11):c.792_793insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGCTCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCACAGTGCTGTGATTACAGGCGTGAGCCACCGCGCCCGGCCTACAAGTTGTTT (p.Glu265delinsPhePhePhePhePhePheXaaXaaXaaXaaAlaLeuLeuThrSerTer)	Pathogenic
1404101	NM_000455.5(STK11):c.669_670del (p.Glu223fs)	Pathogenic

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1207200:AGAA:A	donor_gain	1.0000
19:1207201:GAA:G	donor_gain	1.0000
19:1207201:GAAG:G	donor_gain	1.0000
19:1207202:AA:A	donor_gain	1.0000
19:1207204:G:GG	donor_gain	1.0000
19:1218411:TCCCA:T	acceptor_loss	1.0000
19:1218412:CCCAG:C	acceptor_loss	1.0000
19:1218413:CCAG:C	acceptor_loss	1.0000
19:1218414:CAGGG:C	acceptor_loss	1.0000
19:1218415:A:AG	acceptor_gain	1.0000
19:1218415:A:AT	acceptor_loss	1.0000
19:1218415:AG:A	acceptor_gain	1.0000
19:1218415:AGG:A	acceptor_gain	1.0000
19:1218416:G:GG	acceptor_gain	1.0000
19:1218416:GG:G	acceptor_gain	1.0000
19:1218416:GGG:G	acceptor_gain	1.0000
19:1218416:GGGA:G	acceptor_gain	1.0000
19:1218416:GGGAA:G	acceptor_gain	1.0000
19:1220368:CGCA:C	acceptor_loss	1.0000
19:1220369:GCA:G	acceptor_loss	1.0000
19:1220370:CAGGT:C	acceptor_loss	1.0000
19:1220372:G:GT	acceptor_loss	1.0000
19:1220470:G:GA	donor_gain	1.0000
19:1220507:T:A	donor_loss	1.0000
19:1220714:CCCT:C	donor_gain	1.0000
19:1220715:CCT:C	donor_gain	1.0000
19:1220716:CT:C	donor_gain	1.0000
19:1220718:G:GG	donor_gain	1.0000
19:1220718:GT:G	donor_loss	1.0000
19:1220719:T:G	donor_loss	1.0000

AlphaMissense

2859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1207062:T:C	L50P	1.000
19:1207067:G:A	G52R	1.000
19:1207067:G:C	G52R	1.000
19:1207067:G:T	G52W	1.000
19:1207068:G:A	G52E	1.000
19:1207079:G:A	G56R	1.000
19:1207079:G:C	G56R	1.000
19:1207080:G:A	G56E	1.000
19:1207085:G:A	G58S	1.000
19:1207085:G:C	G58R	1.000
19:1207085:G:T	G58C	1.000
19:1207086:G:A	G58D	1.000
19:1207094:G:C	G61R	1.000
19:1207095:G:A	G61D	1.000
19:1207100:G:A	V63M	1.000
19:1207103:A:G	K64E	1.000
19:1207105:G:C	K64N	1.000
19:1207105:G:T	K64N	1.000
19:1207113:T:C	L67P	1.000
19:1207134:G:C	R74T	1.000
19:1207134:G:T	R74M	1.000
19:1207135:G:C	R74S	1.000
19:1207135:G:T	R74S	1.000
19:1207140:C:A	A76D	1.000
19:1207143:T:A	V77D	1.000
19:1207145:A:C	K78Q	1.000
19:1207145:A:G	K78E	1.000
19:1207147:G:C	K78N	1.000
19:1207147:G:T	K78N	1.000
19:1207149:T:A	I79N	1.000

dbSNP variants (sampled 300 via entrez): RS1000190042 (19:1213744 G>A), RS1000210972 (19:1222536 C>A,T), RS1000261203 (19:1218272 C>T), RS1000284683 (19:1213585 C>T), RS1000508153 (19:1207906 C>T), RS1000619039 (19:1212685 T>C), RS1000726326 (19:1212011 G>A), RS1000755581 (19:1216785 T>G), RS1000798577 (19:1211831 A>T), RS1000831724 (19:1227080 G>A), RS1000885403 (19:1224210 G>A,T), RS1000953655 (19:1224682 C>T), RS1000988286 (19:1226910 G>A), RS1001000431 (19:1217292 C>T), RS1001026620 (19:1207766 C>T)

Disease associations

OMIM: gene MIM:602216 | disease phenotypes: MIM:175200, MIM:155600, MIM:273300, MIM:260350, MIM:167000, MIM:175100, MIM:613659, MIM:268210, MIM:131100, MIM:612555, MIM:617146

GenCC curated gene-disease

Disease	Classification	Inheritance
Peutz-Jeghers syndrome	Definitive	Autosomal dominant
familial pancreatic carcinoma	Definitive	Autosomal dominant
familial ovarian cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Peutz-Jeghers syndrome	Definitive	AD
familial ovarian cancer	No Known Disease Relationship	AD

Mondo (29): Peutz-Jeghers syndrome (MONDO:0008280), melanoma, cutaneous malignant, susceptibility to, 1 (MONDO:0007963), hereditary neoplastic syndrome (MONDO:0015356), generalized juvenile polyposis/juvenile polyposis coli (MONDO:0008276), colon carcinoma (MONDO:0002032), testicular germ cell tumor (MONDO:0010108), hereditary breast ovarian cancer syndrome (MONDO:0003582), breast cancer (MONDO:0007254), breast carcinoma (MONDO:0004989), exocrine pancreatic carcinoma (MONDO:0005192), familial pancreatic carcinoma (MONDO:0015278), familial ovarian cancer (MONDO:0016248), testicular cancer (MONDO:0005447), ovarian cancer (MONDO:0008170), familial adenomatous polyposis 1 (MONDO:0021056)

Orphanet (14): Peutz-Jeghers syndrome (Orphanet:2869), Inherited cancer-predisposing syndrome (Orphanet:140162), Familial melanoma (Orphanet:618), Generalized juvenile polyposis/juvenile polyposis coli (Orphanet:329971), Germ cell tumor of testis (Orphanet:363504), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074), Rare ovarian cancer (Orphanet:213500), Hepatoblastoma (Orphanet:449), Embryonal rhabdomyosarcoma (Orphanet:99757), Multiple endocrine neoplasia type 1 (Orphanet:652), OBSOLETE: Familial ovarian cancer (Orphanet:213517), NON RARE IN EUROPE: Melanoma (Orphanet:411533)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000027	Azoospermia
HP:0000069	Abnormality of the ureter
HP:0000138	Ovarian cyst
HP:0000366	Abnormality of the nose
HP:0000478	Abnormality of the eye
HP:0000771	Gynecomastia
HP:0001003	Multiple lentigines
HP:0001034	Hypermelanotic macule
HP:0001054	Numerous nevi
HP:0001062	Atypical nevus
HP:0001074	Atypical nevi in non-sun exposed areas
HP:0001080	Biliary tract abnormality
HP:0001217	Clubbing
HP:0001442	Typified by somatic mosaicism
HP:0001891	Iron deficiency anemia
HP:0001903	Anemia
HP:0002013	Vomiting
HP:0002027	Abdominal pain
HP:0002035	Rectal prolapse
HP:0002086	Abnormality of the respiratory system
HP:0002239	Gastrointestinal hemorrhage
HP:0002576	Intussusception
HP:0002584	Intestinal bleeding
HP:0002664	Neoplasm
HP:0002672	Gastrointestinal carcinoma
HP:0002894	Neoplasm of the pancreas
HP:0002898	Embryonal neoplasm
HP:0003002	Breast carcinoma
HP:0003581	Adult onset

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001282_4	Psychosis in Alzheimer’s disease	8.000000e-06
GCST004131_43	Inflammatory bowel disease	5.000000e-17
GCST004132_20	Crohn’s disease	1.000000e-20
GCST004627_181	Lymphocyte count	6.000000e-10
GCST005537_44	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-09
GCST007995_8	Asthma (childhood onset)	2.000000e-08
GCST010320_10	PR interval	3.000000e-11
GCST010321_64	PR interval	7.000000e-11
GCST012202_5	Distal/Left-sided colorectal cancer	2.000000e-08
GCST90002388_29	Lymphocyte count	8.000000e-22
GCST90002389_257	Lymphocyte percentage of white cells	4.000000e-21
GCST90002399_213	Neutrophil percentage of white cells	1.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005940	psychotic symptoms
EFO:0004587	lymphocyte count
EFO:0004462	PR interval
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001932	Brain Neoplasms	C04.588.614.250.195; C10.228.140.211; C10.551.240.250
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D018197	Hepatoblastoma	C04.557.435.380
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008545	Melanoma	C04.557.465.625.650.510; C04.557.580.625.650.510; C04.557.665.510; C04.588.805.377; C17.800.882.445
D018761	Multiple Endocrine Neoplasia Type 1	C04.588.322.400.500; C04.651.600.500; C04.700.630.500; C16.320.700.630.500; C19.344.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D010580	Peutz-Jeghers Syndrome	C04.700.633; C06.405.469.578.750; C16.320.700.667; C17.800.621.430.530.550.625
D013736	Testicular Neoplasms	C04.588.322.762; C04.588.945.440.915; C12.100.500.260.937; C12.200.294.260.937; C12.200.758.409.937; C12.900.619.937; C19.344.762; C19.391.829.782
C535837	Pancreatic carcinoma, familial (supp.)
C563236	Testicular Germ Cell Tumor (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885534 (PROTEIN COMPLEX), CHEMBL5606 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 116,890 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1231124	AZD-1480	2	1,576
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622
CHEMBL3128043	PF-03758309	1	233
CHEMBL3545085	XL-228	1	936

Clinical evidence (CIViC)

Drug × variant × indication: 11 predictive associations from 12 curated evidence items; also 2 predisposing, 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
STK11 Mutation	Vistusertib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID12514
STK11 Mutation	Chemoradiotherapy	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID12911
STK11 Mutation	Cisplatin/Pembrolizumab/Pemetrexed Regimen	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID12338
STK11 Mutation	Radiation Therapy	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID12912
STK11 Mutation	Nivolumab + Atezolizumab + Pembrolizumab	Lung Adenocarcinoma	Resistance	CIViC B	EID6441
STK11 D194E	Everolimus	Pancreatic Cancer	Sensitivity/Response	CIViC C	EID1617
STK11 Loss	Sirolimus	Peutz-Jeghers Syndrome	Sensitivity/Response	CIViC D	EID1618 +1
STK11 Loss	Roflumilast	Pancreatic Ductal Adenocarcinoma	Sensitivity/Response	CIViC D	EID12555
STK11 Loss	Everolimus + Sirolimus	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID1620
STK11 Underexpression	SB202190	Prostate Cancer	Sensitivity/Response	CIViC D	EID751
STK11 Loss	Selumetinib + Docetaxel	Lung Non-small Cell Carcinoma	Resistance	CIViC D	EID1144

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — LKB subfamily

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

38 potent at pChembl≥5 of 38 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	PACRITINIB
7.82	Kd	15.19	nM	CHEMBL5653589
7.75	Kd	18	nM	NINTEDANIB
7.74	ED50	18.01	nM	CHEMBL5653589
7.42	Kd	38	nM	SUNITINIB
7.31	IC50	48.7	nM	STAUROSPORINE
7.24	Kd	57	nM	LESTAURTINIB
7.21	Kd	61	nM	STAUROSPORINE
7.16	IC50	68.5	nM	STAUROSPORINE
7.15	IC50	70.9	nM	STAUROSPORINE
6.62	Kd	240	nM	KW-2449
6.51	Kd	310	nM	FEDRATINIB
6.46	Kd	350	nM	MIDOSTAURIN
6.44	Kd	360	nM	SU-014813
6.42	Kd	380	nM	CHEMBL516312
6.36	Kd	434	nM	PF-03758309
6.30	Kd	497	nM	DINACICLIB
6.20	Kd	626	nM	PF-00562271
6.15	Kd	714	nM	AZD-1480
5.89	Kd	1300	nM	TOZASERTIB
5.70	Kd	2013	nM	CHEMBL3752910
5.62	ED50	2386	nM	CHEMBL3752910
5.58	Kd	2600	nM	PHA-665752
5.51	Kd	3077	nM	XL-228
5.47	Kd	3400	nM	R-406
5.43	Kd	3700	nM	DOVITINIB
5.36	Kd	4375	nM	CHEMBL3990456
5.23	Kd	5900	nM	RUBOXISTAURIN

PubChem BioAssay actives

36 with measured affinity, of 963 total; 23 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Pacritinib	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149508: Binding affinity to human STK11 incubated for 45 mins by Kinobead based pull down assay	kd	0.0152	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624798: Binding constant for LKB1 kinase domain	kd	0.0180	uM
Sunitinib	435909: Binding constant for full-length LKB1	kd	0.0380	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715295: Inhibition of human LKB1 using LSNLYHQGKFLQTFCGSPLYRRR as substrate by [gamma-33P]-ATP assay	ic50	0.0487	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507590: Binding affinity to LKB1	kd	0.0570	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624798: Binding constant for LKB1 kinase domain	kd	0.2400	uM
Fedratinib	624798: Binding constant for LKB1 kinase domain	kd	0.3100	uM
Midostaurin	435909: Binding constant for full-length LKB1	kd	0.3500	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435909: Binding constant for full-length LKB1	kd	0.3600	uM
N-[5-(4-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide	389033: Binding affinity to human LKB1	kd	0.3800	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4340	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4970	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.6260	uM
5-chloro-2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.7140	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435909: Binding constant for full-length LKB1	kd	1.3000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149508: Binding affinity to human STK11 incubated for 45 mins by Kinobead based pull down assay	kd	2.0130	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624798: Binding constant for LKB1 kinase domain	kd	2.6000	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.0770	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624798: Binding constant for LKB1 kinase domain	kd	3.4000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435909: Binding constant for full-length LKB1	kd	3.7000	uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide	1425178: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	4.3750	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	624798: Binding constant for LKB1 kinase domain	kd	5.9000	uM

CTD chemical–gene interactions

73 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases phosphorylation, affects binding, increases reaction, decreases acetylation, increases expression (+6 more)	6
STO 609	affects response to substance, decreases reaction, increases phosphorylation	2
dorsomorphin	decreases phosphorylation, decreases reaction, increases phosphorylation	2
(+)-JQ1 compound	increases expression, increases response to substance, increases activity, increases cleavage, decreases expression (+1 more)	2
Cisplatin	affects binding, increases reaction, increases degradation, increases phosphorylation, decreases reaction (+2 more)	2
Metformin	decreases phosphorylation, decreases reaction, affects reaction, increases phosphorylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
geldanamycin	decreases expression, decreases phosphorylation, decreases reaction	1
thymoquinone	decreases phosphorylation, decreases reaction	1
triphenyl phosphate	affects expression	1
5-methyltetrahydrofolate	decreases phosphorylation, decreases reaction	1
bisphenol A	increases methylation, affects cotreatment	1
beta-ionone	increases phosphorylation, affects reaction, decreases expression, increases cleavage, increases lipidation	1
deoxypodophyllotoxin	increases phosphorylation	1
lonidamine	increases phosphorylation	1
bromopyruvate	decreases expression	1
sodium arsenite	decreases expression	1
3-aminobenzamide	decreases reaction, increases phosphorylation	1
ginsenoside Rg2	decreases reaction, increases phosphorylation	1
AICA ribonucleotide	decreases phosphorylation, decreases reaction	1
2-chloroethyl ethyl sulfide	decreases stability, increases degradation, increases expression, decreases reaction, decreases expression (+1 more)	1
puag-haad	increases phosphorylation	1
bafilomycin A1	decreases expression, decreases reaction	1
gastrodin	increases phosphorylation	1
rubimaillin	increases phosphorylation	1
N-methylisoindigotin	decreases phosphorylation	1
ginsenoside Re	increases phosphorylation	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases phosphorylation, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

244 unique, capped per target: 244 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2014944	Binding	Inhibition of LKB1-MO25a-STRADa at 10 uM	Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2,031 cell lines: 2,027 cancer cell line, 2 transformed cell line, 1 hybrid cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0013	MOLT-4	Cancer cell line	Male
CVCL_0023	A-549	Cancer cell line	Male
CVCL_0105	DU145	Cancer cell line	Male
CVCL_0459	NCI-H460	Cancer cell line	Male
CVCL_0C87	MOCHA	Cancer cell line	Male
CVCL_1150	CTV-1	Cancer cell line	Male
CVCL_1475	NCI-H1563	Cancer cell line	Male
CVCL_1547	NCI-H23	Cancer cell line	Male
CVCL_1968	BM-1604	Cancer cell line	Male
CVCL_1D09	HROBML03	Cancer cell line	Male

Clinical trials (associated diseases)

312 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03781050	PHASE4	UNKNOWN	Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
NCT06001476	PHASE4	UNKNOWN	Cold Snare Polypectomy for Small Bowel Polyps in Patients With Peutz-Jeghers Syndrome
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT00002968	PHASE3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	PHASE3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	PHASE3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	PHASE3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	PHASE3	COMPLETED	Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer
NCT00188305	PHASE3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	PHASE3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	PHASE3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	PHASE3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	PHASE3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	PHASE3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	PHASE3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	PHASE3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	PHASE3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	PHASE3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	PHASE3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	PHASE3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy