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Gene | MAP2K1 |
Variant | V211D |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | 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). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 V211D |
Transcript | NM_002755.4 |
gDNA | chr15:g.66481818T>A |
cDNA | c.632T>A |
Protein | p.V211D |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755.4 | chr15:g.66481818T>A | c.632T>A | p.V211D | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66481818T>A | c.632T>A | p.V211D | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66481818T>A | c.632T>A | p.V211D | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | predicted - resistant | Binimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 |
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 | predicted - resistant | Cobimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Cotellic (cobimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 |
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 | 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 | 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 |