Gene Detail

Gene Symbol MAP2K1
Synonyms CFC3 | MAPKK1 | MEK1 | MKK1 | PRKMK1
Gene Description MAP2K1 (MEK1), mitogen-activated protein kinase kinase 1, is a serine-threonine kinase, which activates that RAS-RAF-MEK-ERK pathway in cell proliferation and differentiation (PMID: 22753777). MAP2K1 (MEK1) activating mutations have been identified in a number of solid tumor types including, melanoma (PMID: 29753091), colorectal (PMID: 28819429), lung adenocarcinoma (PMID: 25351745), histiocytic sarcoma (PMID: 29768143), and Map2k1 mutations are often associated with resistance to Mek and Raf inhibition (PMID: 29753091).
Entrez Id 5604
Chromosome 15
Map Location 15q22.31
Canonical Transcript NM_002755

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
I204T missense gain of function MAP2K1 I204T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I204T confers a gain of function to the Map2k1 protein as indicated by transformation activity and increased phosphorylation of Erk1/2 in culture (PMID: 22327936).
S123T missense gain of function MAP2K1 S123T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S123T confers a gain of function to the Map2k1 protein as demonstrated by increased Mek and Erk phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
R349K missense unknown MAP2K1 R349K lies within the protein kinase domain of the Map2k1 protein (UniProt.org). R349K has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
G128D missense gain of function - predicted MAP2K1 G128D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128D is predicted to confer a gain of function to the Map2k1 protein as indicated by increased phosphorylation of downstream targets (PMID: 28115009).
E51_Q58del deletion gain of function MAP2K1 E51_Q58del results in the deletion of eight amino acids in the Map2k1 protein from amino acids 51 to 58 (UniProt.org). E51_Q58del results in activation of Map2k1 as indicated by increased Erk and Mek phosphorylation in cell culture (PMID: 29483135).
R47Q missense gain of function MAP2K1 R47Q does not lie within any known functional domains of the Map2k1 protein (UniProt.org). R47Q results in increased phosphorylation of Erk and is transforming in cell culture (PMID: 22327936).
G79V missense unknown MAP2K1 G79V lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G79V has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
T28I missense gain of function - predicted MAP2K1 T28I lies within the Erk binding domain of the Map2k1 protein (PMID: 26566875). T28I is predicted to confer a gain of function to the Map2k1 protein as demonstrated by increased Mek phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
C121S missense gain of function MAP2K1 C121S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). C121S confers a gain of function on the Map2k1 protein as demonstrated by increased Erk1/2 (PMID: 25899310) and Mek phosphorylation in culture and has been demonstrated to confer acquired resistance to Raf and Mek inhibitors (PMID: 21383288, PMID: 24448821, PMID: 29483135, PMID: 29753091). Y
K57N missense gain of function MAP2K1 K57N does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K57N confers a gain of function on the Map2k1 protein as demonstrated by increased autophosphorylation (PMID: 29753091), increased Erk phosphorylation (PMID: 18632602, PMID: 29753091), increased cell proliferation and cell viability as compared to wild-type Map2k1, in two different cell lines (PMID: 29533785, PMID: 18632602), and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). Y
I111N missense gain of function - predicted MAP2K1 I111N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I111N is predicted to confer a gain of function to the Map2k1 protein, as demonstrated by increased Map2k1 kinase activity in an in-vitro assay and is also associated with resistance to inhibitors (PMID: 12370306). Y
Y130H missense no effect - predicted MAP2K1 Y130H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y130H has been demonstrated to have autohphosphorylation levels similar to wild-type Map2k1 in an in-vitro assay (PMID: 29753091) and therefore, is predicted to have no effect on Map2k1 protein function.
D351G missense unknown MAP2K1 D351G lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D351G has been identified in the scientific literature (PMID: 26582713, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
E102_I103del deletion gain of function MAP2K1 E102_I103del results in the deletion of two amino acids in the protein kinase domain of the Map2k1 protein from amino acids 102 to 103 (UniProt.org). E102_I103del confers a gain of function to the Map2k1 protein as demonstrated by activity independent of Raf and increased phosphorylation of Mek and Erk relative to wild-type Map2k1 in vitro (PMID: 29483135).
A132V missense unknown MAP2K1 A132V lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A132V has been identified in sequencing studies (PMID: 22895193, PMID: 25839328), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
D136Y missense unknown MAP2K1 D136Y lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D136Y has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
P306H missense gain of function MAP2K1 P306H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P306H confers a gain of function to the Map2k1 protein as indicated by increased phosphorylation of Erk1/2 and modest transformation activity in culture (PMID: 22327936).
L115R missense unknown MAP2K1 L115R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L115R has been described as a drug resistance mutation (PMID: 19915144), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jul 2018). Y
R96K missense unknown MAP2K1 R96K lies within the protein kinase domain of the Map2k1 protein (UniProt.org). R96K has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
E333A missense unknown MAP2K1 E333A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E333A has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
F53_Q58del deletion gain of function MAP2K1 F53_Q58del results in the deletion of six amino acids in the Map2k1 protein from amino acids 53 to 58 (UniProt.org). F53_Q58del results in activation of Map2k1 as indicated by increased Erk and Mek phosphorylation in cell culture (PMID: 25164765, PMID: 29483135).
