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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 | 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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E MAP2K1 V211D | melanoma | resistant | CI-1040 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 V211D | melanoma | resistant | Selumetinib | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
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 | 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 | 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 | 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 | 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 | 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 | 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, Ulixertinib (BVD-523) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 |
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 | sensitive | MAP855 | Preclinical - Pdx | Actionable | In a preclinical study, MAP855 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 | 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 |
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 |