Gene

MAP2K1

mitogen-activated protein kinase kinase 1

Explore in graph →CI-GENE-00011949HGNC:6840 ENSG00000169032 NCBI 5604 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (32)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–32 of 32 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
BRAF Mutation + FGFR2 Fusion + MAP2K1 MutationBRAF FGFR2 MAP2K11
(diagnostic)	Multinodular and Vacuolated Neuronal TumorALIAS

Cohorts

Alteration frequency by cohort (48)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved48 cohort rows · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Histiocytosis Cobimetinib (MSK, Nature 2019) histiocytosis_cobi_msk_2019	Histiocytic and Dendritic Cell Neoplasm	Ssm

Literature

Linked publications (6)

25 per page, newest first.

pubmedPublishedShowing 1–6 of 6 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

MAP2K1 (MEK1) Mutations Define a Distinct Subset of Lung Adenocarcinoma Associated with Smoking.
· Clin Cancer Res · 2015 · PMID 25351745 · validated civic_curation pubmed
Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.
· J Clin Oncol · 2011 · PMID 21383288 · validated civic_curation pubmed
Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer.
· J Clin Oncol · 2015 · PMID 26324360 · validated civic_curation pubmed
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
· Nat Genet · 2011 · PMID 22197931 · validated civic_curation

MAP2K1 K57N3
(prognostic)	Lung Adenocarcinoma	Prognostic	B	Supports Poor Outcome	3	accepted	EID2935 In a study of 6,024 lung adenocarcinomas, 36 conferred MEK1 mutations whereby 64% (n=23) were K57N and 19% (n=7) were Q56P. Median overall survival of MEK1-mutated tumors was not significantly differe… (full text at CIViC) PMID 25351745 · Arcila et al., 2015 · Open in CIViC	civic
Selumetinib	Melanoma	Predictive	C	Supports Resistance	3	submitted	EID7709 In a phase 2 clinical trial, patients with BRAF V600-mutated melanoma were treated with selumetinib. One patient whose tumor did not response had a MAP2K1 K57N mutation. PMID 23444215 · Catalanotti et al., 2013 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	D	Supports Sensitivity Response	2	accepted	EID2936 Mutational profiling of 207 lung adenocarcinomas identified in 2 of with activating mutation in exon 2 of MEK1 (K57N) in the nonkinase portion of the kinase. Neither of these two tumors harbored known… (full text at CIViC) PMID 18632602 · Marks et al., 2008 · Open in CIViC	civic

MAP2K1 P124S3
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	4	accepted	EID12986 MAP2K1 P124S was shown to constitutively activate ERK1/2 phosphorylation in the absence of serum in transiently transfected HEK293T cells (Fig 4a). In an NIH3T3 transformation assay (performed in trip… (full text at CIViC) PMID 22197931 · Nikolaev et al., 2011 · Open in CIViC	civic
Selumetinib	Melanoma	Predictive	D	Supports Resistance	3	accepted	EID12 A375 cells expressing MAP2K1 P124S mutation conferred an approximately 5-fold increased resistance to selumetinib (AZD6244) induced growth inhibition when compared to untransduced cells, cells express… (full text at CIViC) PMID 19915144 · Emery et al., 2009 · Open in CIViC	civic
Dabrafenib + VemurafenibSubstitutes	Melanoma	Predictive	C	Supports Resistance	4	submitted	EID7660 In a retrospective study, resistance mechanisms to BRAF inhibitor such as vemurafenib or dabrafenib in patients with BRAF V600 mutated melanoma were evaluated Five MAP2K1 gene mutations (encodes the M… (full text at CIViC) PMID 24265153 · Van Allen et al., 2014 · Open in CIViC	civic

MAP2K1 Q56P3
(diagnostic)	Multinodular and Vacuolated Neuronal TumorALIAS	Diagnostic	C	Supports Positive	2	submitted	EID12461 NGS targeting 479 cancer-associated genes were performed on two MVNT cases: a 63-year-old female with left-hand paresthesia and a 54-year-old male with long-standing epilepsy, both located in the righ… (full text at CIViC) PMID 29428973 · Pekmezci et al., 2018 · Open in CIViC	civic
Selumetinib	Melanoma	Predictive	D	Supports Resistance	3	accepted	EID13 A375 cells expressing MAP2K1 Q56P mutation conferred an approximately 100-fold increased resistance to selumetinib (AZD6244) induced growth inhibition when compared to untransduced cells, cells expres… (full text at CIViC) PMID 19915144 · Emery et al., 2009 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	C	Supports Resistance	—	submitted	EID4727 In a retrospective study of a phase 2 clinical trial (NCT00949702), of 132 BRAF mutation positive metastatic melanoma patients treated with vemurafenib monotherapy, the MAP2K1 Q56P mutation was associ… (full text at CIViC) PMID 23569304 · Trunzer et al., 2013 · Open in CIViC	civic

MAP2K1 V211D2
Binimetinib + PanitumumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	submitted	EID7580 Patients with metastatic colorectal cancer harboring BRAF V601E mutation were treated with binimetinib and panitumumab combination. Gene profiling at progressed tumor revealed MEK1 V211D mutation. V21… (full text at CIViC) PMID 31227518 · Gao et al., 2019 · Open in CIViC	civic
MAP855	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID7581 Patients with metastatic colorectal cancer harboring BRAF V601E mutation were treated with binimetinib and panitumumab combination. Gene profiling at progressed tumor revealed MEK1 V211D mutation. V21… (full text at CIViC) PMID 31227518 · Gao et al., 2019 · Open in CIViC	civic

KRAS Mutation + MAP2K1 Mutation + MAP2K2 Mutation + NRAS Mutation + RAF1 MutationRAF1 MAP2K1 MAP2K2 KRAS NRAS2
Cobimetinib	Erdheim-Chester Disease	Predictive	B	Supports Sensitivity Response	4	submitted	EID11328 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic
〃	Langerhans Cell Histiocytosis	Predictive	B	Supports Sensitivity Response	4	submitted	EID11329 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic