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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MAP2K2
mitogen-activated protein kinase kinase 2
Chromosome 19 Β· 19p13.3
NCBI Gene: 5605Ensembl: ENSG00000126934.16HGNC: HGNC:6842UniProt: B3KS97
272PubMed Papers
21Diseases
18Drugs
22Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolcell-cell junctionPDZ domain bindingprotein serine/threonine kinase activator activitycardiofaciocutaneous syndromemelanomaNoonan syndromecancer
✦AI Summary

MAP2K2 (MEK2) is a dual-specificity kinase that functions as a critical component of the MAPK signaling cascade by catalyzing the concomitant phosphorylation of threonine and tyrosine residues in ERK1 and ERK2 MAP kinases 1. The gene is located on chromosome 19 and plays essential roles in cell growth, differentiation, and survival signaling 1. MAP2K2 activates the ERK pathway, which is frequently dysregulated in cancer, making it an important therapeutic target 2. In colorectal cancer, the RAS/RAF/MEK/ERK pathway involving MAP2K2 can be suppressed by certain ribosomal proteins 3. Clinical studies demonstrate that MEK1/2 inhibitors targeting MAP2K2 show significant efficacy across various cancer types, including histiocytic neoplasms with an 89% overall response rate 4 and BRAF-mutated tumors with a 38% response rate 5. In multiple myeloma, MAP2K2 promotes cell proliferation through the YTHDF2/STAT5A/MAP2K2/p-ERK signaling axis 6. Additionally, MAP2K2 contributes to resistance against VEGFR inhibitors in renal cell carcinoma through a positive feedback loop with transcription factor SP1 2. These findings establish MAP2K2 as both a key oncogenic driver and a validated therapeutic target across multiple cancer types.

Sources cited
1
MAP2K2 encodes MEK2, located on chromosome 7q32, and phosphorylates ERK1/ERK2 in cell growth and differentiation pathways
PMID: 10828601
2
MAP2K2 drives VEGFR inhibitor resistance in renal cell carcinoma through SP1 positive feedback loop
PMID: 39781472
3
MAP2K2 is part of RAS/RAF/MEK/ERK pathway that can be suppressed by ribosomal proteins in colorectal cancer
PMID: 34026451
4
MEK1/2 inhibitors targeting MAP2K2 showed 89% response rate in histiocytic neoplasms clinical trial
PMID: 30867592
5
MEK1/2 inhibitor trametinib combined with BRAF inhibitor showed 38% response rate in BRAF-mutated tumors
PMID: 32758030
6
MAP2K2 promotes multiple myeloma cell proliferation via YTHDF2/STAT5A/MAP2K2/p-ERK signaling axis
PMID: 35075244
Disease Associationsβ“˜21
cardiofaciocutaneous syndromeOpen Targets
0.86Strong
melanomaOpen Targets
0.69Moderate
Noonan syndromeOpen Targets
0.64Moderate
cancerOpen Targets
0.62Moderate
rasopathyOpen Targets
0.57Moderate
neoplasmOpen Targets
0.56Moderate
neurofibromatosis type 1Open Targets
0.56Moderate
metastatic melanomaOpen Targets
0.55Moderate
Costello syndromeOpen Targets
0.51Moderate
hypertrophic cardiomyopathyOpen Targets
0.50Moderate
cutaneous melanomaOpen Targets
0.47Moderate
plexiform neurofibromaOpen Targets
0.45Moderate
cardiofaciocutaneous syndrome 1Open Targets
0.44Moderate
Abnormality of the cardiovascular systemOpen Targets
0.42Moderate
lung cancerOpen Targets
0.41Moderate
low grade gliomaOpen Targets
0.41Moderate
non-small cell lung carcinomaOpen Targets
0.40Moderate
neurodegenerative diseaseOpen Targets
0.39Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.39Weak
gliomaOpen Targets
0.38Weak
Cardiofaciocutaneous syndrome 4UniProt
Pathogenic Variants22
NM_030662.4(MAP2K2):c.170T>G (p.Phe57Cys)Pathogenic
Cardiofaciocutaneous syndrome 4|not provided|Cardio-facio-cutaneous syndrome|RASopathy
β˜…β˜…β˜…β˜†2024β†’ Residue 57
NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys)Likely pathogenic
RASopathy|Cardio-facio-cutaneous syndrome|not provided|Noonan syndrome;Cardio-facio-cutaneous syndrome|Noonan syndrome 1
β˜…β˜…β˜…β˜†2024β†’ Residue 134
NM_030662.4(MAP2K2):c.400T>C (p.Tyr134His)Pathogenic
Cardio-facio-cutaneous syndrome|Cardiofaciocutaneous syndrome 4|not provided|RASopathy|Noonan syndrome and Noonan-related syndrome|MAP2K2-related disorder|Noonan syndrome 1
β˜…β˜…β˜…β˜†2024β†’ Residue 134
NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)Pathogenic
Cardiofaciocutaneous syndrome 4|not provided|Cardio-facio-cutaneous syndrome|RASopathy
β˜…β˜…β˜…β˜†2024β†’ Residue 128
NM_030662.4(MAP2K2):c.619G>A (p.Glu207Lys)Likely pathogenic
RASopathy|not provided|Cardio-facio-cutaneous syndrome|Cardio-facio-cutaneous syndrome;Noonan syndrome
β˜…β˜…β˜…β˜†2017β†’ Residue 207
NM_030662.4(MAP2K2):c.169T>G (p.Phe57Val)Pathogenic
Cardiofaciocutaneous syndrome 4|Cardio-facio-cutaneous syndrome
β˜…β˜…β˜…β˜†2017β†’ Residue 57
NM_030662.4(MAP2K2):c.190G>T (p.Val64Phe)Likely pathogenic