P323A missense unknown MAP2K1 P323A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P323A has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
H119Q missense unknown MAP2K1 H119Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). H119Q has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
P124L missense gain of function MAP2K1 P124L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124L confers a gain of function on the Map2k1 protein as demonstrated by increased Erk 1/2 phosphorylation (PMID: 19915144, PMID: 29483135) and Mek phosphorylation in cultured cells (PMID: 29483135) and also confers resistance to some Mek and Braf inhibitors in melanoma cells (PMID: 19915144). Y
S123P missense unknown MAP2K1 S123P lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S123P has been identified in the scientific literature (PMID: 26566875), but has not been characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
F53I missense unknown MAP2K1 F53I does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53I has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
I111R missense gain of function - predicted MAP2K1 I111R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I111R is predicted to confer a gain of function to the Map2k1 protein, as demonstrated by increased Map2k1 kinase activity in an in-vitro assay and is also associated with resistance to inhibitors (PMID: 12370306). Y
R108Q missense unknown MAP2K1 R108Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). R108Q has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
E144K missense gain of function MAP2K1 E144K lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E144K confers a gain of function to the Map2k1 protein as demonstrated by increased Mek and Erk phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
D65N missense gain of function - predicted MAP2K1 D65N lies adjacent to the protein kinase domain of the Map2k1 protein (UniProt.org). D65N is predicted to confer a gain of function to the Map2k1 protein as demonstrated by increased Mek phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
H119P missense unknown MAP2K1 H119P lies within the protein kinase domain of the Map2k1 protein (UniProt.org). H119P has been described as a drug resistance mutation (PMID: 19915144), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jul 2018). Y
F53V missense unknown MAP2K1 F53V does not lie within any know functional domains of the Map2k1 protein (UniProt.org). F53V has been identified in the scientific literature (PMID: 27511764), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
I310L missense unknown MAP2K1 I310L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I310L has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
R49C missense unknown MAP2K1 R49C does not lie within any known functional domains of the Map2k1 protein (UniProt.org). R49C has been identified in the scientific literature (PMID: 24982505), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
M146I missense unknown MAP2K1 M146I lies within the protein kinase domain of the Map2k1 protein (UniProt.org). M146I has been identified in the scientific literature (PMID: 25351745, PMID: 22980975, PMID: 26582713), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
V258I missense unknown MAP2K1 V258I lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V258I has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
L37P missense gain of function MAP2K1 L37P lies within the nuclear export region of the Map2k1 protein (PMID: 26566875). L37P confers a gain of function to the Map2k1 protein as demonstrated by increased Mek and Erk phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
K57E missense gain of function MAP2K1 K57E does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K57E confers a gain of function on the Map2k1 protein as demonstrated by increased activation of downstream Erk1/2 and has been associated with Braf inhibitor resistance in cell culture (PMID: 24463458, PMID: 25370473). Y
D351N missense unknown MAP2K1 D351N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D351N has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
G128N missense no effect - predicted MAP2K1 G128N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128N has been demonstrated to have autophosphorylation levels similar to wild-type Map2k1 in an in-vitro assay (PMID: 29753091) and therefore, is predicted to have no effect on Map2k1 protein function.
A106T missense no effect - predicted MAP2K1 A106T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A106T demonstrates phosphorylation of Erk similar to wild-type Map2k1 in cell culture (PMID: 25164765) and therefore, is predicted to have no effect on Map2k1 protein function.
E320A missense unknown MAP2K1 E320A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E320A has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
E203K missense gain of function MAP2K1 E203K lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E203K results in constitutive phosphorylation of Erk, is transforming in cell culture (PMID: 22197931, PMID: 29483135), and increases autophosphorylation of Map2k1 (PMID: 29753091).
K97M missense loss of function MAP2K1 K97M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). K97M is referred to as a kinase dead variant and does not result in phosphorylation of Erk1/2 and therefore, confers a loss of function to the Map2k1 protein (PMID: 15342384).
P387S missense gain of function MAP2K1 P387S does not lie within any known functional domains of the Map2k1 protein (UniProt.org). P387S confers a gain of function to the Map2k1 protein as demonstrated by constitutive phosphorylation of Mek and Erk (PMID: 22389471).
T55P missense no effect - predicted MAP2K1 T55P does not lie within any known functional domains of the Map2k1 protein (UniProt.org). T55P has been demonstrated to have autophosphorylation levels similar to wild-type Map2k1 in an in vitro assay (PMID: 29753091) and therefore, is predicted to have no effect on Map2k1 protein function.
R49L missense gain of function MAP2K1 R49L does not lie within any known functional domains of the Map2k1 protein (UniProt.org). R49L confers a gain of function to the Map2k1 protein as demonstrated by transforming ability in culture and in vivo, and phosphorylation of Erk1/2 (PMID: 22327936).
D336H missense unknown MAP2K1 D336H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D336H has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
N382H missense unknown MAP2K1 N382H does not lie within any known functional domains of the Map2k1 protein (UniProt.org). N382H has not been fully biochemically characterized, however, did not result in Erk phosphorylation in culture (PMID: 22197931).
L115P missense gain of function MAP2K1 L115P lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L115P confers a gain of function on the kinase activity of the Map2k1 protein, as demonstrated by increased autophosphorylation (PMID: 29753091) and increased basal kinase activity (PMID: 12370306), and is also associated with decreased binding and resistance to Mek inhibitors (PMID: 12370306, PMID: 19915144, PMID: 26399658). Y
K57C missense gain of function - predicted MAP2K1 K57C does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K57C has not been biochemically characterized, however, results in restored pathway activation in the presence of an upstream pathway inhibitor and therefore, is predicted to result in a gain of Map2k1 protein function (PMID: 24463458).
A158T missense unknown MAP2K1 A158T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A158T has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
A76fs frameshift loss of function - predicted MAP2K1 A76fs results in a change in the amino acid sequence of the Map2k1 protein beginning at aa 76 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), A76fs is predicted to result in a loss of Map2k1 function.
G80S missense unknown MAP2K1 G80S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G80S has been identified in sequencing studies (PMID: 25344691), but has not been biochemically characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
S218D missense gain of function MAP2K1 S218D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S218D confers a gain of function to the Map2k1 protein as indicated by increased Map2k1 activity in the absence of growth factor, cell growth in culture, and tumor formation in mouse models (PMID: 7936666).
R201C missense unknown MAP2K1 R201C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). R201C has been identified in sequencing studies (PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
K4N missense unknown MAP2K1 K4N does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K4N has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
Q56P missense gain of function MAP2K1 Q56P does not lie within any known functional domains of the Map2k1 protein (UniProt.org). Q56P confers a gain of function to the Map2k1 protein as indicated by increased kinase activity and the ability to transform cultured cells (PMID: 22327936, PMID: 7651428) and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). Y
G128V missense no effect - predicted MAP2K1 G128V lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128V has been demonstrated to have autophosphorylation levels similar to wild-type Map2k1 in an in vitro assay (PMID: 29753091) and has also been described as a drug resistance mutation (PMID: 24265153). Y
L235H missense unknown MAP2K1 L235H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L235H has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
G128C missense unknown MAP2K1 G128C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128C has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
E203Q missense no effect MAP2K1 E203Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E203Q has been demonstrated to have autohphosphorylation and kinase activities similar to wild-type Map2k1 in in vitro assays (PMID: 29753091).
S327T missense unknown MAP2K1 S327T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S327T has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
Q56_V60del deletion gain of function MAP2K1 Q56_V60del results in the deletion of five amino acids in the protein kinase domain of the Map2k1 protein from amino acids 56 to 60 (UniProt.org). Q56_V60del confers a gain of function to the Map2k1 protein as indicated by transformation capabilities and increased phosphorylation of Erk and S6k in culture (PMID: 26324360).
F68L missense unknown MAP2K1 F68L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). F68L has been identified in the scientific literature (PMID: 26566875), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
E44G missense no effect MAP2K1 E44G does not lie within any known functional domains of the Map2k1 protein (UniProt.org). E44G does not result in constitutive and ligand-independent activation of Map2k1 or activation of Erk at levels different than wild-type Map2k1 (PMID: 28166211).
P124S missense unknown MAP2K1 P124S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). The functional effect of P124S is conflicting, as P124S has been reported to confer a gain of function on the Map2k1 protein as demonstrated by increased ERK1/2 phosphorylation, but has similar induction of cell proliferation and viability levels as wild-type Map2k1 (PMID: 29533785), and also confers resistance to Mek and Braf inhibitors in melanoma cells (PMID: 19915144, PMID: 22197931), Y
V60E missense unknown MAP2K1 V60E does not lie within any known functional domains of the Map2k1 protein (UniProt.org). V60E has been described as a drug resistance mutation (PMID: 24265153), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jul 2018). Y
K57T missense unknown MAP2K1 K57T lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). K57T has been demonstrated to occur as a secondary drug resistance mutation (PMID: 26644315, PMID: 28819429), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018). Y
I99_K104del deletion gain of function MAP2K1 I99_K104del results in the deletion of six amino acids in the Map2k1 protein from amino acids 99 to 104 (UniProt.org). I99_K104del confers a gain of function to the Map2k1 protein as demonstrated by activity, independent of Raf, and increased phosphorylation of Mek and Erk relative to wild-type Map2k1 in vitro (PMID: 29483135).
I103N missense gain of function - predicted MAP2K1 I103N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I103N is predicted to confer a gain of function on the Map2k1 protein as demonstrated by increased Map2k1 autophosphorylation in cell culture (PMID: 29753091) and is also associated with resistance to Mek inhibitors (PMID: 12370306, PMID: 19915144). Y
S86A missense unknown MAP2K1 S86A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S86A has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
K35N missense unknown MAP2K1 K35N does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K35N has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
amp none no effect MAP2K1 amp indicates an increased number of copies of the MAP2K1 gene. However, the mechanism causing the increase is unspecified.
D190Y missense unknown MAP2K1 D190Y lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D190Y has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
I111P missense gain of function - predicted MAP2K1 I111P lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I111P is predicted to confer a gain of function to the Map2k1 protein, as demonstrated by increased Map2k1 kinase activity in an in-vitro assay and is also associated with resistance to inhibitors (PMID: 12370306). Y
C121G missense unknown MAP2K1 C121G lies within the protein kinase domain of the Map2k1 protein (UniProt.org). C121G has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
S331R missense unknown MAP2K1 S331R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S331R has been identified in the scientific literature (PMID: 25351745, PMID: 26582713), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
Y130N missense no effect - predicted MAP2K1 Y130N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y130N has been demonstrated to have autohphosphorylation levels similar to wild-type Map2k1 in an in-vitro assay (PMID: 29753091) and therefore, is predicted to have no effect on Map2k1 protein function.
act mut unknown gain of function MAP2K1 act mut indicates that this variant results in a gain of function in the Map2k1 protein. However, the specific amino acid change has not been identified.
G128R missense unknown MAP2K1 G128R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128R has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
R260M missense unknown MAP2K1 R260M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). R260M has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
S222A missense no effect - predicted MAP2K1 S222A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S222A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Map2k1 (PMID: 29533785) and therefore, is predicted to have no effect on Map2k1 protein function.
F53C missense unknown MAP2K1 F53C does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53C has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
K59del deletion unknown MAP2K1 K59del results in the deletion of amino acid 59 within the protein kinase domain of the Map2k1 protein (UniProt.org). K59del may confer a gain of function the the Map2k1 protein as demonstrated by elevated Mek and Erk phosphorylation (PMID: 22389471), however, in another study, K59del had autophosphorylation levels similar to wild-type Map2k1 (PMID: 29753091).
L115A missense gain of function - predicted MAP2K1 L115A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L115A is predicted to confer a gain of function to the Map2k1 protein, as demonstrated in an in-vitro kinase assay (PMID: 12370306) and is also associated with decreased binding and partial response to Mek inhibitors (PMID: 12370306).
F129L missense gain of function MAP2K1 F129L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). F129L confers a gain of function to the Map2k1 protein as demonstrated by increased kinase activity compared to wild-type, activation of downstream Erk signaling, and increased binding affinity to c-Raf (PMID: 21705440) and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). Y
F53_Q58delinsL indel unknown MAP2K1 F53_Q58delinsL results in a deletion of six amino acids of the Map2k1 protein from amino acids 53 to 58, combined with the insertion of a leucine (L) at the same site (UniProt.org). F53_Q58delinsL has been identified in the scientific literature (PMID: 24982505), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
A76T missense unknown MAP2K1 A76T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A76T has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
G294E missense unknown MAP2K1 G294E lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G294E has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
L177M missense unknown MAP2K1 L177M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L177M has been identified in the scientific literature (PMID: 25351745), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
L42F missense no effect MAP2K1 L42F does not lie within any known functional domains of the Map2k1 protein (UniProt.org). L42F has been demonstrated to have autohphosphorylation and kinase activities similar to wild-type Map2k1 in in vitro assays (PMID: 29753091).
F53Y missense unknown MAP2K1 F53Y does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53Y has been identified in the scientific literature (PMID: 27325104, PMID: 24265153, PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
Y134C missense unknown MAP2K1 Y134C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y134C has been identified in sequencing studies (PMID: 26582713) but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
V224M missense unknown MAP2K1 V224M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V224M has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018)
D67N missense gain of function MAP2K1 D67N does not lie within any known functional domains of the Map2k1 protein (UniProt.org). D67N results in constitutive activation of Erk signaling in cell culture (PMID: 25049390) and slightly increased Erk and Mek phosphorylation in cell culture (PMID: 29483135).
F53L missense gain of function MAP2K1 F53L does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53L results in activation of Map2k1 as indicated by increased Erk and Mek phosphorylation in cell culture (PMID: 25164765, PMID: 29483135) and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). Y
L98_K104delinsQ indel gain of function MAP2K1 L98_K104delinsQ results in a deletion of seven amino acids in the Map2k1 protein combined with the insertion of one new amino acid in the same location (UniProt.org). L98_K104delinsQ results in increased activation of Map2k1 and elevated phosphorylation of Mapk1 in-vitro (PMID: 29768711), and has also been demonstrated to occur as a putative drug resistance mutation (PMID: 29768711). Y
L98_I103del deletion gain of function MAP2K1 L98_I103del results in the deletion of six amino acids in the Map2k1 protein from amino acids 98 to 103 (UniProt.org). L98_I103del confers a gain of function to the Map2k1 protein as demonstrated by activity independent of Raf and increased phosphorylation of Mek and Erk relative to wild-type Map2k1 in vitro (PMID: 29483135).
P162S missense unknown MAP2K1 P162S lies within the protein kinase domain of the Map2k2 protein (UniProt.org). P162S has been identified in the scientific literature (PMID: 24265154), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, May 2018).
A390T missense unknown MAP2K1 A390T does not lie within any known functional domains of the Map2k1 protein (UniProt.org). A390T has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
H119Y missense unknown MAP2K1 H119Y lies within the protein kinase domain of the Map2k1 protein (UniProt.org). H119Y has been identified in the scientific literature (PMID: 26582713, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
I103_K104del deletion gain of function MAP2K1 I103_K104del results in the deletion of two amino acids in the Map2k1 protein from amino acids 103 to 104 (UniProt.org). I103_K104del confers a gain of function to the Map2k1 protein as demonstrated by activity independent of Raf and increased phosphorylation of Mek and Erk relative to wild-type Map2k1 in vitro (PMID: 29483135).
V211D missense gain of function MAP2K1 V211D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V211D confers a gain of function on the Map2k1 protein as demonstrated by increased autophosphorylation and Erk phosphorylation and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091, PMID: 19915144). Y
Q58_E62del deletion gain of function MAP2K1 Q58_E62del results in the deletion of five amino acids in the Map2k1 protein from amino acis 58 to 62 (UniProt.org). Q58_E62del confers a gain of function to the Map2k1 protein as demonstrated by increased Mek and Erk phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
I111A missense gain of function - predicted MAP2K1 I111A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I111A is predicted to confer a gain of function to the Map2k1 protein, as demonstrated by increased Map2k1 kinase activity in an in-vitro assay and is also associated with resistance to inhibitors (PMID: 12370306). Y
Y130C missense unknown MAP2K1 Y130C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). The functional effect of Y130C is conflicting, as Y130C has been reported to confer a gain of function to the Map2k1 protein function as indicated by increased Erk phosphorylation in cell culture (PMID: 16439621), however, in another study, Y130C had autohphosphorylation levels similar to wild-type Map2k1 in an in-vitro assay (PMID: 29753091).
V60M missense gain of function MAP2K1 V60M does not lie within any known functional domains of the Map2k1 protein (UniProt.org). V60M confers a gain of function to the Map2k1 protein as demonstrated by increased Mek and Erk phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
wild-type none no effect Wild-type MAP2K1 indicates that no mutation has been detected within the MAP2K1 gene.
G294R missense unknown MAP2K1 G294R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G294R has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
Q354H missense unknown MAP2K1 Q354H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Q354H has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
I9Sfs*3 frameshift loss of function - predicted MAP2K1 I9Sfs*3 indicates a shift in the reading frame starting at amino acid 9 and terminating 3 residues downstream causing a premature truncation of the 393 amino acid Map2k1 protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), I9Sfs*3 is predicted to lead to a loss of Map2k1 protein function.
mutant unknown unknown MAP2K1 mutant indicates an unspecified mutation in the MAP2K1 gene.
V93F missense unknown MAP2K1 V93F lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V93F has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
V211A missense unknown MAP2K1 V211A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V211A has not been characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
G301* nonsense unknown MAP2K1 G301* results in a premature truncation of the Map2k1 protein at amino acid 301 of 393 (UniProt.org). G301* lies within the RAF1-binding region, however, it has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (UniProt.org, PubMed, Jun 2018).
P193S missense unknown MAP2K1 P193S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P193S has been identified in sequencing studies (PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
N122D missense unknown MAP2K1 N122D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). N122D has been identified in the scientific literature (PMID: 21383288), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
F53S missense unknown MAP2K1 F53S does not lie within any known functional domains of the Map2k1 protein (UniProt.org). The functional effect of F53S is conflicting, as F53S has been reported to confer a gain of function to the Map2k1 protein as indicated by Erk phosphorylation greater than that induced by wild-type, but not as active as other constitutively active Map2k1 mutants in culture (PMID: 16439621, PMID: 12370306) and in another study, F53S had autophosphorylation levels similar to wild-type Map2k1 (PMID: 29753091).
S222D missense unknown MAP2K1 S222D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S222D has not been individually characterized, however, when combined with MAP2K1 S218D or MAP2K1 S226D, the combination results in constitutive activation of Map2k1 in culture (PMID: 7936666, PMID: 12506122).
P124Q missense unknown MAP2K1 P124Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124Q leads to increased Map2k1 activity, as demonstrated by increased activation of downstream Erk1/2 in cell culture (PMID: 25370473), however, in another study, P124Q has been demonstrated to have autohphosphorylation and kinase activities similar to wild-type Map2k1 in in vitro assays (PMID: 29753091).
P264S missense unknown MAP2K1 P264S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P264S has been identified in the scientific literature (PMID: 25351745, PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
A347T missense unknown MAP2K1 A347T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A347T has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jun 2018).
L177V missense unknown MAP2K1 L177V lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L177V has not been fully biochemically characterized, however, resulted in weak phosphorylation of Erk and Mek in vitro (PMID: 29483135) and therefore, its effect on Map2k1 protein function is unknown (PubMed, May 2018).
E120Q missense gain of function - predicted MAP2K1 E120Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). E120Q is predicted to confer a gain of function to the Map2k1 protein as demonstrated by increased Mek phosphorylation relative to wild-type Map2k1 (PMID: 26566875).
I111S missense gain of function MAP2K1 I111S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I111S confers a gain of function on the Map2k1 protein as demonstrated by increased autophosphorylation and Erk phosphorylation and also demonstrates resistance to some Mek and Braf inhibitors (PMID: 29753091). Y
W247* nonsense unknown MAP2K1 W247* results in a premature truncation of the Map2k1 protein at amino acid 247 of 393 (UniProt.org). W247* has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Jan 2018).
