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MAP2K1 P124S - Gene Variant Detail

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Gene MAP2K1
Variant P124S
Impact List missense
Protein Effect unknown
Gene Variant Descriptions MAP2K1 P124S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124S results in increased Erk1/2 phosphorylation and confers resistance to Mek and Braf inhibitors (PMID: 19915144, PMID: 22197931) and an Egfr antibody (PMID: 33322618) in culture, but has similar induction of cell proliferation and viability levels to wild-type Map2k1 in culture (PMID: 29533785), and therefore, its effect on Map2k1 protein function is unknown.
Associated Drug Resistance Y
Category Variants Paths

MAP2K1 mutant MAP2K1 P124S

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Transcript NM_002755.4
gDNA chr15:g.66436824C>T
cDNA c.370C>T
Protein p.P124S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017022411 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38
NM_002755.3 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38
NM_002755 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38
NM_002755.4 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38
XM_017022411.2 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38
XM_017022411.3 chr15:g.66436824C>T c.370C>T p.P124S RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E MAP2K1 P124S melanoma sensitive VX-11e Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma decreased response Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived 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
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 resistant Trametinib Preclinical - Biochemical Actionable In a preclinical study, Mekinist (trametinib) inhibited Erk phosphorylation in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S in culture (PMID: 36442478). 36442478
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 resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S melanoma sensitive Cobimetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability in a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S, and resulted in an additive effect in a melanoma cell line harboring both BRAF V600E and MAP2K1 P124S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Braftovi (encorafenib) and Mektovi (binimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S colon adenocarcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S melanoma resistant Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S colon adenocarcinoma resistant Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S melanoma decreased response Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was less responsive to Ulixertinib (BVD-523) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478). 36442478
BRAF V600E MAP2K1 P124S melanoma decreased response Ravoxertinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was less responsive to Ravoxertinib (GDC-0994) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478). 36442478
BRAF V600K MAP2K1 P124S melanoma predicted - resistant Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in disease progression within 5 weeks in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124S (PMID: 24265153). 24265153