not provided|RASopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 64
NM_030662.4(MAP2K2):c.169T>C (p.Phe57Leu)Pathogenic
not provided|RASopathy|Cardiofaciocutaneous syndrome 4
β˜…β˜…β˜†β˜†2025β†’ Residue 57
NM_030662.4(MAP2K2):c.383C>T (p.Pro128Leu)Pathogenic
Castleman-Kojima disease|MAP2K2-related disorder|Cardiofaciocutaneous syndrome 4|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 128
NM_030662.4(MAP2K2):c.395G>A (p.Gly132Asp)Pathogenic
Cardiofaciocutaneous syndrome 4|RASopathy|not provided|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2024β†’ Residue 132
NM_030662.4(MAP2K2):c.183A>C (p.Lys61Asn)Pathogenic
not provided|Cardiofaciocutaneous syndrome 4|RASopathy
β˜…β˜…β˜†β˜†2022β†’ Residue 61
NM_030662.4(MAP2K2):c.181A>G (p.Lys61Glu)Pathogenic
not provided|Cardiofaciocutaneous syndrome 1|RASopathy|Cardiofaciocutaneous syndrome 4
β˜…β˜…β˜†β˜†2022β†’ Residue 61
NM_030662.4(MAP2K2):c.376A>G (p.Asn126Asp)Pathogenic
Cardiofaciocutaneous syndrome 4|Cardio-facio-cutaneous syndrome|RASopathy
β˜…β˜…β˜†β˜†2021β†’ Residue 126
NM_030662.4(MAP2K2):c.395G>T (p.Gly132Val)Pathogenic
RASopathy
β˜…β˜†β˜†β˜†2025β†’ Residue 132
NM_030662.4(MAP2K2):c.334C>T (p.Arg112Trp)Likely pathogenic
RASopathy
β˜…β˜†β˜†β˜†2025β†’ Residue 112
NM_030662.4(MAP2K2):c.180G>C (p.Gln60His)Likely pathogenic
Cardiofaciocutaneous syndrome 4
β˜…β˜†β˜†β˜†2024β†’ Residue 60
NM_030662.4(MAP2K2):c.368A>C (p.His123Pro)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 123
NM_030662.4(MAP2K2):c.167C>A (p.Ala56Asp)Likely pathogenic
Cardiofaciocutaneous syndrome 4
β˜…β˜†β˜†β˜†2023β†’ Residue 56
NM_030662.4(MAP2K2):c.171T>A (p.Phe57Leu)Pathogenic
RASopathy
β˜…β˜†β˜†β˜†2018β†’ Residue 57
NM_030662.4(MAP2K2):c.210_212del (p.Asp71del)Pathogenic
Smith-Magenis Syndrome-like
β˜…β˜†β˜†β˜†2016β†’ Residue 71
View on ClinVar β†—
Drug Targets18
AS-703988Phase I
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
AVUTOMETINIBPhase III
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
ovarian cancer
AZD-8330Phase I
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
BINIMETINIBApproved
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
melanoma
CI-1040Phase II
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
lung cancer
COBIMETINIBApproved
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
melanoma
COBIMETINIB FUMARATEApproved
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
metastatic melanoma
MIRDAMETINIBApproved
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
plexiform neurofibroma
PIMASERTIBPhase II
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
colorectal cancer
REFAMETINIBPhase III
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
RG-7167Phase I
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor
RO-4987655Phase I
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
SELUMETINIBApproved
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
neurofibromatosis type 1
SELUMETINIB SULFATEApproved
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor
neurofibromatosis
TAK-733Phase II
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
TRAMETINIBApproved
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
metastatic melanoma
TRAMETINIB DIMETHYL SULFOXIDEApproved
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
lung cancer
WX-554Phase I/II
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
Related Genes
BRAFProtein interaction100%MAPK14Protein interaction100%HRASProtein interaction100%KRASProtein interaction100%MAP3K1Protein interaction100%NRASProtein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
79%
Lung
78%
Brain
66%
Bone Marrow
63%
Heart
53%
Gene Interaction Network
Click a node to explore
MAP2K2BRAFMAPK14HRASKRASMAP3K1NRAS
PROTEIN STRUCTURE
Preparing viewer…
PDB4H3Q Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.61 [0.45–0.86]
RankingsWhere MAP2K2 stands among ~20K protein-coding genes
  • #1,352of 20,598
    Most Researched272 Β· top 10%
  • #190of 1,025
    FDA-Approved Drug Targets8 Β· top quartile
  • #2,090of 5,498
    Most Pathogenic Variants22
  • #7,499of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedMAP2K2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Dual Inhibition of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells.
PMID: 34026451
Adv Sci (Weinh) Β· 2021
1.00
2
Efficacy of MEK inhibition in patients with histiocytic neoplasms.
PMID: 30867592
Nature Β· 2019
0.90
3
Dabrafenib and Trametinib in Patients With Tumors With
PMID: 32758030
J Clin Oncol Β· 2020
0.80
4
Selumetinib: First Approval.
PMID: 32504375
Drugs Β· 2020
0.70
5
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
PMID: 22197931
Nat Genet Β· 2011
0.68