Peutz-Jeghers syndrome

Summary

Peutz-Jeghers syndrome (MONDO:0008280) is a disease caused by STK11 (GenCC Definitive), with 4 cohort genes and 16 clinical trials. Molecularly, STK11 Loss confers sensitivity to Sirolimus in Peutz-Jeghers Syndrome (CIViC Level D). Top therapeutic interventions include secretin and sirolimus.

At a glance

• Prevalence: 1-9 / 1 000 000 (Uruguay) [Orphanet-validated]
• Causal gene: STK11 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 2,363
• Phenotypes (HPO): 33
• Clinical trials: 16
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.65	Uruguay	Validated
Prevalence at birth	1-9 / 100 000	2.2	Worldwide	Not yet validated
Point prevalence	1-9 / 1 000 000	0.4	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0001003	Multiple lentigines	Very frequent (80-99%)
HP:0002672	Gastrointestinal carcinoma	Very frequent (80-99%)
HP:0011024	Abnormality of the gastrointestinal tract	Very frequent (80-99%)
HP:0012733	Macule	Very frequent (80-99%)
HP:0100669	Abnormal pigmentation of the oral mucosa	Very frequent (80-99%)
HP:0002239	Gastrointestinal hemorrhage	Frequent (30-79%)
HP:0000069	Abnormality of the ureter	Occasional (5-29%)
HP:0000366	Abnormality of the nose	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002035	Rectal prolapse	Occasional (5-29%)
HP:0002086	Abnormality of the respiratory system	Occasional (5-29%)
HP:0002664	Neoplasm	Occasional (5-29%)
HP:0003002	Breast carcinoma	Occasional (5-29%)
HP:0005214	Intestinal obstruction	Occasional (5-29%)
HP:0005244	Gastrointestinal infarctions	Occasional (5-29%)
HP:0005264	Abnormality of the gallbladder	Occasional (5-29%)
HP:0005562	Multiple renal cysts	Occasional (5-29%)
HP:0005584	Renal cell carcinoma	Occasional (5-29%)
HP:0006725	Pancreatic adenocarcinoma	Occasional (5-29%)
HP:0008675	Enlarged polycystic ovaries	Occasional (5-29%)
HP:0012126	Stomach cancer	Occasional (5-29%)
HP:0012720	Neoplasm of the nose	Occasional (5-29%)
HP:0030079	Cervix cancer	Occasional (5-29%)
HP:0100273	Neoplasm of the colon	Occasional (5-29%)
HP:0100526	Neoplasm of the lung	Occasional (5-29%)
HP:0100574	Biliary tract neoplasm	Occasional (5-29%)
HP:0100582	Nasal polyposis	Occasional (5-29%)
HP:0100644	Melanonychia	Occasional (5-29%)
HP:0100743	Neoplasm of the rectum	Occasional (5-29%)
HP:0100751	Esophageal neoplasm	Occasional (5-29%)
HP:0100833	Neoplasm of the small intestine	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Peutz-Jeghers syndrome
Mondo ID	MONDO:0008280
MeSH	D010580
OMIM	175200
Orphanet	2869
DOID	DOID:3852
ICD-11	969253189
NCIT	C3324
SNOMED CT	54411001
UMLS	C0031269
MedGen	18404
GARD	0007378
MedDRA	10034764
NORD	1570
Is cancer (heuristic)	no

Also known as: hamartomatous intestinal polyposis · Jeghers-Peutz syndrome · lentiginosis, perioral · periorificial lentiginosis syndrome · Peutz Jeghers polyposis · Peutz Jeghers Syndrome · Peutz’s syndrome · Peutz-Jeghers syndrome · PJS · polyps and spots syndrome · STK11-related Peutz-Jeghers syndrome

Data availability: 2,363 ClinVar variants · 5 GenCC gene-disease records · 15 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Peutz-Jeghers syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

181 uncertain significance, 131 conflicting classifications of pathogenicity, 117 benign/likely benign, 101 likely benign, 50 pathogenic, 9 likely pathogenic, 8 pathogenic/likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703549	GRCh37/hg19 19p13.3(chr19:260911-1319319)	ABCA7	Pathogenic	no assertion criteria provided
1077101	NM_000455.5(STK11):c.1010_1011del (p.Val337fs)	LOC130062899	Pathogenic	criteria provided, multiple submitters, no conflicts
1801558	NM_000455.5(STK11):c.1090C>T (p.Gln364Ter)	LOC130062899	Pathogenic	criteria provided, multiple submitters, no conflicts
1065904	NM_000455.5(STK11):c.863-1G>C	STK11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068630	NM_000455.5(STK11):c.734+1G>A	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1069286	NM_000455.5(STK11):c.889_890del (p.Arg297fs)	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1071855	NC_000019.9:g.(?1218406)(1218509_?)del	STK11	Pathogenic	criteria provided, single submitter
1072061	NM_000455.5(STK11):c.788T>A (p.Leu263Ter)	STK11	Pathogenic	criteria provided, single submitter
1072081	NC_000019.9:g.(?1221107)(1227749_?)del	STK11	Pathogenic	criteria provided, single submitter
1073428	NM_000455.5(STK11):c.354_362del (p.Tyr118_Glu121delinsTer)	STK11	Pathogenic	criteria provided, single submitter
1073558	NM_000455.5(STK11):c.640_653del (p.Gln214fs)	STK11	Pathogenic	criteria provided, single submitter
1073837	NC_000019.9:g.(?1206913)(1207212_?)del	STK11	Pathogenic	criteria provided, single submitter
1073838	NC_000019.9:g.(?1206903)(1207212_?)del	STK11	Pathogenic	criteria provided, single submitter
1073839	NC_000019.9:g.(?1220366)(1220510_?)del	STK11	Pathogenic	criteria provided, single submitter
1073840	NC_000019.9:g.(?1218406)(1219422_?)del	STK11	Pathogenic	criteria provided, single submitter
1073934	NM_000455.5(STK11):c.332_333insG (p.Ile111fs)	STK11	Pathogenic	criteria provided, single submitter
1075652	NM_000455.5(STK11):c.291-1G>C	STK11	Pathogenic	criteria provided, single submitter
1075653	NM_000455.5(STK11):c.334C>T (p.Gln112Ter)	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1075654	NM_000455.5(STK11):c.464+1dup	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1075763	NM_000455.5(STK11):c.608_627del (p.Pro203fs)	STK11	Pathogenic	criteria provided, single submitter
1075905	NC_000019.9:g.(?1206907)(1226652_?)del	STK11	Pathogenic	criteria provided, single submitter
1076021	NM_000455.5(STK11):c.145dup (p.Tyr49fs)	STK11	Pathogenic	criteria provided, single submitter
1342166	NM_000455.5(STK11):c.735-6A>G	STK11	Pathogenic	criteria provided, single submitter
1350425	NC_000019.9:g.(?1206913)(1219422_?)del	STK11	Pathogenic	criteria provided, single submitter
1359304	NM_000455.5(STK11):c.841_842dup (p.Leu282fs)	STK11	Pathogenic	criteria provided, single submitter
1359873	NM_000455.5(STK11):c.464+1G>T	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1360522	NM_000455.5(STK11):c.597+2T>A	STK11	Pathogenic	criteria provided, single submitter
1370402	NM_000455.5(STK11):c.141dup (p.Lys48fs)	STK11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1370818	NM_000455.5(STK11):c.290+1G>C	STK11	Pathogenic	criteria provided, multiple submitters, no conflicts
1370938	NM_000455.5(STK11):c.916C>T (p.His306Tyr)	STK11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
STK11	Definitive	Autosomal dominant	Peutz-Jeghers syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STK11	Orphanet:2869	Peutz-Jeghers syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	gencc,clinvar,civic_evidence
CBARP	HGNC:28617	ENSG00000099625	Q8N350	Voltage-dependent calcium channel beta subunit-associated regulatory protein	clinvar
ARID3A	HGNC:3031	ENSG00000116017	Q99856	AT-rich interactive domain-containing protein 3A	clinvar
ABCA7	HGNC:37	ENSG00000064687	Q8IZY2	Phospholipid-transporting ATPase ABCA7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STK11	Serine/threonine-protein kinase STK11	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…
CBARP	Voltage-dependent calcium channel beta subunit-associated regulatory protein	Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits.
ARID3A	AT-rich interactive domain-containing protein 3A	Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation.
ABCA7	Phospholipid-transporting ATPase ABCA7	Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	19.4×	0.151
Kinase	1	6.9×	0.205
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CBARP	Other/Unknown	no		CBARP
ARID3A	Other/Unknown	no		ARID_dom, REKLES_domain, ARID_dom_sf
ABCA7	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	2
pituitary gland	2
hindlimb stylopod muscle	1
left testis	1
right testis	1
nucleus accumbens	1
blood	1
monocyte	1
mononuclear cell	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
CBARP	182	ubiquitous	yes	adenohypophysis, nucleus accumbens, pituitary gland
ARID3A	187	ubiquitous	marker	monocyte, mononuclear cell, blood
ABCA7	231	ubiquitous	marker	granulocyte, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STK11	5,146
ARID3A	2,145
ABCA7	1,520
CBARP	523

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA7	Q8IZY2	6
STK11	Q15831	4
ARID3A	Q99856	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CBARP	Q8N350	52.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional Regulation by TP53	2	41.4×	0.015	STK11, ARID3A
AMPK inhibits chREBP transcriptional activation activity	1	475.8×	0.016	STK11
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	237.9×	0.016	ARID3A
FOXO-mediated transcription of cell death genes	1	237.9×	0.016	STK11
ABC transporters in lipid homeostasis	1	200.3×	0.016	ABCA7
TP53 Regulates Transcription of Cell Cycle Genes	1	181.3×	0.016	ARID3A
RNA Polymerase II Transcription	2	15.0×	0.016	STK11, ARID3A
Energy dependent regulation of mTOR by LKB1-AMPK	1	131.3×	0.017	STK11
FOXO-mediated transcription	1	112.0×	0.017	STK11
Gene expression (Transcription)	2	11.9×	0.017	STK11, ARID3A
MTOR signalling	1	88.5×	0.019	STK11
Generic Transcription Pathway	2	10.1×	0.020	STK11, ARID3A
Integration of energy metabolism	1	58.6×	0.025	STK11
Regulation of TP53 Activity	1	44.3×	0.030	STK11
ABC-family protein mediated transport	1	40.5×	0.030	ABCA7
Regulation of TP53 Activity through Phosphorylation	1	39.2×	0.030	STK11
Transport of small molecules	1	8.4×	0.128	ABCA7
Metabolism	1	3.9×	0.250	STK11
Signal Transduction	1	3.4×	0.267	STK11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to nucleus	2	175.5×	0.003	STK11, ABCA7
positive regulation of vesicle transport along microtubule	1	4213.0×	0.009	STK11
positive regulation of engulfment of apoptotic cell	1	2106.5×	0.009	ABCA7
negative regulation of calcium ion transmembrane transport	1	2106.5×	0.009	CBARP
apolipoprotein A-I-mediated signaling pathway	1	1053.2×	0.009	ABCA7
positive regulation of phospholipid efflux	1	1053.2×	0.009	ABCA7
negative regulation of voltage-gated calcium channel activity	1	842.6×	0.009	CBARP
regulation of amyloid precursor protein catabolic process	1	842.6×	0.009	ABCA7
plasma membrane raft organization	1	702.2×	0.009	ABCA7
negative regulation of epithelial cell proliferation involved in prostate gland development	1	702.2×	0.009	STK11
negative regulation of amyloid precursor protein biosynthetic process	1	526.6×	0.009	ABCA7
Golgi localization	1	526.6×	0.009	STK11
epithelial cell proliferation involved in prostate gland development	1	526.6×	0.009	STK11
amyloid-beta clearance by cellular catabolic process	1	526.6×	0.009	ABCA7
positive regulation of amyloid-beta clearance	1	526.6×	0.009	ABCA7
amyloid-beta formation	1	468.1×	0.009	ABCA7
negative regulation of calcium ion-dependent exocytosis	1	468.1×	0.009	CBARP
high-density lipoprotein particle assembly	1	421.3×	0.009	ABCA7
dendrite extension	1	421.3×	0.009	STK11
activation of protein kinase activity	1	383.0×	0.009	STK11
positive thymic T cell selection	1	351.1×	0.009	STK11
G1 to G0 transition	1	351.1×	0.009	STK11
cellular response to UV-B	1	351.1×	0.009	STK11
negative regulation of PERK-mediated unfolded protein response	1	351.1×	0.009	ABCA7
anoikis	1	324.1×	0.009	STK11
vasculature development	1	280.9×	0.009	STK11
phospholipid efflux	1	280.9×	0.009	ABCA7
negative regulation of endocytosis	1	234.1×	0.010	ABCA7
peptidyl-threonine phosphorylation	1	221.7×	0.010	STK11
regulation of Wnt signaling pathway	1	221.7×	0.010	STK11

