MAP2K1 (MEK1) Gene: Function, Mutations, and Clinical Significance
Comprehensive biomedical overview of the MAP2K1 gene encoding MEK1, a key kinase in the RAS-RAF-MEK-ERK signaling pathway, including its role in cancer, cardiofaciocutaneous syndrome, and targeted therapy.
Gene Information Card
| Symbol | MAP2K1 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q22.31 |
| NCBI Gene ID | 5604 ncbi.nlm.nih.gov/gene/5604 |
| Ensembl ID | ENSG00000169032 |
| UniProt ID | Q02750 |
| OMIM ID | 176872 |
| HGNC ID | 6840 |
| Aliases | MEK1, MKK1, MAPKK1, PRKMK1 |
Description
The MAP2K1 gene encodes mitogen-activated protein kinase kinase 1 (MEK1), a dual-specificity kinase that phosphorylates and activates ERK1/2 (MAPK3/MAPK1). MEK1 is a central component of the RAS-RAF-MEK-ERK signaling cascade, which regulates cell proliferation, differentiation, and survival. Gain-of-function mutations in MAP2K1 are oncogenic drivers in various cancers, while germline mutations cause cardiofaciocutaneous syndrome. MEK1 is a validated therapeutic target; several MEK inhibitors (e.g., trametinib, cobimetinib) are approved for cancer treatment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiofaciocutaneous syndrome (CFC) | Germline gain-of-function mutations in MAP2K1 lead to constitutive activation of the RAS-MAPK pathway, causing developmental abnormalities including heart defects, distinctive facial features, and ectodermal anomalies. | ClinVar, OMIM #615278 |
| Non-small cell lung cancer | Somatic activating mutations (e.g., K57N, Q56P) in MAP2K1 drive ERK signaling and tumor growth; these mutations can confer resistance to EGFR inhibitors. | COSMIC, ClinVar |
| Melanoma | MAP2K1 mutations (e.g., P124S, E203K) are found in ~8% of melanomas and are associated with resistance to BRAF inhibitors. | COSMIC, ClinVar |
| Colorectal cancer | Recurrent MAP2K1 mutations (e.g., K57N) activate MEK-ERK signaling and may predict sensitivity to MEK inhibitors. | COSMIC, ClinVar |
| Langerhans cell histiocytosis | Activating MAP2K1 mutations (e.g., E102_I103del) are present in ~50% of cases, driving ERK pathway activation. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.2 | Medium |
| Heart | 12.5 | Medium |
| Lung | 15.8 | Medium |
| Liver | 10.3 | Low |
| Kidney | 14.1 | Medium |
| Testis | 20.6 | High |
| Ovary | 16.4 | Medium |
| Skin | 13.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 22.3 | High expression |
| MCF7 (breast cancer) | 18.7 | Medium expression |
| HEK293 (embryonic kidney) | 25.1 | High expression |
| HeLa (cervical cancer) | 19.5 | Medium expression |
| SK-MEL-28 (melanoma) | 21.0 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| K57N | Missense | ~2% in melanoma, ~1% in NSCLC | Gain-of-function; increases MEK1 kinase activity and ERK phosphorylation |
| Q56P | Missense | Rare in multiple cancers | Gain-of-function; constitutive activation of MEK-ERK pathway |
| P124S | Missense | ~1% in melanoma | Gain-of-function; associated with BRAF inhibitor resistance |
| E203K | Missense | ~0.5% in melanoma | Gain-of-function; enhances MEK1 activity |
| E102_I103del | In-frame deletion | ~50% in Langerhans cell histiocytosis | Gain-of-function; deletion in negative regulatory region leading to constitutive activation |
Mutation functional classification
Loss of Function (LOF)
Rare; loss-of-function mutations in MAP2K1 are not well characterized and are not associated with known diseases. Most reported mutations are gain-of-function.
Gain of Function (GOF)
Common; activating mutations (e.g., K57N, Q56P, P124S) increase MEK1 kinase activity, leading to sustained ERK signaling and oncogenic transformation. These mutations are found in multiple cancer types and in cardiofaciocutaneous syndrome.
Dominant Negative (DN)
Not reported; no dominant-negative mutations have been described for MAP2K1 in the literature or curated databases.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAS-RAF-MEK-ERK signaling pathway (KEGG hsa04010)
• MAPK signaling pathway (KEGG hsa04010)
• EGFR tyrosine kinase inhibitor resistance (KEGG hsa01521)
• Signaling by Receptor Tyrosine Kinases (Reactome R-HSA-9006934)
• RAF/MAP kinase cascade (Reactome R-HSA-5673001)
Protein Summary
MEK1 (UniProt Q02750) is a 393-amino acid dual-specificity protein kinase that phosphorylates ERK1/2 at Thr-Glu-Tyr motifs. It contains an N-terminal negative regulatory region, a protein kinase domain, and a C-terminal tail. MEK1 is activated by RAF-mediated phosphorylation at Ser218 and Ser222. The protein is ubiquitously expressed and localizes to the cytoplasm and nucleus. MEK1 is a key node in the RAS-RAF-MEK-ERK cascade and is targeted by several FDA-approved inhibitors (trametinib, cobimetinib, binimetinib, selumetinib) for cancer therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP2K1 Knockout HEK293 Cell Line | EDJ-KQ17832 | Human | 5604 | Details Get a Quote |
| MAP2K1 Knockout A-549 Cell Line | EDJ-KQ20479 | Human | 5604 | Details Get a Quote |
| MAP2K1 Knockout HCT 116 Cell Line | EDJ-KQ20480 | Human | 5604 | Details Get a Quote |
| MAP2K1 Knockout HeLa Cell Line | EDJ-KQ20481 | Human | 5604 | Details Get a Quote |
| MAP2K1 (p.P124S) Point Mutation in HCT 116 Cell Line | EDC03119 | Human | 5604 | Details Get a Quote |
| MAP2K1 (p.E203K) Point Mutation in HCT 116 Cell Line | EDC03121 | Human | 5604 | Details Get a Quote |
| MAP2K1 (p.Q56P) Point Mutation in HAP1 Cell Line | EDC03533 | Human | 5604 | Details Get a Quote |
| MAP2K1 (p.H119Y) Point Mutation in HAP1 Cell Line | EDC03534 | Human | 5604 | Details Get a Quote |
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