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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, PMID: 32361034), histiocytic sarcoma (PMID: 29768143), and Map2k1 mutations are often associated with resistance to Mek and Raf inhibition (PMID: 29753091).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
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.
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, Feb 2020).
A158T missense unknown MAP2K1 A158T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). A158T has been identified in the scientific literature (PMID: 25256751), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Mar 2020).
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, Feb 2020).
A390T missense unknown MAP2K1 A390T does not lie within any known functional domains of the Map2k1 protein (UniProt.org). A390T has been identified in sequencing studies (PMID: 29340109), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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.
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, Feb 2020).
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.
amp none no effect MAP2K1 amp indicates an increased number of copies of the MAP2K1 gene. However, the mechanism causing the increase is unspecified.
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, Feb 2020).
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
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, Feb 2020).
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, Feb 2020).
D336H missense unknown MAP2K1 D336H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D336H has been identified in sequencing studies (PMID: 22923433), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Mar 2020).
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, Feb 2020).
D351N missense unknown MAP2K1 D351N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). D351N has been identified in sequencing studies (PMID: 25363767), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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).
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).
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).
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).
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).
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). Y
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).
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, Feb 2020).
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, Feb 2020).
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).
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).
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
F53C missense gain of function - predicted MAP2K1 F53C does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53C results in increased Erk1/2 phosphorylation in vitro and has been associated with resistance to BRAF inhibitors (PMID: 30341394), and therefore, is predicted to result in a gain of Map2k1 protein function. Y
F53I missense unknown MAP2K1 F53I does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53I has been identified in sequencing studies (PMID: 28179366), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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
F53S missense gain of function MAP2K1 F53S does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53S demonstrates phosphorylation profile similar to wild-type Map2k1 (PMID: 29753091), and results in increased Erk phosphorylation in cell culture (PMID: 16439621, PMID: 12370306).
F53V missense unknown MAP2K1 F53V does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53V has been identified in the scientific literature (PMID: 27511764, PMID: 28664935), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
F53Y missense gain of function - predicted MAP2K1 F53Y does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53Y results in increased Erk phosphorylation in culture (PMID: 30776432), and therefore, is predicted to lead to a gain of Map2k1 protein function.
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: 26566875, PMID: 29483135).
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, Mar 2020).
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, Mar 2020).
G128C missense unknown MAP2K1 G128C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G128C has been identified in sequencing studies (PMID: 30933438, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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).
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.
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, Feb 2020).
G128V missense unknown 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), but has shown increased Erk phosphorylation, enhanced cell cycle progression, increased colony formation, and elevated autophagy induction compared to wild-type Map2k1 in culture (PMID: 31972311), and therefore, its effect on Map2k1 protein function is unknown. Y
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, Feb 2020).
G294R missense unknown MAP2K1 G294R lies within the protein kinase domain of the Map2k1 protein (UniProt.org). G294R has been identified in sequencing studies (PMID: 30239046), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
G301* nonsense unknown MAP2K1 G301* results in a premature truncation of the Map2k1 protein at amino acid 301 of 393 (UniProt.org). G301* has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Mar 2020).
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, Feb 2020).
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, Feb 2020).
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, Feb 2020). Y
H119Q missense unknown MAP2K1 H119Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). H119Q has been identified in sequencing studies (PMID: 24185513), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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, Feb 2020).
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
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).
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
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
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
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
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
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).
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, Feb 2020).
I99G missense gain of function - predicted MAP2K1 I99G lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I99G results in increased Erk2 phosphorylation and confers resistance to some Mek and Braf inhibitors in culture (PMID: 31925410), and therefore, is predicted to result in a gain of Map2k1 protein function. Y
I99M missense unknown MAP2K1 I99M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I99M has been identified in the scientific literature (PMID: 31925410), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, May 2020).
I99T missense gain of function - predicted MAP2K1 I99T lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I99T results in increased Erk2 phosphorylation and confers resistance to some Mek and Braf inhibitors in culture (PMID: 31925410), and therefore, is predicted to result in a gain of Map2k1 protein function. 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).
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.
inact mut unknown loss of function MAP2K1 inact mut indicates that this variant results in a loss of function of the Map2k1 protein. However, the specific amino acid change has not been identified.
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, Feb 2020).
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, Feb 2020).
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).
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
K57M missense gain of function MAP2K1 K57M does not lie within any known functional domains of the Map2k1 protein (UniProt.org). K57M results in increased Erk phosphorylation, enhanced cell cycle progression, increased colony formation, and induction of autophagy in cultured cells (PMID: 31972311).
