Gene: MAP2K1

Alternate names for this Gene: CFC3|MAPKK1|MEK1|MEL|MKK1|PRKMK1

Gene Summary: The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development.

Gene is located in Chromosome: 15

Location in Chromosome : 15q22.31

Description of this Gene: mitogen-activated protein kinase kinase 1

Type of Gene: protein-coding

rs1057519728 in MAP2K1 gene and Adenocarcinoma of lung (disorder) PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

rs1057519909 in MAP2K1 gene and Adenocarcinoma of prostate PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs727504317 in MAP2K1 gene and Autism Spectrum Disorders PMID 30763456 2019 Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations.

rs11629783 in MAP2K1 gene and Body mass index PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

rs121908594 in MAP2K1 gene and CARDIOFACIOCUTANEOUS SYNDROME 3 PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17704260 2007 Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

PMID 25423878 2015 A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines.

rs121908594 in MAP2K1 gene and Cardio-facio-cutaneous syndrome PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

PMID 24236184 2013 Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel.

PMID 22848035 2012 Case report: Noonan syndrome with multiple giant cell lesions and review of the literature.

PMID 24637312 2014 Cardio-facio-cutaneous syndrome with precocious puberty, growth hormone deficiency and hyperprolactinemia.

PMID 23093928 2012 A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.

PMID 17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.

PMID 17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

PMID 18413255 2008 Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome.

PMID 17551924 2007 Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17567882 2007 The patient died shortly thereafter and his post-mortem DNA analysis revealed a MEK1 mutation (Y130C) previously reported in CFC.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

PMID 18632602 2008 Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma.

PMID 20354455 2010 MEK1 and AKT2 mutations in Japanese lung cancer.

PMID 19915144 2009 MEK1 mutations confer resistance to MEK and B-RAF inhibition.

PMID 23569304 2013 Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma.

PMID 24803665 2014 Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations.

PMID 28049852 2017 In vivo severity ranking of Ras pathway mutations associated with developmental disorders.

PMID 29493581 2018 ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.

PMID 22327936 2012 Oncogenic MAP2K1 mutations in human epithelial tumors.

PMID 18060073 2007 Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.

PMID 19411838 2009 MEK1 mutations, but not ERK2 mutations, occur in melanomas and colon carcinomas, but none in thyroid carcinomas.

PMID 25049390 2014 Next-generation sequencing identifies rare variants associated with Noonan syndrome.

PMID 17704260 2007 Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

rs121908596 in MAP2K1 gene and Coarse features PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

rs1057519728 in MAP2K1 gene and Colorectal Neoplasms PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121908595 in MAP2K1 gene and Congenital anomaly of face PMID 17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.

PMID 17567882 2007 Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.

PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

PMID 17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17551924 2007 Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

rs121908595 in MAP2K1 gene and Constipation PMID 17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

PMID 17567882 2007 Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17551924 2007 Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

PMID 17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.

PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

rs1057519728 in MAP2K1 gene and Cutaneous Melanoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121908595 in MAP2K1 gene and Dysmorphic features PMID 16474404 2006 Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.

PMID 25423878 2015 A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines.

PMID 24101678 2014 Autism traits in the RASopathies.

PMID 22753777 2012 MEK genomics in development and disease.

PMID 22589294 2012 Prevalence of sequence variants in the RAS-mitogen activated protein kinase signaling pathway in pre-adolescent children with hypertrophic cardiomyopathy.

PMID 27862862 2017 Variability in clinical and neuropsychological features of individuals with MAP2K1 mutations.

PMID 12529707 2003 PTPN11 mutations are not responsible for the Cardiofaciocutaneous (CFC) syndrome.

PMID 12239713 2002 CFC index for the diagnosis of cardiofaciocutaneous syndrome.

PMID 17704260 2007 Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

PMID 20958325 2010 Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

PMID 21654472 2011 Orthopaedic conditions in Ras/MAPK related disorders.

rs1057519728 in MAP2K1 gene and Gastric Adenocarcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121908595 in MAP2K1 gene and Kyphosis deformity of spine PMID 17567882 2007 Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.

PMID 17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.

PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17551924 2007 Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

PMID 17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

rs121908596 in MAP2K1 gene and Left Ventricular Hypertrophy PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

rs1057519909 in MAP2K1 gene and Lymphoma, Non-Hodgkin, Familial PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121908596 in MAP2K1 gene and Macroglossia PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

rs1057519732 in MAP2K1 gene and Malignant Uterine Corpus Neoplasm PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519730 in MAP2K1 gene and Neoplasms PMID 19915144 2009 MEK1 mutations confer resistance to MEK and B-RAF inhibition.

PMID 23614898 2013 Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.

rs1057519729 in MAP2K1 gene and Non-Small Cell Lung Carcinoma PMID 7651428 1995 RAS signalling is abnormal in a c-raf1 MEK1 double mutant.

PMID 18632602 2008 We also screened 85 NSCLC cell lines for MEK1 exon 2 mutations; one line (NCI-H1437) harbors a Q56P substitution, a known transformation-competent allele of MEK1 originally identified in rat fibroblasts, and is sensitive to treatment with AZD6244.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 18060073 2007 Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.

PMID 18632602 2008 Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma.

rs727504317 in MAP2K1 gene and Noonan Syndrome PMID 22327936 2012 Oncogenic MAP2K1 mutations in human epithelial tumors.

PMID 17704260 2007 Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

PMID 18060073 2007 Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.

PMID 19411838 2009 MEK1 mutations, but not ERK2 mutations, occur in melanomas and colon carcinomas, but none in thyroid carcinomas.

rs112293876 in MAP2K1 gene and Prostate carcinoma PMID 29892016 2018 Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

rs121908596 in MAP2K1 gene and Pulmonary Stenosis PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

rs11637556 in MAP2K1 gene and Renal Cell Carcinoma PMID 28598434 2017 Genome-wide association study identifies multiple risk loci for renal cell carcinoma.

rs1057519909 in MAP2K1 gene and Squamous cell carcinoma of the head and neck PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs121908595 in MAP2K1 gene and Strabismus PMID 17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.

PMID 16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

PMID 18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

PMID 17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

PMID 17567882 2007 Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome.

PMID 17551924 2007 Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome.

PMID 19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.

rs1057519732 in MAP2K1 gene and Transitional cell carcinoma of bladder PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs2053005 in MAP2K1 gene and mathematical ability PMID 30038396 2018 Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.

rs1057519728 in MAP2K1 gene and melanoma PMID 22197931 2011 Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.

PMID 23569304 2013 Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma.

PMID 19915144 2009 MEK1 mutations confer resistance to MEK and B-RAF inhibition.

PMID 22588879 2012 Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors.

PMID 21383288 2011 Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.

PMID 24448821 2014 We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201.

PMID 22622578 2012 Melanoma genome sequencing reveals frequent PREX2 mutations.

PMID 23614898 2013 Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.

PMID 21107320 2010 COT drives resistance to RAF inhibition through MAP kinase pathway reactivation.

PMID 19915144 2009 One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 23444215 2013 Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma.