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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

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Transcript NM_002755.3
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_002755.3 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

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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 Cobimetinib Preclinical 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 predicted - resistant Binimetinib Preclinical 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 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 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 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 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 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
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 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 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 Koselugo (selumetinib) 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 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 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 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 Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
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
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 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 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 K601E MAP2K1 V211D colon cancer sensitive MAP855 Preclinical - Pdx Actionable In a preclinical study, MAP955 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer resistant Binimetinib + Cetuximab Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer predicted - resistant Binimetinib + Panitumumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer resistant Binimetinib Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MAP2K1 mutant Erdheim-Chester disease sensitive Cobimetinib Guideline Actionable Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). detail...
MAP2K1 mutant Erdheim-Chester disease sensitive Trametinib Guideline Actionable Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN Guidelines). detail...
Molecular Profile Protein Effect Treatment Approaches
MAP2K1 V211D gain of function
BRAF V600E MAP2K1 V211D
BRAF K601E MAP2K1 V211D