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Everolimus.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 3

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
STK11	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STK11	17	4
CBARP	0	0
ARID3A	0	0
ABCA7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
DINACICLIB	3	STK11
DOVITINIB	3	STK11
LESTAURTINIB	3	STK11
RUBOXISTAURIN	3	STK11
AZD-1480	2	STK11
SU-014813	2	STK11
R-406	2	STK11
TOZASERTIB	2	STK11
PF-00562271	1	STK11
KW-2449	1	STK11
PF-03758309	1	STK11
XL-228	1	STK11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
STK11	244	Binding:244

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK11	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
STK11	244

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

17 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
DINACICLIB	3	STK11
DOVITINIB	3	STK11
LESTAURTINIB	3	STK11
RUBOXISTAURIN	3	STK11
AZD-1480	2	STK11
SU-014813	2	STK11
R-406	2	STK11
TOZASERTIB	2	STK11
PF-00562271	1	STK11
KW-2449	1	STK11
PF-03758309	1	STK11
XL-228	1	STK11

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	STK11
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ABCA7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CBARP, ARID3A

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CBARP	0	—
ARID3A	0	—
ABCA7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE4	2
PHASE2	2
PHASE3	1

Top trials by phase / activity

NCT	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
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT00811590	PHASE2	TERMINATED	Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome
NCT01178151	PHASE2	WITHDRAWN	Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT05692596	Not specified	ACTIVE_NOT_RECRUITING	The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
NCT06722534	Not specified	RECRUITING	Celecoxib for Prevention of Progression in Peutz-Jeghers Syndrome
NCT00001452	Not specified	COMPLETED	Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex
NCT00438906	Not specified	COMPLETED	Cancer of the Pancreas Screening Study (CAPS 3)
NCT00633607	Not specified	COMPLETED	Hereditary Colorectal and Associated Tumor Registry Study
NCT03806075	Not specified	UNKNOWN	Study of Accurate Diagnosis and Treatment of Peutz-Jeghers Syndrome
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06242457	Not specified	COMPLETED	Poorly Differentiated Adenocarcinoma of the Jejunum in a Patient With Peutz-Jeghers Syndrome: A Case Report

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SECRETIN	4	1
SIROLIMUS	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 2 curated evidence items; also 2 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
STK11 Loss	Sirolimus	Sensitivity/Response	CIViC D	EID1618 +1