STK11

Chr 19AD

serine/threonine kinase 11

Also known as: LKB1, PJS, hLKB1

NCBI Gene: 6794 ENSG00000118046 UniProt: Q15831

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. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

Melanoma, malignant, somaticMIM #155600

Pancreatic cancer, somaticMIM #260350

Peutz-Jeghers syndromeMIM #175200

Testicular tumor, somaticMIM #273300

UniProtTesticular germ cell tumor

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

1.6

Missense Z

0.24

LOEUF· LoF intolerant

Clinical Summary— STK11

🧬

Gene-Disease Validity (ClinGen)

Peutz-Jeghers syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.24LOEUF

pLI 0.993

Z-score 3.87

OE 0.05 (0.02–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.60Z-score

OE missense 0.73 (0.65–0.82)

203 obs / 277.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.24)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.33

0≤1.21.6

LoF obs/exp: 1 / 19.4Missense obs/exp: 203 / 277.9Syn Z: -2.90

0.4388th %ile

GOF

0.5465th %ile

LOF

0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.24

Literature Evidence

LOFHaploinsufficiency of STK11 and neighboring genes cause a contiguous gene syndrome including Peutz-Jeghers phenotype.PMID:22987620

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

STK11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

STK11-related Peutz-Jeghers syndrome

definitive

ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure

Cancer

G2P ↗

STK11-related pancreatic cancer

definitive

ADLoss Of FunctionAbsent Gene Product

Skin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING

NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21

NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Pancreas CancerExosomesExtracellular Vesicles

ExoLuminate Study for Early Detection of Pancreatic Cancer

RECRUITING

NCT05625529Biological DynamicsStarted 2022-12-19

Non Small Cell Lung Cancer Metastatic

First-line Therapy With Nivolumab Plus Ipilimumab in Combination With Chemotherapy for Metatastatic NSCLC (NICReWo Trial)

RECRUITING

NCT07190677Fondazione IRCCS Policlinico San Matteo di PaviaStarted 2025-01-17

CarcinomaNon-Small-Cell Lung CancerAdenocarcinoma

Synergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study

RECRUITING

NCT04401059Phase PHASE4Tian XieStarted 2020-11-09

Elemene plus first or third generation EGFR-TKIsFirst or third generation EGFR-TKIs

Non-small-cell Lung Cancer Patients

Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab

RECRUITING

NCT05568212Phase PHASE2Fondazione Ricerca TraslazionaleStarted 2022-05-02

DurvalumabOlaparib tabletSingle-agent chemotherapy

Lung Cancer

Feasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer

ACTIVE NOT RECRUITING

NCT06301295Phase NAPusan National University HospitalStarted 2024-05-29

Ultarthin bronchoscopy with intratumoral washing

Advanced Malignant Solid NeoplasmMetastatic Malignant Solid NeoplasmNF1 Mutation Positive Malignant Peripheral Nerve Sheath Tumor

Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study

ACTIVE NOT RECRUITING

NCT03872427Phase PHASE2National Cancer Institute (NCI)Started 2019-12-14

Biospecimen CollectionComputed TomographyMagnetic Resonance Imaging

Hereditary Pancreatic Cancer

The PREPAIRD Study: Personalized Surveillance for Early Detection of Pancreatic Cancer in High Risk Individuals

ENROLLING BY INVITATION

NCT05740111Phase NAOslo University HospitalStarted 2022-09-01

Annual surveillance

Pancreas CancerPeutz-Jeghers Syndrome (PJS)Gene Mutation

The Cancer of the Pancreas Screening-5 CAPS5)Study

RECRUITING

NCT02000089Phase PHASE3Johns Hopkins UniversityStarted 2014-01-06