MAP2K1

Chr 15

mitogen-activated protein kinase kinase 1

Also known as: CFC3, MAPKK1, MEK1, MEL, MKK1, PRKMK1

NCBI Gene: 5604ENSG00000169032UniProt: Q02750

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. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCardiofaciocutaneous syndrome 3
UniProtMelorheostosis, isolated

Clinical highlights

Gene-disease validity (ClinGen)
Noonan syndrome · ADLimitednot for standalone diagnostic reporting4 gene-disease associations curated in total
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
9
Active trials
192
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.38
LOEUF
GOF*
Mechanism· G2P
📖
GeneReview available — MAP2K1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?
0.38LOEUF
pLI 0.897
Z-score 3.59
OE 0.15 (0.07–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.11Z-score
OE missense 0.41 (0.34–0.48)
88 obs / 216.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.15 (0.07–0.38)
0≤0.351.4
Missense OE?0.41 (0.34–0.48)
0≤0.61.4
Synonymous OE?1.09
0≤1.21.6
LoF obs/exp: 3 / 20.6Missense obs/exp: 88 / 216.8Syn Z: -0.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MAP2K1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

VCEP specificationsRASopathyReleased
Specifications ↗Panel ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Non Small Cell Lung CancerEGFR Gene MutationALK Gene Mutation

Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation

RECRUITING
NCT04322890Phase PHASE2Hunan Province Tumor HospitalStarted 2020-04-16
OsimertinibAlectinib 150 MGCrizotinib 250 MG
EGFR NP_005219.2:p.S492RKRAS Gene MutationMAP2K1 Gene Mutation

Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer

ACTIVE NOT RECRUITING
NCT03087071Phase PHASE2M.D. Anderson Cancer CenterStarted 2017-12-29
Laboratory Biomarker AnalysisPanitumumabTrametinib
Hormone-Resistant Prostate CancerMetastatic Prostate CarcinomaRecurrent Prostate Carcinoma

Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer

ACTIVE NOT RECRUITING
NCT02881242Phase PHASE2Jonsson Comprehensive Cancer CenterStarted 2018-01-30
Laboratory Biomarker AnalysisQuality-of-Life AssessmentTrametinib
Hairy Cell Leukemia

Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL

ACTIVE NOT RECRUITING
NCT04324112Phase PHASE2National Cancer Institute (NCI)Started 2020-10-28
binimetinibEncorafenib
Solid TumorPrecision Medicine

Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

RECRUITING
NCT06739395Phase PHASE2Tianjin Medical University Second HospitalStarted 2024-11-01
Olaparib tabletTemozolomide capsuleAnlotinib
Breast Cancer, Metastatic Breast Cancer

Next Generation Sequencing-based "Oncochip" for Therapeutic Decision in Metastatic Breast Cancer. Study SHARP

ACTIVE NOT RECRUITING
NCT06727357Phase PHASE2European Institute of OncologyStarted 2019-09-26
Chemotherapy
Hairy Cell Leukemia

Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant

RECRUITING
NCT04322383Phase PHASE2National Cancer Institute (NCI)Started 2021-01-07
binimetinib
Slow-Flow Vascular MalformationFast-Flow Vascular MalformationVascular Malformations

A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations

RECRUITING
NCT05983159Phase PHASE2Murdoch Childrens Research InstituteStarted 2024-09-13
AlpelisibMirdametinib
Refractory Differentiated Thyroid Gland Carcinoma

Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

RECRUITING
NCT06475989Phase PHASE3ECOG-ACRIN Cancer Research GroupStarted 2024-08-22
Biospecimen CollectionCabozantinibComputed Tomography

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients