Gene Detail

Gene Symbol STK11
Synonyms hLKB1 | LKB1 | PJS
Gene Description STK11, serine/threonine kinase 11, is involved in cell metabolism, growth, polarity, and tumor suppression through the regulation of AMPK family members (PMID: 26398719). Germline STK11 mutations cause Peutz-Jeghers syndrome and somatic STK11 mutations have been identified in melanoma, lung, pancreatic, cervical, and endometrial cancers (PMID: 26877140, PMID: 29191602).
ACMG Incidental List v2.0:
Yes, Peutz-Jeghers syndrome (PMID: 27854360)
Entrez Id 6794
Chromosome 19
Map Location 19p13.3
Canonical Transcript NM_000455

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
E33* nonsense loss of function - predicted STK11 E33* results in a premature truncation of the Stk11 protein at amino acid 33 of 433 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), E33* is predicted to lead to a loss of Stk11 protein function.
K78E missense unknown STK11 K78E lies within the protein kinase domain of the Stk11 protein (UniProt.org). K78E has been identified in sequencing studies(PMID: 23630207, PMID: 2523465), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
Q137* nonsense loss of function - predicted STK11 Q137H* results in a premature truncation of the Stk11 protein at amino acid 137 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain, Q137* is predicted to lead to a loss of Stk11 protein function.
Y36D missense unknown STK11 Y36D does not lie within any known functional domains of the Stk11 protein (UniProt.org). Y36D has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Nov 2018).
H107L missense unknown STK11 H107L lies within the protein kinase domain of the Stk11 protein (UniProt.org). H107L has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
A241P missense unknown STK11 A241P lies within the protein kinase domain of the Stk11 protein (UniProt.org). A241P has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
S193F missense unknown STK11 S193F lies within the protein kinase domain of the Stk11 protein (UniProt.org). S193F has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
L282Afs*3 frameshift unknown STK11 L282Afs*3 indicates a shift in the reading frame starting at amino acid 282 and terminating 3 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). L282Afs*3 has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
N181Y missense unknown STK11 N181Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). N181Y has been identified in sequencing studies (PMID: 15121768), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
K48fs frameshift loss of function - predicted STK11 K48fs results in a change in the amino acid sequence of the Stk11 protein beginning at aa 48 of 433, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), K48fs is predicted to lead to a loss of Stk11 protein function.
P281L missense loss of function - predicted STK11 P281L lies within the protein kinase domain of the Stk11 protein (UniProt.org). P281L is predicted to confer a loss of function to the Stk11 protein, as indicated by a loss of kinase activity in an in vitro kinase assay (PMID: 10676634).
L183V missense unknown STK11 L183V lies within the protein kinase domain of the Stk11 protein (UniProt.org). L183V has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
Q100* nonsense loss of function - predicted STK11 Q100* results in a premature truncation of the Stk11 protein at amino acid 100 of 430 (UniProt.org). Due to the loss of the majority of the protein kinase domain, Q100* is predicted to confer a loss of Stk11 protein function.
A389T missense unknown STK11 A389T does not lie within any known functional domains of the Stk11 protein (UniProt.org). A389T has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
P179S missense unknown STK11 P179S lies within the protein kinase domain of the Stk11 protein (UniProt.org). P179S has been identified in sequencing studies (PMID: 22722839), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
W308C missense loss of function - predicted STK11 W308C lies within the protein kinase domain of the Stk11 protein (UniProt.org). W308C is predicted to confer a loss of function to the Stk11 protein, as demonstrated by loss of kinase activity (PMID: 9837816).
D350E missense unknown STK11 D350E does not lie within any known functional domains of the Stk11 protein (UniProt.org). D350E has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
E357K missense unknown STK11 E357K does not lie within any known functional domains of the Stk11 protein (UniProt.org). E357K has been identified in sequencing studies (PMID: 28642281), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
R333C missense unknown STK11 R333C does not lie within any known functional domains of the Stk11 protein (UniProt.org). R333C has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
D194H missense unknown STK11 D194H lies within the protein kinase domain of the Stk11 protein (UniProt.org). D194H has been identified in the scientific literature (PMID: 21816872), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
K44* nonsense loss of function - predicted STK11 K44* results in a premature truncation of the Stk11 protein at amino acid 44 of 433 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), K44* is predicted to lead to a loss of Stk11 protein function.
L195M missense unknown STK11 L195M lies within the protein kinase domain of the Stk11 protein (UniProt.org). L195M has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
E199* nonsense loss of function - predicted STK11 E199* results in a premature truncation of the Stk11 protein at amino acid 199 of 433 within the protein kinase domain (UniProt.org). Due to the loss of the majority of the protein kinase domain (UniProt.org), E199* is predicted to lead to a loss of Stk11 protein function.
D194Y missense loss of function - predicted STK11 D194Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). D194Y is predicted to confer a dominant negative loss of function to the Stk11 protein as demonstrated by the ability to suppress Ampk signaling (http://cancerres.aacrjournals.org/content/74/19_Supplement/4159.abstract).
E199Q missense no effect - predicted STK11 E199Q lies within the protein kinase domain of the Stk11 protein (UniProt.org). E199Q demonstrates kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943) and therefore, is predicted to have no effect on Stk11 protein function.
R297S missense unknown STK11 R297S lies within the protein kinase domain of the Stk11 protein (UniProt.org). R297S has been identified in sequencing studies (PMID: 21532627), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
E57Sfs*107 frameshift loss of function - predicted STK11 E57Sfs*107 indicates a shift in the reading frame starting at amino acid 57 and terminating 107 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, E57Sfs*107 is predicted to lead to a loss of Stk11 protein function.
Q159* nonsense loss of function - predicted STK11 Q159* results in a premature truncation of the Stk11 protein at amino acid 159 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain including the active site (UniProt.org), Q159* is predicted to lead to a loss of Stk11 protein function.
K41* nonsense loss of function - predicted STK11 K41* results in a premature truncation of the Stk11 protein at amino acid 41 of 433 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), K41* is predicted to lead to a loss of Stk11 protein function.
G196V missense unknown STK11 G196V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G196V has been identified in the scientific literature (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
S232P missense no effect STK11 S232P lies within the protein kinase domain of the Stk11 protein (UniProt.org). S232P demonstrates complex formation and kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943).
C278fs frameshift loss of function - predicted STK11 C278fs results in a change in the amino acid sequence of the Stk11 protein beginning at aa 278 of 433, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of part of the protein kinase domain (UniProt.org), C278fs is predicted to lead to a loss of Stk11 protein function.
P221L missense unknown STK11 P221L lies within the protein kinase domain of the Stk11 protein (UniProt.org). P221L has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
P179R missense unknown STK11 P179R lies within the protein kinase domain of the Stk11 protein (UniProt.org). P179R has been identified in sequencing studies (PMID: 28869103), but has not been characterized biochemically and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
P369S missense unknown STK11 P369S does not lie within any known functional domains of the Stk11 protein (UniProt.org). P369S has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
I111N missense unknown STK11 I111N lies within the protein kinase domain of the Stk11 protein (UniProt.org). I111N has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
D358N missense unknown STK11 D358N does not lie within any known functional domains of the Stk11 protein (UniProt.org). D358N has been identified in sequencing studies(PMID: 26319365), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
E57fs frameshift loss of function - predicted STK11 E57fs results in a change in the amino acid sequence of the Stk11 protein beginning at aa 57 of 433, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E57fs is predicted to lead to a loss of Stk11 protein function.
S19P missense unknown STK11 S19P does not lie within any known functional domains of the Stk11 protein (UniProt.org). S19P has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
N181I missense unknown STK11 N181I lies within the protein kinase domain of the Stk11 protein (UniProt.org). N181I has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Dec 2018).
E138* nonsense loss of function - predicted STK11 E138* results in a premature truncation of the Stk11 protein at amino acid 138 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain including the active site (UniProt.org), E138* is predicted to lead to a loss of Stk11 protein function.
Q123R missense no effect STK11 Q123R lies within the protein kinase domain of the Stk11 protein (UniProt.org). Q123R demonstrates complex formation and kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943).
R304W missense loss of function STK11 R304W lies within the protein kinase domain of the Stk11 protein (UniProt.org). R304W confers a loss of function to the Stk11 protein as demonstrated by loss of autophosphorylation and the inability to suppress growth in culture (PMID: 12552571).
I177N missense loss of function - predicted STK11 I177N lies within the protein kinase domain of the Stk11 protein (UniProt.org). I177N is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
loss unknown loss of function STK11 loss indicates loss of the STK11 gene, mRNA or protein.
Q170P missense loss of function - predicted STK11 Q170P lies within the protein kinase domain of the Stk11 protein (UniProt.org). Q170P is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
D176Y missense loss of function - predicted STK11 D176Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). D176Y is predicted to confer a loss of function to the Stk11 protein, as demonstrated by the inability to activate downstream kinase, Ampk (PMID: 19892943).
D355N missense unknown STK11 D355N does not lie within the any known functional domains of the Stk11 protein (UniProt.org). D355N has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
dec exp none no effect STK11 dec exp indicates decreased expression of the Stk11 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified
E121* nonsense loss of function - predicted STK11 E121* results in a premature truncation of the Stk11 protein at amino acid 121 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain, E121* is predicted to lead to a loss of Stk11 protein function.
D277Y missense loss of function - predicted STK11 D277Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). D277Y is predicted to confer a loss of function to the Stk11 protein, as demonstrated by reduced activation of the downstream kinase, Ampk (PMID: 19892943).
G242W missense unknown STK11 G242W lies within the protein kinase domain of the Stk11 protein (UniProt.org). G242W has been identified in the scientific literature (PMID: 11389158), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
I35Lfs*127 frameshift loss of function - predicted STK11 I35Lfs*127 indicates a shift in the reading frame starting at amino acid 35 and terminating 127 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, I35Lfs*127 is predicted to lead to a loss of Stk11 protein function.
G56V missense unknown STK11 G56V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G56V has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
D194E missense loss of function - predicted STK11 D194E lies within the protein kinase domain of the Stk11 protein (UniProt.org). D194E has not been biochemically characterized, but is associated with Peutz-Jehgers syndrome and is predicted to result in a loss of Stk11 protein function (PMID: 21189378).
W332* nonsense unknown STK11 W332* results in a premature truncation of the Stk11 protein at amino acid 332 of 433 (UniProt.org). W332* has been identified in sequencing studies (PMID: 17711506, PMID: 28978051), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
D53Tfs*11 frameshift loss of function - predicted STK11 D53Tfs*11 indicates a shift in the reading frame starting at amino acid 53 and terminating 11 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, D53Tfs*11 is predicted to lead to a loss of Stk11 protein function.
H168R missense unknown STK11 H168R lies within the protein kinase domain of the Stk11 protein (UniProt.org). H168R has been identified in sequencing studies (PMID: 25567908), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
P314H missense unknown STK11 P314H does not lie within any known functional domains of the Stk11 protein (UniProt.org). P314H has been identified in sequencing studies (PMID: 9809980), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
T250P missense loss of function - predicted STK11 T250P lies within the protein kinase domain of the Stk11 protein (UniProt.org). T250P is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
P179Q missense unknown STK11 P179Q lies within the protein kinase domain of the Stk11 protein (UniProt.org). P179Q has been identified in sequencing studies (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
D176A missense unknown STK11 D176A lies within the protein kinase domain of the Stk11 protein (UniProt.org). D176A has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
G56W missense unknown STK11 G56W lies within the protein kinase domain of the Stk11 protein (UniProt.org). G56W has been identified in sequencing studies (PMID: 25234657), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
V236A missense unknown STK11 V236A lies within the protein kinase domain of the Stk11 protein (UniProt.org). V236A has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
E317K missense unknown STK11 E317K does not lie within any known functional domains of the Stk11 protein (UniProt.org). E317K has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
D237N missense unknown STK11 D237N lies within the protein kinase domain of the Stk11 protein (UniProt.org). D237N has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
D194N missense unknown STK11 D194N lies within the protein kinase domain of the Stk11 protein (UniProt.org). D194N has not been biochemically characterized, but is predicted to result in a change of Stk11 binding energy based on computer modeling, thus, possibly resulting in a loss of enzyme function (PMID: 27081308).
M136R missense loss of function - predicted STK11 M136R lies within the protein kinase domain of the Stk11 protein (UniProt.org). M136R is predicted to confer a loss of function to the Stk11 protein, as demonstrated by loss of autophosphorylation (PMID: 14668798).
Q302* nonsense unknown STK11 Q302* results in a premature truncation of the Stk11 protein at amino acid 302 of 433 within the protein kinase domain (UniProt.org). Q302* has been identified in sequencing studies (PMID: 24652667, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Nov 2018).
K78N missense unknown STK11 K78N lies within the protein kinase domain of the Stk11 protein (UniProt.org). K78N has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
E199K missense loss of function - predicted STK11 E199K lies within the protein kinase domain of the Stk11 protein (UniProt.org). E199K is predicted to confer a loss of function to the Stk11 protein, as demonstrated by reduced activation of the downstream kinase Ampk in an in vitro assay (PMID: 19892943).
L67P missense loss of function - predicted STK11 L67P lies within the protein kinase domain of the Stk11 protein (UniProt.org). L67P is predicted to confer a loss of function to the Stk11 protein, as demonstrated by loss of kinase activity (PMID: 9837816).
Q37L missense unknown STK11 Q37L does not lie within any known functional domains of the Stk11 protein (UniProt.org). Q37L has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
T230P missense no effect STK11 T230P lies within the protein kinase domain of the Stk11 protein (UniProt.org). T230P demonstrates complex formation and kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943).
I248T missense unknown STK11 I248T lies within the protein kinase domain of the Stk11 protein (UniProt.org). I248T has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
R86G missense no effect STK11 R86G lies within the protein kinase domain of the Stk11 protein (UniProt.org). R86G demonstrates complex formation and kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943).
K78I missense loss of function STK11 K78I lies within the protein kinase domain of the Stk11 protein (UniProt.org). K78I confers a loss of function to the Stk11 protein, as demonstrated by loss of kinase activity in cell culture (PMID: 15731909, PMID: 9837816).
E223V missense loss of function - predicted STK11 E223V lies within the protein kinase domain of the Stk11 protein (UniProt.org). E223V is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase Ampk (PMID: 19892943).
G242V missense unknown STK11 G242V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G242V has been identified in the scientific literature (PMID: 11389158), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
G171S missense loss of function - predicted STK11 G171S lies within the protein kinase domain of the Stk11 protein (UniProt.org). G171S is predicted to confer a loss of function to the Stk11 protein, as demonstrated by reduced activation of the downstream kinase, Ampk (PMID: 19892943).
H174Y missense unknown STK11 H174Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). H174Y has been identified in sequencing studies (PMID: 24292813), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
F157S missense loss of function - predicted STK11 F157S lies within the protein kinase domain of the Stk11 protein (UniProt.org). F157S is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
D343N missense unknown STK11 D343N does not lie within any known functional domains of the Stk11 protein (UniProt.org). D343N has been identified in sequencing studies (PMID: 26354930), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
L245R missense loss of function - predicted STK11 L245R lies within the protein kinase domain of the Stk11 protein (UniProt.org). L245R is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
Q123* nonsense loss of function - predicted STK11 Q123* results in a premature truncation of the Stk11 protein at amino acid 123 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain, Q123* is predicted to lead to a loss of Stk11 protein function.
L285Q missense loss of function - predicted STK11 L285Q lies within the protein kinase domain of the Stk11 protein (UniProt.org). L285Q is predicted to confer a loss of function to the Stk11 protein, as demonstrated byits inability to activate the downstream kinase, Ampk (PMID: 19892943).
P294L missense unknown STK11 P294L lies within the protein kinase domain of the Stk11 protein (UniProt.org). P294L has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
V320fs frameshift unknown STK11 V320fs results in a change in the amino acid sequence of the Stk11 protein beginning at aa 320 of 433, likely resulting in premature truncation of the functional protein (UniProt.org). V320fs has been identified in sequencing studies (PMID: 28884744, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Nov 2018).
G163D missense loss of function - predicted STK11 G163D lies within the protein kinase domain of the Stk11 protein (UniProt.org). G163D is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
D176N missense loss of function - predicted STK11 D176N lies within the protein kinase domain of the Stk11 protein (UniProt.org). D176N is predicted to confer a loss of function to the Stk11 protein, as demonstrated by loss of kinase activity (PMID: 9837816).
I303S missense unknown STK11 I303S lies within the protein kinase domain of the Stk11 protein (UniProt.org). I303S has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
E165* nonsense loss of function - predicted STK11 E165* results in a premature truncation of the Stk11 protein at amino acid 165 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain including the active site (UniProt.org), E165* is predicted to lead to a loss of Stk11 protein function.
C132F missense unknown STK11 C132F lies within the protein kinase domain of the Stk11 protein (UniProt.org). C132F has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
I177T missense unknown STK11 I177T lies within the protein kinase domain of the Stk11 protein (UniProt.org). I177T has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
Y272H missense loss of function - predicted STK11 Y272H lies within the protein kinase domain of the Stk11 protein (UniProt.org). Y272H is predicted to confer a loss of function to the Stk11 protein, as demonstrated by reduced activation of the downstream kinase, Ampk (PMID: 19892943).
E70* nonsense loss of function - predicted STK11 E70* results in a premature truncation of the Stk11 protein at amino acid 70 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain, E70* is predicted to lead to a loss of Stk11 protein function.
inact mut unknown loss of function STK11 inact mut indicates that this variant results in a loss of function of the STK11 protein. However, the specific amino acid change has not been identified.
Y60* nonsense loss of function - predicted STK11 Y60* results in a premature truncation of the Stk11 protein at amino acid 60 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain including the active site (UniProt.org), Y60* is predicted to lead to a loss of Stk11 protein function.
Q170* nonsense loss of function - predicted STK11 Q170* results in a premature truncation of the Stk11 protein at amino acid 170 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain including the active site (UniProt.org), Q170* is predicted to lead to a loss of Stk11 protein function.
G61Afs*3 frameshift loss of function - predicted STK11 G61Afs*3 indicates a shift in the reading frame starting at amino acid 61 and terminating 3 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, G61Afs*3 is predicted to lead to a loss of Stk11 protein function.
mutant unknown unknown STK11 mutant indicates and unspecified mutation in the STK11 gene.
P281Rfs*6 frameshift unknown STK11 P281Rfs*6 indicates a shift in the reading frame starting at amino acid 281 and terminating 6 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). P281Rfs*6 has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
P281fs frameshift loss of function - predicted STK11 P281fs likely results in a premature truncation of the Stk11 protein at amino acid 281 of 433 (UniProt.org). STK11 P281fs is predicted to confer a loss of function to the Stk11 protein, as demonstrated by lack of kinase activity (http://cancerres.aacrjournals.org/content/74/19_Supplement/4159.abstract).
A205T missense loss of function STK11 A205T lies within the protein kinase domain of the Stk11 protein (UniProt.org). A205T results in decreased Stk11 kinase activity and loss of growth inhibition in cell culture (PMID: 16407837).
F354L missense loss of function STK11 F354L lies within the C-terminal region of the Stk11 protein (PMID: 15800014). F354L does not disrupt Stk11 autophosphorylation or growth suppression by Stk11, but results in decreased AMPK phosphorylation and increased mTOR signaling, and alters cell polarization in culture (PMID: 15800014).
R304G missense unknown STK11 R304G lies within the protein kinase domain of the Stk11 protein (UniProt.org). R304G has been identified in sequencing studies (PMID: 21532627), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
H174D missense unknown STK11 H174D lies within the protein kinase domain of the Stk11 protein (UniProt.org). H174D has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
S419F missense unknown STK11 S419F does not lie within any known functional domains of the Stk11 protein (UniProt.org). S419F has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
Q214* nonsense loss of function - predicted STK11 Q214* results in a premature truncation of the Stk11 protein at amino acid 214 of 433 within the protein kinase domain (UniProt.org). Due to the loss of part of the protein kinase domain (UniProt.org), Q214* is predicted to lead to a loss of Stk11 protein function.
R310P missense unknown STK11 R310P does not lie within any known functional domains of the Stk11 protein (UniProt.org). R310P has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
G251V missense unknown STK11 G251V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G251V has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
Q220* nonsense unknown STK11 Q220* results in a premature truncation of the Stk11 protein at amino acid 220 of 433 within the protein kinase domain (UniProt.org). Q220* has been identified in sequencing studies (PMID: 26087898), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
D359Y missense unknown STK11 D359Y does not lie within any known functional domains of the Stk11 protein (UniProt.org). D359Y has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
G251F missense unknown STK11 G251F lies within the protein kinase domain of the Stk11 protein (UniProt.org). G251F has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
K78A missense loss of function - predicted STK11 K78A lies within the protein kinase domain to the Stk11 protein (UniProt.org). K78A is predicted to confer a loss of function to the Stk11 protein, as demonstrated by lack of kinase activity (PMID: 15800014).
W239C missense unknown STK11 W239C lies within the protein kinase domain of the Stk11 protein. W239C has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
H174R missense loss of function - predicted STK11 H174R lies within the protein kinase domain of the Stk11 protein (UniProt.org). H174R is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
W308* nonsense no effect - predicted STK11 W308* results in a premature truncation of the Stk11 protein at amino acid 308 of 433 within the protein kinase domain (UniProt.org). W308* results in p53 activity similar to wild-type Stk11 as demonstrated by luciferase assay (PMID: 30092773), and therefore, is predicted to have no effect on Stk11 protein function.
Q37* nonsense loss of function - predicted STK11 Q37* results in a premature truncation of the Stk11 protein at amino acid 37 of 433 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), Q37* is predicted to lead to a loss of Stk11 protein function.
S216F missense loss of function - predicted STK11 S216F lies within the protein kinase domain of the Stk11 protein (UniProt.org). S216F is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
D176H missense unknown STK11 D176H lies within the protein kinase domain of the Stk11 protein (UniProt.org). D176H has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
Q364K missense unknown STK11 Q364K does not lie within any known functional domains of the Stk11 protein (UniProt.org). Q364K has been identified in sequencing studies (PMID: 25855536), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
I303N missense unknown STK11 I303N lies within the protein kinase domain of the Stk11 protein (UniProt.org). I303N has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, May 2018).
K62* nonsense loss of function - predicted STK11 K62* results in a premature truncation of the Stk11 protein at amino acid 62 of 433 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), K62* is predicted to lead to a loss of Stk11 protein function.
L245F missense unknown STK11 L245F lies within the protein kinase domain of the Stk11 protein (UniProt.org). L245F has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
A377P missense unknown STK11 A377P does not lie within any known functional domains of the Stk11 protein (UniProt.org). A377P has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
amp none no effect STK11 amplification indicates an increased number of copies of the STK11 gene. However, the mechanism causing the increase is unspecified.
V66M missense no effect STK11 V66M lies within the protein kinase domain of the Stk11 protein (UniProt.org). V66M demonstrates complex formation and kinase activity similar to wild-type Stk11 in cell culture (PMID: 19892943).
G56Tfs*4 frameshift loss of function - predicted STK11 G56Tfs*4 indicates a shift in the reading frame starting at amino acid 56 and terminating 4 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, G56Tfs*4 is predicted to lead to a loss of Stk11 protein function.
D237Y missense unknown STK11 D237Y lies within the protein kinase domain of the Stk11 protein (UniProt.org). D237Y has not been characterized in the scientific literature and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
K62Sfs*100 frameshift loss of function - predicted STK11 K62Sfs*100 indicates a shift in the reading frame starting at amino acid 62 and terminating 100 residues downstream causing a premature truncation of the 433 amino acid Stk11 protein (UniProt.org). Due to the loss of a majority of the protein kinase domain, K62Sfs*100 is predicted to lead to a loss of Stk11 protein function.
E120* nonsense loss of function - predicted STK11 E120* results in a premature truncation of the Stk11 protein at amino acid 120 of 433 within the protein kinase domain (UniProt.org). Due to the loss of a majority of the protein kinase domain, E120* is predicted to lead to a loss of Stk11 protein function.
E223* nonsense unknown STK11 E223* results in a premature truncation of the Stk11 protein at amino acid 223 of 433 within the protein kinase domain (UniProt.org). E223* has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Apr 2018).
N181E missense loss of function - predicted STK11 N181E lies within the protein kinase domain of the Stk11 protein (UniProt.org). N181E is predicted to confer a loss of function to the Stk11 protein, as demonstrated by its inability to activate the downstream kinase, Ampk (PMID: 19892943).
wild-type none no effect Wild-type STK11 indicates that no mutation has been detected within the STK11 gene.
Molecular Profile Protein Effect Treatment Approaches
STK11 E33* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 K78E unknown
STK11 Q137* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Y36D unknown
STK11 H107L unknown
STK11 A241P unknown
STK11 S193F unknown
STK11 L282Afs*3 unknown
STK11 N181Y unknown
STK11 K48fs loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 P281L loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 L183V unknown
STK11 Q100* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 A389T unknown
STK11 P179S unknown
STK11 W308C loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D350E unknown
STK11 E357K unknown
STK11 R333C unknown
STK11 D194H unknown
STK11 K44* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 L195M unknown
STK11 E199* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D194Y loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 E199Q no effect - predicted
STK11 R297S unknown
STK11 E57Sfs*107 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q159* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 K41* loss of function - predicted
STK11 G196V unknown
STK11 S232P no effect
STK11 C278fs loss of function - predicted
STK11 P221L unknown
STK11 P179R unknown
STK11 P369S unknown
STK11 I111N unknown
STK11 D358N unknown
STK11 E57fs loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 S19P unknown
STK11 N181I unknown
STK11 E138* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q123R no effect
STK11 R304W loss of function mTOR Inhibitor mTORC1 Inhibitor
STK11 I177N loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 loss loss of function mTOR Inhibitor mTORC1 Inhibitor
ERBB2 act mut STK11 loss
PTEN loss STK11 loss
KRAS G12D STK11 loss
STK11 D194E STK11 loss
KRAS mut STK11 loss TP53 loss
STK11 Q170P loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D176Y loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D355N unknown
STK11 dec exp no effect
STK11 E121* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D277Y loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 G242W unknown
STK11 I35Lfs*127 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 G56V unknown
STK11 D194E loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 W332* unknown
STK11 D53Tfs*11 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 H168R unknown
STK11 P314H unknown
STK11 T250P loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 P179Q unknown
STK11 D176A unknown
STK11 G56W unknown
STK11 V236A unknown
STK11 E317K unknown
STK11 D237N unknown
STK11 D194N unknown
STK11 M136R loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q302* unknown
STK11 K78N unknown
STK11 E199K loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 L67P loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q37L unknown
STK11 T230P no effect
STK11 I248T unknown
STK11 R86G no effect
STK11 K78I loss of function mTOR Inhibitor mTORC1 Inhibitor
STK11 E223V loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 G242V unknown
STK11 G171S loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 H174Y unknown
STK11 F157S loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D343N unknown
STK11 L245R loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q123* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 L285Q loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 P294L unknown
STK11 V320fs unknown
STK11 G163D loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D176N loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 I303S unknown
STK11 E165* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 C132F unknown
STK11 I177T unknown
STK11 Y272H loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 E70* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
KRAS G12S STK11 inact mut
STK11 inact mut loss of function mTOR Inhibitor mTORC1 Inhibitor
KRAS mut STK11 inact mut
KRAS G12D STK11 inact mut
STK11 Y60* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 Q170* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 G61Afs*3 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
KRAS mut STK11 mut
STK11 mutant unknown
STK11 P281Rfs*6 unknown
STK11 P281fs loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 A205T loss of function mTOR Inhibitor mTORC1 Inhibitor
STK11 F354L loss of function mTOR Inhibitor mTORC1 Inhibitor
STK11 R304G unknown
STK11 H174D unknown
STK11 S419F unknown
STK11 Q214* loss of function - predicted
STK11 R310P unknown
STK11 G251V unknown
STK11 Q220* unknown
STK11 D359Y unknown
STK11 G251F unknown
STK11 K78A loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 W239C unknown
STK11 H174R loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 W308* no effect - predicted
STK11 Q37* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 S216F loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D176H unknown
STK11 Q364K unknown
STK11 I303N unknown
STK11 K62* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 L245F unknown
STK11 A377P unknown
STK11 amp no effect
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp
STK11 V66M no effect
STK11 G56Tfs*4 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 D237Y unknown
STK11 K62Sfs*100 loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 E120* loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 E223* unknown
STK11 N181E loss of function - predicted mTOR Inhibitor mTORC1 Inhibitor
STK11 wild-type no effect
EGFR wild-type STK11 wild-type TP53 mut
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
STK11 K48fs non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 K48fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 E199* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E199*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 E57fs non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E57fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 loss Advanced Solid Tumor no benefit Metformin Preclinical Actionable In a preclinical study, Glucophage (metformin) was unable to inhibit cancer cell growth in cancer cell lines with biallelic loss of STK11 (PMID: 17062558, 18006825). 18006825 17062558
STK11 loss lung cancer resistant unspecified PD-1 antibody Preclinical Actionable In a preclinical study, PD-1 antibodies were ineffective in treating Stk11 (also known as Lkb1) deficient lung tumors in mice (PMID: 26833127). 26833127
ERBB2 act mut STK11 loss breast cancer sensitive AZD8055 Preclinical Actionable In a preclinical study, AZD8055 inhibited tumor growth in a mouse model of spontaneous breast cancer harboring an ERBB2 (HER2) activating mutation and loss of STK11 (LKB1), which was enhanced by the addition of 2-DG (2-deoxyglucose) (PMID: 25436981). 25436981
PTEN loss STK11 loss endometrial cancer sensitive Pictilisib Preclinical Actionable In a preclinical study, the PI3K inhibitor GDC-0941 reduced tumor growth rate in immunodeficient mice engrafted with endometrial tumors from PTEN/STK11 (LKB1) deficient mice (PMID: 24322983). 24322983
KRAS G12D STK11 loss non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical Actionable In a preclinical study, MK-1775 and Platinol (cisplatin) combination treatment resulted in improved survival in transgenic animal models of non-small cell lung carcinoma harboring KRAS G12D and STK11 loss compared to Platinol (cisplatin) alone (PMID: 28652249). 28652249
STK11 D194E STK11 loss pancreatic cancer sensitive Everolimus Clinical Study Actionable In a clinical case study, a pancreatic cancer patient with Peutz-Jeghers syndrome harboring STK11 D194E and loss of heterozygosity of the other STK11 allele in the tumor achieved a partial response following treatment with Afinitor (everolimus), but progressed after 9 months (PMID: 21189378). 21189378
KRAS mut STK11 loss TP53 loss non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring KRAS mutation, STK11 and TP53 loss demonstrated increased sensitivity to MK-1775 and Platinol (cisplatin) combination treatment in culture compared to isogenic cell lines expressing wild-type Tp53 or Stk11 (PMID: 28652249). 28652249
STK11 dec exp non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, knockdown of STK11 increased sensitivity to Mekinist (trametinib) in non-small cell lung cancer cell lines in culture and in xenograft models (PMID: 27821489). 27821489
STK11 W332* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 W332*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
KRAS G12S STK11 inact mut non-small cell lung carcinoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a human non-small cell lung cancer cell line harboring KRAS G12S and an STK11(LKB) inactivating mutation (PMID: 25637314). 25637314
STK11 inact mut Advanced Solid Tumor sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to PD-0325901 in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 inact mut pituitary carcinoma sensitive Everolimus + Radiotherapy Clinical Study Actionable In a clinical case study, a patient with adenocorticotropic pituitary carcinoma harboring an STK11 inactivating mutation demonstrated clinical efficacy for greater than 6 months when treated with a combination of Afinitor (everolimus) and radiotherapy (PMID: 27615706). 27615706
STK11 inact mut Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlated to STK11 inactivating mutations, was associated with increased sensitivity to Mekinist (trametinib) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 inactivating mutation and STK11 loss expression signature was associated with increased sensitivity to Selumetinib (AZD6244) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut Advanced Solid Tumor sensitive CI-1040 Preclinical - Cell culture Actionable In a preclinical study, the presence an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to CI-1040 (PD184352) in human tumor cell lines in culture (PMID: 27821489). 27821489
STK11 inact mut endometrial cancer sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) reduced S6K phosphorylation and inhibited tumor growth in mouse models of STK11 (LKB1)-deficient endometrial cancer, including models with advanced tumors (PMID: 20142330). 20142330
STK11 inact mut Advanced Solid Tumor sensitive RDEA119 Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to RDEA119 in human tumor cell lines in culture (PMID: 27821489). 27821489
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive Adavosertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations demonstrated increased sensitivity to MK-1775 compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut non-small cell lung carcinoma sensitive SAR245409 Preclinical - Cell line xenograft Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring a KRAS mutation and STK11 inactivating mutation was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in cell line xenograft models (PMID: 24634413). 24634413
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical - Cell culture Actionable In a preclinical study, MK-1775 and Platinol (cisplatin) combination treatment demonstrated enhanced growth inhibition in non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive MK-1775 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, MK-1775 combined with radiation therapy demonstrated enhanced growth inhibition in non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut lung adenocarcinoma sensitive MLN0128 + Phenformin Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) in combination with phenformin induced apoptosis and energetic stress in human lung adenocarcinoma cell lines with concurrent KRAS and STK11 (LKB1) mutations in culture, with higher levels than either therapy as a single agent (PMID: 26574479). 26574479
KRAS G12D STK11 inact mut lung cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) inhibited lung tumor growth in mouse models with KRAS G12D and inactivation of STK11 (LKB1), and demonstrated limited efficacy in tumors with KRAS G12D and wild-type STK11 (PMID: 26574479). 26574479
KRAS mut STK11 mut lung adenocarcinoma predicted - resistant unspecified PD-1 antibody Clinical Study Actionable In a clinical study, lung adenocarcinoma patients co-harboring a KRAS mutation and STK11 mutation demonstrated a lower objective response rate (7.4% vs 35.7% vs 28.6%) and shorter PFS (1.8mo vs 3.0 vs 2.7) and OS (6.4mo vs 16 vs 16.1) compared to patients with KRAS and TP53 mutations and patients with KRAS mutations only when treated with a PD-1 inhibitor (Nivolumab, n=146; Pembrolizumab, n=19) (PMID: 29773717). 29773717
KRAS mut STK11 mut non-small cell lung carcinoma predicted - resistant unspecified PD-1 antibody Phase III Actionable In a Phase III trial, non-small cell lung carcinoma patients co-harboring a KRAS mutation and STK11 mutation demonstrated an objective response rate (ORR) of 0% (0/6) when treated with Opdivo (nivolumab) compared to an ORR of 57.1% (4/7) in patients co-harboring a KRAS mutation and TP53 mutation and an ORR of 18.2% (2/11) in patients with mutant KRAS only (PMID: 29773717; NCT01673867). 29773717
KRAS mut STK11 mut non-small cell lung carcinoma sensitive PKI-402 Preclinical - Cell line xenograft Actionable In a preclinical study, PKI-402 inhibited growth of a non-small cell lung cancer cell line harboring both KRAS and STK11 mutations in culture and in cell line xenograft models (PMID: 20371716). 20371716
STK11 mutant pancreatic cancer not applicable N/A Guideline Risk Factor Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org). detail...
STK11 mutant non-small cell lung carcinoma decreased response Nivolumab Clinical Study Actionable In a clinical study, mutant STK11 correlated with a worse response to Opdivo (nivolumab) compared to wild-type STK11 in non-small cell lung carcinoma patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 1138PD). detail...
STK11 mutant non-small cell lung carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PF-05212384) inhibited growth of human non-small cell lung carcinoma cells harboring an STK11 mutation in culture (PMID: 21325073). 21325073
STK11 mutant stomach cancer not applicable N/A Guideline Risk Factor Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing gastric cancer (NCCN.org). detail...
STK11 F354L triple-receptor negative breast cancer sensitive Exemestane + Everolimus Clinical Study Actionable In a clinical case study, Afinitor (everolimus) in combination with Aromasin (exemestane) resulted in complete response ongoing for 14 months in a patient with metastatic triple-receptor negative breast cancer harboring STK11 F354L (PMID: 28550065). 28550065
STK11 Q37* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 Q37*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). 29636358
STK11 wild-type Advanced Solid Tumor sensitive Metformin Preclinical Actionable In a preclinical studies, Glucophage (metformin) inhibited cancer cell growth by activating the AMP kinase pathway in a variety of cancer cell lines that retained one functional allele of STK11 (PMID: 17062558, 18006825). 18006825 17062558
EGFR wild-type STK11 wild-type TP53 mut non-small cell lung carcinoma predicted - sensitive Pembrolizumab Clinical Study Actionable In a retrospective analysis, a genomic profile consisted of mutant TP53, wild-type STK11 and EGFR is associated with increased PD-L1 expression and improved progression-free survival in Keytruda (pembrolizumab)-treated non-small cell lung cancer patients (PMID: 29764856). 29764856
EGFR wild-type STK11 wild-type TP53 mut non-small cell lung carcinoma predicted - sensitive Nivolumab Clinical Study Actionable In a retrospective analysis, a genomic profile consisted of mutant TP53, wild-type STK11 and EGFR is associated with increased PD-L1 expression and improved progression-free survival in Opdivo (nivolumab)-treated non-small cell lung cancer patients (PMID: 29764856). 29764856