STK11
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
STK11 (HGNC:11389) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
serine/threonine kinase 11
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
PJS, LKB1
%HI
15.32(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.36(Read more about gnomAD LOEUF score)
Cytoband
19p13.3
Genomic Coordinates
GRCh37/hg19: chr19:1205777-1228430 NCBI Ensembl UCSC
GRCh38/hg38: chr19:1205778-1228431 NCBI Ensembl UCSC
MANE Select Transcript
NM_000455.5 ENST00000326873.12 (Read more about MANE Select)
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 fam... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-4436
ClinGen Curation ID:
CCID:007948
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
11/10/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 2563227
    Hearle et al 2006 report multiple (38) unrelated probands with Peutz-Jeghers syndrome assessed for STK11 mutations (exon deletions, nonsense, missense and loss of function from in-frame deletions in kinase domain). 16% (6/38) carry exon deletions and total 50% (19/38) had mutations in STK11: "four nonsense mutations, six deletions, and two insertions predicted to lead to truncation of the expressed protein, four missense mutations, and three splice site mutations".
  • PUBMED: 20623358
    Resta et al 2010 reports multiple unrelated probands with Peutz-Jeghers syndrome carrying large deletions detected by MLPA (15/51 ~29%)
  • PUBMED: 23892522
    Zheng, et al. (2013) presented 5 unrelated Chinese Peutz-Jeghers syndrome (PJS) cases (age of onset between 1 and 5 years; Table 2) as well as their healthy parents, and screened 50 controls for missense variants. Direct sequencing of STK11 revealed 5 de novo variants (three frameshift (c.519insTGTG (p.His174Cysfs*92), c.792_793insT (p.Glu265*), and c.334_335insC (p.Gln112Profs*50)), one missense, and one in-frame deletion; Table 2) in 5 cases, respectively. The 3 frameshift variants were present in a heterozygous state and were absent from gnomAD as of November 2021.
  • PUBMED: 28231849
    Chen, et al. (2017) presented a Chinese Peutz-Jeghers (PJ) syndrome family with 5 affected individuals across 3 generations, and 200 controls of the same ethnicity (not younger than 40 years of age). Sanger sequencing of STK11 showed presence of heterozygous c.440_441delGT (p.Arg147Leufs*15) variant in 4 individuals: in 4 years old male proband (age at first diagnosis of PJ polyps of 1 year); his 13 years old brother (age at first diagnosis of PJ polyps of 2 years); his 46 years old father (age at first diagnosis of PJ polyps of 15 years); and his 38 years old uncle (age at first diagnosis of PJ polyps of 16 years). This variant was absent from the control group as well as from gnomAD as of November 2021.
HI Evidence Comments:
PMID: 12060709 Jishage, et al. (2002): presented an in vivo functional study by analyzing mice with heterozygous (Stk11-/+) or homozygous (Stk11-/-) knock-out of STK11 (also reported as LKB1) gene. The result showed that Stk11-/+ mice developed multiple gastric polyps, while Stk11-/- mice experienced in utero lethality. Deletions (whole gene and exonic) and loss-of-function mutations in STK11 are associated with Peutz-Jeghers syndrome (PJS). From OMIM: "<PJS is> an autosomal dominant disorder characterized by melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyps; and an increased risk of various neoplasms."

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time (11/3/2021) there is no evidence for triplosensitivity of this gene.

Genomic View

Select assembly: (NC_000019.9) (NC_000019.10)