Molecular Profile Protein Effect Treatment Approaches
MAP2K1 I204T gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 S123T gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 R349K unknown
MAP2K1 G128D gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 E51_Q58del gain of function
MAP2K1 R47Q gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 G79V unknown
MAP2K1 T28I gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor
BRAF V600E MAP2K1 C121S
MAP2K1 C121S gain of function
EML4-ALK MAP2K1 K57N
ALK rearrange MAP2K1 K57N
MAP2K1 K57N gain of function MEK inhibitor (Pan) MEK1 Inhibitor
BRAF V600E MAP2K1 I111N
MAP2K1 I111N gain of function - predicted
MAP2K1 Y130H no effect - predicted
MAP2K1 D351G unknown
MAP2K1 Q56P MAP2K1 H119Y MAP2K1 D351G EGFR G719S
MAP2K1 E102_I103del gain of function
MAP2K1 A132V unknown
MAP2K1 D136Y unknown
MAP2K1 P306H gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 L115R unknown
MAP2K1 R96K unknown
MAP2K1 E333A unknown
MAP2K1 F53_Q58del gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 P323A unknown
MAP2K1 H119Q unknown
BRAF V600K MAP2K1 P124L
MAP2K1 P124L gain of function
BRAF V600E MAP2K1 P124L
MAP2K1 S123P unknown
MAP2K1 F53I unknown
MAP2K1 I111R gain of function - predicted
MAP2K1 R108Q unknown
MAP2K1 E144K gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 D65N gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 H119P unknown
BRAF V600E MAP2K1 H119P
MAP2K1 F53V unknown
MAP2K1 I310L unknown
MAP2K1 R49C unknown
MAP2K1 M146I unknown
MAP2K1 V258I unknown
MAP2K1 L37P gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 K57E gain of function
BRAF V600E MAP2K1 K57E
MAP2K1 D351N unknown
MAP2K1 G128N no effect - predicted
MAP2K1 A106T no effect - predicted
MAP2K1 E320A unknown
BRAF V600E MAP2K1 E203K
MAP2K1 E203K gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 K97M loss of function
BRAF V600E MAP2K1 P387S NRAS Q61K
BRAF V600E NRAS A146T MAP2K1 P387S
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S
MAP2K1 P387S gain of function
MAP2K1 T55P no effect - predicted
MAP2K1 R49L gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 D336H unknown
MAP2K1 N382H unknown
BRAF V600E MAP2K1 L115P
MAP2K1 L115P gain of function
MAP2K1 K57C gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 A158T unknown
MAP2K1 A76fs loss of function - predicted
MAP2K1 G80S unknown
MAP2K1 S218D gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 R201C unknown
MAP2K1 K4N unknown
MAP2K1 Q56P BRAF V600E
BRAF V600E MAP2K1 Q56P
MAP2K1 Q56P gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 G128V no effect - predicted
BRAF V600E MAP2K1 G128V
MAP2K1 L235H unknown
MAP2K1 G128C unknown
MAP2K1 E203Q no effect
MAP2K1 S327T unknown
MAP2K1 Q56_V60del gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 F68L unknown
MAP2K1 E44G no effect
BRAF V600E MAP2K1 P124S
MAP2K1 P124S unknown
MAP2K1 V60E unknown
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R
BRAF V600E MAP2K1 V60E
MAP2K1 K57T unknown
MAP2K1 I99_K104del gain of function
BRAF V600E MAP2K1 I103N
MAP2K1 I103N gain of function - predicted
MAP2K1 S86A unknown
MAP2K1 K35N unknown
MAP2K1 amp no effect MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 D190Y unknown
MAP2K1 I111P gain of function - predicted
MAP2K1 C121G unknown
MAP2K1 S331R unknown
MAP2K1 Y130N no effect - predicted
MAP2K1 act mut gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 G128R unknown
MAP2K1 R260M unknown
MAP2K1 S222A no effect - predicted
MAP2K1 F53C unknown
BRAF V600E MAP2K1 K59del
MAP2K1 K59del unknown MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 L115A gain of function - predicted
MAP2K1 F129L gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 F53_Q58delinsL unknown
MAP2K1 A76T unknown
MAP2K1 G294E unknown
MAP2K1 L177M unknown
MAP2K1 L42F no effect
MAP2K1 F53Y unknown
MAP2K1 Y134C unknown
MAP2K1 Y134C KRAS Q61H
MAP2K1 V224M unknown
MAP2K1 D67N gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 F53L gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 L98_K104delinsQ gain of function
MAP2K1 L98_I103del gain of function
BRAF V600E MAP2K1 P162S
MAP2K1 P162S unknown
MAP2K1 A390T unknown
MAP2K1 H119Y unknown
MAP2K1 I103_K104del gain of function
BRAF V600E MAP2K1 V211D
MAP2K1 V211D gain of function
MAP2K1 Q58_E62del gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 I111A gain of function - predicted
MAP2K1 Y130C unknown MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 V60M gain of function MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 wild-type no effect
MAP2K1 G294R unknown
MAP2K1 Q354H unknown
MAP2K1 I9Sfs*3 loss of function - predicted
MAP2K1 mutant unknown
MAP2K1 V93F unknown
MAP2K1 V211A unknown
MAP2K1 G301* unknown
MAP2K1 P193S unknown
MAP2K1 N122D unknown
MAP2K1 F53S unknown MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 S222D unknown
MAP2K1 P124Q unknown
BRAF V600E MAP2K1 P124Q
BRAF V600K MAP2K1 P124Q
MAP2K1 P264S unknown
MAP2K1 A347T unknown
MAP2K1 L177V unknown
MAP2K1 E120Q gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor
MAP2K1 I111S gain of function
MAP2K1 W247* unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E MAP2K1 C121S melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 C121S melanoma resistant Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 C121S melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Zelboraf (vemurafenib)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Clinical Study Actionable In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 C121S melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
MAP2K1 C121S Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 C121S Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 C121S Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 C121S Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 C121S colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture (PMID: 28179366). 28179366
MAP2K1 C121S colorectal cancer sensitive Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 C121S in culture (PMID: 28179366). 28179366
MAP2K1 C121S Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 C121S Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 C121S displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
ALK rearrange MAP2K1 K57N non-small cell lung carcinoma sensitive Ceritinib + Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of AZD6244, resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). 25394791
MAP2K1 K57N colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Vectibix (panitumumab) in culture (PMID: 26644315). 26644315
MAP2K1 K57N lymphatic system cancer sensitive Trametinib Clinical Study Actionable In a clinical study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 K57N mutation had a sustained clinical response to Mekinist (trametinib) for over 6 months (PMID: 26566875). 26566875
MAP2K1 K57N Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 K57N lung adenocarcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, selumetinib (AZD6244) inhibited phosphorylation of ERK in cells expressing MAP2K1 K57N and inhibited MAP2K1 K57N-dependent growth in cell culture (PMID: 18632602). 18632602
MAP2K1 K57N colorectal cancer sensitive Panitumumab + Trametinib Preclinical Actionable In a preclinical study, Vectibix (panitumumab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). 26644315
MAP2K1 K57N colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cell lines expressing MAP2K1 K57N were insensitive to Erbitux (cetuximab) in culture (PMID: 26644315). 26644315
MAP2K1 K57N Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 K57N colorectal cancer sensitive Cetuximab + Trametinib Preclinical Actionable In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57N in culture (PMID: 26644315). 26644315
MAP2K1 K57N Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 K57N Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 K57N Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 K57N Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 K57N displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
BRAF V600E MAP2K1 I111N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 I111N melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
MAP2K1 Q56P MAP2K1 H119Y MAP2K1 D351G EGFR G719S colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring MAP2K1 mutations Q56P, H119Y, and D351G and an EGFR G719S mutation demonstrated some sensitivity to Mekinist (trametinib) in culture, resulting in decreased cell viability (PMID: 26582713). 26582713
BRAF V600K MAP2K1 P124L melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive VX-11e Preclinical Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
MAP2K1 P124L melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, transformed human melanoma cells expressing MAP2K1 P124L demonstrated resistance to the MEK inhibitor, Selumetinib (AZD6244) (PMID: 19915144). 19915144
BRAF V600E MAP2K1 P124L melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 P124L melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 H119P melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E treated with Selumetinib (AZD6244) in culture demonstrated resistance, which was a result of the resistance mutation, MAP2K1 H119P (PMID: 19915144). 19915144
MAP2K1 K57E melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 (MEK1) K57E mutations restored extracellular signal-regulated kinase (ERK) activation in the presence of Tafinlar (dabrafenib) in cultured melanoma cell lines (PMID: 24463458). 24463458
BRAF V600E MAP2K1 K57E melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 K57E in a melanoma cell line harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600E MAP2K1 E203K melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 E203K melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 E203K melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma no benefit Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 L115P melanoma resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
MAP2K1 L115P Advanced Solid Tumor resistant CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) did not inhibit kinase activity of Map2k1 L115P expressed in transformed human kidney cells (PMID: 12370306). 12370306
MAP2K1 L115P melanoma resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) did not inhibit proliferation of melanoma cells expressing Map2k1 L115P (PMID: 19915144). 19915144
MAP2K1 L115P melanoma resistant CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) did not inhibit proliferation of melanoma cells expressing Map2k1 L115P (PMID: 19915144). 19915144
MAP2K1 Q56P BRAF V600E melanoma sensitive Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, combined treatment with selumetinib and PLX4720 strongly suppressed the emergence of resistant MAP2K1 mutations in BRAF V600E cells in culture (PMID: 19915144). 19915144
MAP2K1 Q56P BRAF V600E melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the MEK inhibitor selumetinib (AZD6244) cell culture. 19915144
MAP2K1 Q56P BRAF V600E melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the B-RAF inhibitor PLX4720 in culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 Q56P melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 Q56P melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). 28655712
MAP2K1 Q56P Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P lung adenocarcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Selumetinib (AZD6244), resulting in decreased cell viability (PMID: 26582713). 26582713
MAP2K1 Q56P lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). 26582713
MAP2K1 Q56P Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P lymphatic system cancer sensitive Cobimetinib Clinical Study Actionable In a clinical study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 Q56P mutation had a reduction of lymphatic infiltrates to background within a month of receiving Cotellic (cobimetinib) therapy (PMID: 26566875). 26566875
MAP2K1 Q56P Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P lung adenocarcinoma sensitive Refametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Refametinib (BAY86-9766), resulting in decreased cell viability (PMID: 26582713). 26582713
MAP2K1 Q56P Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P lung adenocarcinoma sensitive PD-0325901 Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to PD-0325901, resulting in decreased cell viability (PMID: 26582713). 26582713
MAP2K1 Q56P stomach cancer sensitive Selumetinib Preclinical Actionable In a preclinical study, selumetinib (AZD6244) inhibited growth of a gastric cancer cell line that requires MAP2K1 Q56P and inhibited phosphorylation of ERK in these cells (PMID: 22327936). 22327936
MAP2K1 Q56P Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 Q56P displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Q56P stomach cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a gastric cancer cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). 26582713
BRAF V600E MAP2K1 G128V melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P124S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and MAP2K1 P124S demonstrated decreased sensitivity to Selumetinib (AZD6244) compared to cells harboring BRAF V600E alone in culture (PMID: 22197931). 22197931
MAP2K1 V60E melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Tafinlar (dabrafenib) in culture (PMID: 24265153). 24265153
MAP2K1 V60E melanoma resistant Trametinib Preclinical Actionable In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Mekinist (trametinib) in culture (PMID: 24265153). 24265153
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R melanoma resistant Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF V600E MAP2K1 V60E melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 V60E melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
MAP2K1 K57T colorectal cancer sensitive Cetuximab + Trametinib Preclinical Actionable In a preclinical study, Erbitux (cetuximab) and Mekinist (trametinib) inhibited colorectal cancer cell lines expressing MAP2K1 K57T in culture (PMID: 26644315). 26644315