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
K57T missense gain of function - predicted MAP2K1 K57T lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). K57T results in increased Erk1/2 phosphorylation in culture (PMID: 30341394), and has been demonstrated to occur as a secondary drug resistance mutation (PMID: 26644315, PMID: 28819429, PMID: 30341394), and therefore, is predicted to result in a gain of Map2k1 protein function. Y
K59del deletion unknown MAP2K1 K59del results in the deletion of an amino acid in the protein kinase domain of the Map2k1 protein at amino acid 59 (UniProt.org). K59del results in increased Mek and Erk phosphorylation in culture (PMID: 22389471), but demonstrates autophosphorylation levels similar to wild-type Map2k1 in another study (PMID: 29753091), and therefore, its effect on Map2k1 protein function is unknown.
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).
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).
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
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, Feb 2020). Y
L177M missense gain of function - predicted MAP2K1 L177M lies within the protein kinase domain of the Map2k1 protein (UniProt.org). L177M demonstrates a moderate increase in basal Erk signaling, but remains sensitive to Raf pathway activation (PMID: 29483135), and therefore, is predicted to result in a gain of Map2k1 protein function.
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, Feb 2020).
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, Feb 2020).
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).
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).
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).
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
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, Feb 2020).
mutant unknown unknown MAP2K1 mutant indicates an unspecified mutation in the MAP2K1 gene.
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, Feb 2020).
N382H missense unknown MAP2K1 N382H does not lie within any known functional domains of the Map2k1 protein (UniProt.org). N382H does not lead to Erk phosphorylation in culture (PMID: 22197931), however, has not been fully biochemically characterized and therefore, its effect on Map2k1 protein function is unknown.
P105_I107del deletion unknown MAP2K1 P105_I107del results in the deletion of three amino acids in the protein kinase domain of the Map2k1 protein from amino acids 105 to 107 (UniProt.org). P105_I107del has been identified in the scientific literature (PMID: 30867592), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Oct 2019).
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
P124Q missense unknown MAP2K1 P124Q lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124Q results in increased Erk1/2 phosphorylation in culture, and is associated with resistance to a Raf inhibitor (PMID: 25370473), but demonstrates autophosphorylation and kinase activity similar to wild-type Map2k1 in another study (PMID: 29753091), and therefore, its effect on Map2k1 protein function is unknown. Y
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 it 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 confers resistance to Mek and Braf inhibitors in melanoma cells (PMID: 19915144, PMID: 22197931). Y
P162S missense unknown MAP2K1 P162S lies within the protein kinase domain of the Map2k1 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, Feb 2020).
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, PMID: 27261508), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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, Feb 2020).
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).
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, Feb 2020).
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).
Q354H missense unknown MAP2K1 Q354H lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Q354H has been identified in sequencing studies (PMID: 30111351), but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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
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).
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).
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, Feb 2020).
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, Feb 2020).
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, Feb 2020).
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, Feb 2020).
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).
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, Feb 2020).
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).
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, Feb 2020).
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 biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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).
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).
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.
S222D missense unknown MAP2K1 S222D lies within the protein kinase domain of the Map2k1 protein (UniProt.org). S222D results in constitutive activation of Map2k1 when combined with MAP2K1 S218D or MAP2K1 S226D in culture (PMID: 7936666, PMID: 12506122), but has not been individually characterized and therefore, its effect on Map2k1 protein function is unknown.
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, Feb 2020).
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, Feb 2020).
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, Feb 2020).
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).
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.
V211A missense unknown MAP2K1 V211A lies within the protein kinase domain of the Map2k1 protein (UniProt.org). V211A has not been characterized in the scientific literature and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).
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 to Map2k1, as demonstrated by increased phosphorylation of Mek and Erk in cultured cells and in vitro kinase assays, and also demonstrates Braf and Mek inhibitor resistance (PMID: 29753091, PMID: 19915144, PMID: 31227518). Y
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, Feb 2020)
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, Feb 2020).
V60E missense gain of function MAP2K1 V60E does not lie within any known functional domains of the Map2k1 protein (UniProt.org). V60E results in increased Erk signaling in cultured cells and tumor formation in orthotopic mouse models (PMID: 28263969), and has been described as a drug resistance mutation (PMID: 24265153, PMID: 28263969). Y
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).
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, Feb 2020).
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, Feb 2020).
wild-type none no effect Wild-type MAP2K1 indicates that no mutation has been detected within the MAP2K1 gene.
Y130C missense unknown MAP2K1 Y130C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y130C demonstrates a phosphorylation profile similar to wild-type Map2k1 (PMID: 29753091), but in another study results in increased Erk phosphorylation in cell culture (PMID: 16439621, PMID: 18060073, PMID: 17981815, PMID: 31972311), and elevated cell cycle progression and colony formation compared to wild-type Map2k1 (PMID: 31972311), and therefore, its effect on Map2k1 protein function is unknown.
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.
Y130N missense no effect - predicted MAP2K1 Y130N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y130N has been demonstrated to result in 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.
Y134C missense unknown MAP2K1 Y134C lies within the protein kinase domain of the Map2k1 protein (UniProt.org). Y134C has been identified in the scientific literature (PMID: 18186519) but has not been biochemically characterized and therefore, its effect on Map2k1 protein function is unknown (PubMed, Feb 2020).