MAP2K1 K57T colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, a colorectal cancer cell line expressing MAP2K1 K57T was resistant to Vectibix (panitumumab) in culture (PMID: 26644315). 26644315
MAP2K1 K57T colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical case study, a patient with colorectal cancer developed liver metastases harboring MAP2K1 K57T that were insensitive to Erbitux (cetuximab) treatment and the mutation was confirmed to cause resistance in human colorectal cancer cell lines in culture (PMID: 26644315). 26644315
MAP2K1 K57T colorectal cancer sensitive Panitumumab + Trametinib Clinical Study Actionable In a clinical case study, a combination of Vectibix (panitumumab) and Mekinist (trametinib) caused tumor regression in a patient’s colorectal cancer metastases harboring MAP2K1 K57T after being identified pre-clinically as a combination likely to inhibit MAP2K1 K57T expressing colorectal cancer (PMID: 26644315). 26644315
BRAF V600E MAP2K1 I103N melanoma resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 I103N melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). 26267534
MAP2K1 I103N Advanced Solid Tumor decreased response CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) partially inhibited kinase activity of Map2k1 I103N expressed in transformed human kidney cells (PMID: 12370306). 12370306
MAP2K1 I103N melanoma resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) did not inhibit proliferation of melanoma cells expressing Map2k1 I103N (PMID: 19915144). 19915144
MAP2K1 I103N melanoma resistant CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) did not inhibit proliferation of melanoma cells expressing Map2k1 I103N (PMID: 19915144). 19915144
BRAF V600E MAP2K1 K59del melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E harboring MAP2K1 K59del in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma resistant Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
MAP2K1 L115A Advanced Solid Tumor decreased response CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) partially inhibited kinase activity of Map2k1 L115A expressed in transformed human kidney cells (PMID: 12370306). 12370306
MAP2K1 F129L Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F129L Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F129L Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F129L Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F129L Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F129L colorectal cancer sensitive RO4927350 Preclinical - Cell line xenograft Actionable In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F129L demonstrated sensitivity to treatment with RO4927350 in culture and in cell line xenograft models, demonstrating inhibition of tumor growth (PMID: 21705440). 21705440
MAP2K1 F129L Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F129L displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 Y134C KRAS Q61H lung adenocarcinoma no benefit Trametinib Preclinical Actionable In a preclinical study, treatment with Mekinist (trametinib) had no effect on a lung adenocarcinoma cell line co-harboring MAP2K1 Y134C and KRAS Q61H in culture (PMID: 26582713). 26582713
MAP2K1 Y134C KRAS Q61H lung adenocarcinoma no benefit Refametinib Preclinical Actionable In a preclinical study, treatment with Refametanib (BAY86-9766) had no effect on a lung adenocarcinoma cell line co-harboring MAP2K1 Y134C and KRAS Q61H in culture (PMID: 26582713). 26582713
MAP2K1 F53L Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 F53L conferred resistance to Erbitux (cetuximab) in colorectal cancer cells in culture (PMID: 28179366). 28179366
MAP2K1 F53L Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F53L demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in decreased cell viability (PMID: 26582713). 26582713
MAP2K1 F53L Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 F53L displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53L colorectal cancer sensitive Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring MAP2K1 F53L in culture (PMID: 28179366). 28179366
BRAF V600E MAP2K1 P162S melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P162S melanoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P162S melanoma sensitive Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by Selumetinib (AZD6244) in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (Ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D melanoma resistant CI-1040 Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by CI-1040 in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
MAP2K1 V211D Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 V211D displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 V211D Advanced Solid Tumor resistant Selumetinib Preclinical Actionable In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 V211D Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 V211D displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 V211D Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 V211D Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 V211D displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 V211D Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 V211D displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 F53S Advanced Solid Tumor sensitive CI-1040 Preclinical - Cell culture Actionable In a preclinical study, CI-1040 (PD184352) inhibited kinase activity of Map2k1 F53S expressed in transformed human kidney cells (PMID: 12370306). 12370306
BRAF V600E MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in cell culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma sensitive VX-11e Preclinical - Cell culture Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
MAP2K1 I111S Advanced Solid Tumor resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed resistance to Stivarga (regorafenib; BAY 73-4506), as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 I111S Advanced Solid Tumor sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed sensitivity to the Mek inhibitor, Selumetinib (AZD6244), as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 I111S Advanced Solid Tumor resistant PD98059 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed resistance to the Mek inhibitor, PD98059, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 I111S Advanced Solid Tumor resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed resistance to the Braf inhibitor, GDC-0879, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 I111S Advanced Solid Tumor resistant AZD8330 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed resistance to the Mek inhibitor, AZD8330, as demonstrated by constitutive activation of Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091
MAP2K1 I111S Advanced Solid Tumor sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Map2k1 I111S displayed sensitivity to the Braf inhibitor, PLX4720, as demonstrated by reversal of active Map2k1 in transformed human kidney cells (PMID: 29753091). 29753091