MAP2K2

Summary

MAP2K2 (mitogen-activated protein kinase kinase 2, HGNC:6842) is a protein-coding gene on chromosome 19p13.3, encoding Dual specificity mitogen-activated protein kinase kinase 2 (P36507). Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases.

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene.

Source: NCBI Gene 5605 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiofaciocutaneous syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 963 total — 7 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 113
• Druggable target: yes — 52 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6842
Approved symbol	MAP2K2
Name	mitogen-activated protein kinase kinase 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MEK2, MKK2
Ensembl gene	ENSG00000126934
Ensembl biotype	protein_coding
OMIM	601263
Entrez	5605

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 16 protein_coding, 7 protein_coding_CDS_not_defined, 6 retained_intron

ENST00000262948, ENST00000394867, ENST00000593364, ENST00000595715, ENST00000597008, ENST00000597263, ENST00000599021, ENST00000599345, ENST00000600584, ENST00000601786, ENST00000602167, ENST00000687128, ENST00000688002, ENST00000688751, ENST00000689792, ENST00000897160, ENST00000897161, ENST00000897162, ENST00000897163, ENST00000897164, ENST00000897165, ENST00000897166, ENST00000920057, ENST00000920058, ENST00000920059, ENST00000945859, ENST00000945860, ENST00000945861, ENST00000945862

RefSeq mRNA: 1 — MANE Select: NM_030662 NM_030662

CCDS: CCDS12120

Canonical transcript exons

ENST00000262948 — 11 exons

Exon	Start	End
ENSE00001147081	4123784	4124122
ENSE00003028134	4090321	4090708
ENSE00003475449	4117419	4117629
ENSE00003491903	4101019	4101143
ENSE00003522027	4095388	4095449
ENSE00003523377	4097279	4097343
ENSE00003548877	4099201	4099414
ENSE00003634914	4094453	4094498
ENSE00003654028	4110509	4110655
ENSE00003671011	4102376	4102453
ENSE00003692358	4101229	4101280

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 152.1105 / max 868.6627, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178415	133.9264	1825
178416	18.1143	1796
178414	0.0397	3
178413	0.0302	14

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.88	gold quality
right testis	UBERON:0004534	98.78	gold quality
left testis	UBERON:0004533	98.77	gold quality
lower esophagus mucosa	UBERON:0035834	98.71	gold quality
apex of heart	UBERON:0002098	98.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.59	gold quality
gastrocnemius	UBERON:0001388	98.26	gold quality
right frontal lobe	UBERON:0002810	98.14	gold quality
adenohypophysis	UBERON:0002196	98.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.96	gold quality
prefrontal cortex	UBERON:0000451	97.95	gold quality
muscle of leg	UBERON:0001383	97.89	gold quality
granulocyte	CL:0000094	97.87	gold quality
stromal cell of endometrium	CL:0002255	97.78	gold quality
cerebellar hemisphere	UBERON:0002245	97.75	gold quality
cerebellar cortex	UBERON:0002129	97.73	gold quality
pituitary gland	UBERON:0000007	97.72	gold quality
transverse colon	UBERON:0001157	97.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.64	gold quality
left adrenal gland cortex	UBERON:0035825	97.61	gold quality
right adrenal gland	UBERON:0001233	97.58	gold quality
amygdala	UBERON:0001876	97.58	gold quality
right ovary	UBERON:0002118	97.57	gold quality
right adrenal gland cortex	UBERON:0035827	97.54	gold quality
left adrenal gland	UBERON:0001234	97.52	gold quality
ventricular zone	UBERON:0003053	97.52	gold quality
cingulate cortex	UBERON:0003027	97.51	gold quality
anterior cingulate cortex	UBERON:0009835	97.46	gold quality
adrenal cortex	UBERON:0001235	97.44	gold quality
ganglionic eminence	UBERON:0004023	97.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FOS	Activation

Upstream regulators (CollecTRI, top): ATF1, ELF4, ESR1, NFKB

miRNA regulators (miRDB)

7 targeting MAP2K2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-4722-5P	98.46	66.34	1611

Literature-anchored findings (GeneRIF, showing 40)

• MEK2 interacts with ERK1. This interaction is mediated via a conserved N-terminal docking site in MEK2. (PMID:11134045)
• MEK2 interacts with ERK2. This interaction is mediated via a conserved N-terminal docking site in MEK2. Note that this interaction was demonstrated using rat ERK2. (PMID:11134045)
• MEK2 activity ad dual-phosphorylation were undetectable in expanding and self-renewing hematopoietic progenitors (HP). Adding IL-3, inducing maturation and cell death in HP, led to sustained high levels of MEK2 activity and dual-phosphorylation. (PMID:12032872)
• Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells. (PMID:12063167)
• MEK2 and p38 in IFN-gamma-mediated signal transduction and induction of C/EBP beta expression and activity associated with interleukin-6 (IL-6) secretion in colon epithelial cells. (PMID:12505790)
• Data show that p-MEK1/2 and p-ERK1/2 are present in neurons in the initial stages of neurofibrillary degeneration in Alzheimer’s disease, before deposition of beta-amyloid. (PMID:12531514)
• MK2 phosphorylates TSC2, which creates a 14-3-3 binding site and thus regulates the cellular function of the TSC2 tumor suppressor protein (PMID:12582162)
• Inhibition of either phosphatidylinositol 3-kinase (PI3-K) or Mek1/2 signaling pathways completely abrogated the IGF-I-induced increase in VEGF secretion and promoter activity (PMID:12612059)
• results show that p38-mediated dephosphorylation of MEK1,2 mediates initiation of apoptosis (PMID:12839928)
• MAPK activated protein kinase-2 mediates both ERK- and p38 MAPK-dependent neutrophil responses. (PMID:14499342)
• HuR and MK2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level (PMID:14517288)
• MEK1,2 response element that mediates angiotensin II-stimulated PAI-1 promoter activation and shows that activation of this element requires Sp1 and AP-1 co-activation. (PMID:14656894)
• Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from O2-. (PMID:14672918)
• Results suggest a physiological link between beta-dystroglycan and mitogen-activated protein kinase kinase 2 (MEK2), and localize MEK with dystroglycan in membrane ruffles. (PMID:15071496)
• Has distinct ways to contribute to a regulated ERK activity and cell cycle progression. (PMID:15284233)
• Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress. (PMID:15292274)
• X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 A and 3.2 A, respectively (PMID:15543157)
• The ability of constitutively-active human MEK2 to stimulate ERK phosphorylation and to induce the neoplastic transformation of NIH 3T3 cells required the integrity of the D-site was found. (PMID:15979847)
• PP2A ABalphaC and ABdeltaC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK1/2 signaling by targeting Raf1 (PMID:16239230)
• a novel signaling pathway involving MKK-2 and ERK1/2 may down-regulate the activity of PABP and eIF4E by controlling their phosphorylation and compensates for the effect of excess cellular PABP (PMID:16332685)
• findings demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase pathway, BRAF, MEK1 and MEK2 cause cardio-facio-cutaneous syndrome (PMID:16439621)
• These data suggest a role for mitochondrially generated reactive oxygen species and Ca(2+) in the redox cell signaling path-ways, leading to ERK activation and adaptation of the pathological stress mediated by oxidized lipids such as lysoPC. (PMID:16651638)
• Taxotere and MEK1/2 inhibitors have the potential to suppress mammary tumor growth in vivo. (PMID:16957420)
• Inhibition of overactive ras-MEK-ERK pathway in HepG2 cells can correct the defect in VLDL assembly leading to the secretion of VLDL-sized particles, similar to primary hepatocytes, implicating the MEK-ERK cascade in VLDL assembly in the HepG2 model. (PMID:17038630)
• MEK1 exports PPARgamma from the nucleus, and this finding was supported by small interfering RNA knockdown of MEK1 and use of a cell-permeable interaction-blocking peptide, which prevented tetradecanoyl phorbol acetate-induced export of PPARgamma. (PMID:17101779)
• mutational analysis of KRAS, BRAF, and MAP2K1/2 in 56 patients with CFC syndrome; comparison of the genotype-phenotype correlation of CFC with that of Costello syndrome suggest a significant clinical overlap but not genotype overlap. (PMID:17366577)
• Mek1/2 are functionally redundant in the epidermis, where they act as a linear relay in the MAPK pathway to mediate development and homeostasis. (PMID:17419998)
• These results indicated that the activation of CXCR4 and its signaling pathways (MEK1/2 and Akt) are essential for CXCL12-induced cholangiocarcinoma cell invasion. (PMID:17461449)
• 3 novel mutations for MEK2 (L46_E55del, K61T, A62P) were identified in 15 patients with cardio-facio-cutaneous syndrome. (PMID:17704260)
• study reports data concerning the biochemical functions of novel MEK1 and MEK2 mutants found in patients with cardio-facio-cutaneous syndrome, as well as the roles of these genes in the MAPK signaling cascade (PMID:17981815)
• the results of HRAS, BRAF and MAP2K1/2 mutation screening in a large cohort of patients with CS and CFC (PMID:18042262)
• BRAF and MEK1/2 mutations may be more common than anticipated in ovarian cancer which could have important implications for treatment of patients with this disease and suggests potential new therapeutic avenues (PMID:18060073)
• Phase I trial of MEK1/2 inhibitor AZD6244 in tumor patients. (PMID:18390968)
• study describes the biochemical characterization of novel BRAF and MEK germline mutations in cardio-facio-cutaneous syndrome (PMID:18413255)
• the induction of inflammatory genes by farnesol is mediated by the activation of the NF-kappaB pathway and involves MEK1/2-ERK1/2-MSK1-dependent phosphorylation of p65/RelA(Ser(276)) (PMID:18424438)
• Esophageal cells from GERD patients with Barrett’s esophagus have elevated MEK1 phosphorylation and decreased MEK1/MEK2 activity. (PMID:18617556)
• MEK1 & MEK2 isoforms have similar transforming properties & are able to induce formation of metastatic intestinal tumors in mice; results suggest MEK2 plays a more important role than MEK1 in sustaining proliferation of human colorectal cancer cells (PMID:19014680)
• Spectrum of MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations (PMID:19156172)
• MEK1/2 phosphorylates ERK1/2, which phosphorylates Sp1 and AP-1 that in turn bind to their respective binding sites to regulate the expression of human VIL2 in ESCC cells. (PMID:19164283)
• SGK1 expression during liver regeneration is a part of a signaling pathway that is necessary for enhancing ERK signaling activation through modulating the MEK/ERK complex formation. (PMID:19447520)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	map2k2a	ENSDARG00000006609
danio_rerio	map2k2b	ENSDARG00000068918
mus_musculus	Map2k2	ENSMUSG00000035027
rattus_norvegicus	Map2k2	ENSRNOG00000020005
drosophila_melanogaster	Dsor1	FBGN0010269
caenorhabditis_elegans	mek-2	WBGENE00003186

Paralogs (8): MAP2K4 (ENSG00000065559), MAP2K7 (ENSG00000076984), MAP3K4 (ENSG00000085511), NEK1 (ENSG00000137601), MAP2K5 (ENSG00000137764), MAP2K1 (ENSG00000169032), MAP3K2 (ENSG00000169967), MAP3K3 (ENSG00000198909)

Protein

Protein identifiers

Dual specificity mitogen-activated protein kinase kinase 2 — P36507 (reviewed: P36507)

Alternative names: ERK activator kinase 2, MAPK/ERK kinase 2

All UniProt accessions (2): P36507, M0R1B6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation.

Subunit / interactions. Interacts with MORG1. Interacts with SGK1. Interacts with KSR1. Interacts with KSR1 and BRAF; the interaction with KSR1 mediates KSR1-BRAF dimerization. Interacts with GLS.

Subcellular location. Cytoplasm. Membrane.

Post-translational modifications. MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1). Phosphorylated by MAP2K1/MEK1. (Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.

Disease relevance. Cardiofaciocutaneous syndrome 4 (CFC4) [MIM:615280] A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

RefSeq proteins (1): NP_109587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050915	MAP_kinase_kinase	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.12.2 — mitogen-activated protein kinase kinase (BRENDA: 38 organisms, 149 substrates, 134 inhibitors, 6 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0533	1
ERK2	0.0002	1
K52R-[ERK2]	0.0001	1
K53M-[P38ALPHA]	0.0002	1
P38ALPHA	0.0002	1

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (48 total): helix 15, modified residue 11, strand 7, sequence variant 4, turn 3, binding site 2, chain 1, domain 1, region of interest 1, sequence conflict 1, active site 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4H3Q	X-RAY DIFFRACTION	2.2
1S9I	X-RAY DIFFRACTION	3.2
1JKY	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36507-F1	82.54	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 194 (proton acceptor); 10–11 (cleavage; by anthrax lethal factor)

Ligand- & substrate-binding residues (2): 78–86; 101

Post-translational modifications (11): 222, 226, 226, 293, 295, 306, 394, 396, 1, 23, 222

Function

Pathways and Gene Ontology

Reactome pathways

36 pathways

ID	Pathway
R-HSA-112411	MAPK1 (ERK2) activation
R-HSA-170968	Frs2-mediated activation
R-HSA-445144	Signal transduction by L1
R-HSA-5210891	Uptake and function of anthrax toxins
R-HSA-5673000	RAF activation
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-5674499	Negative feedback regulation of MAPK pathway
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9652169	Signaling by MAP2K mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166520	Signaling by NTRKs
R-HSA-169893	Prolonged ERK activation events
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-187687	Signalling to ERKs
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-5339562	Uptake and actions of bacterial toxins
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5663205	Infectious disease
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-5683057	MAPK family signaling cascades

MSigDB gene sets: 723 (showing top): PID_SHP2_PATHWAY, MORF_MTA1, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, GOBP_EPITHELIUM_DEVELOPMENT, BIOCARTA_FMLP_PATHWAY, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, BIOCARTA_MAL_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, KEGG_MAPK_SIGNALING_PATHWAY, PID_NETRIN_PATHWAY, GOBP_PEPTIDYL_SERINE_MODIFICATION, BIOCARTA_BARRESTIN_SRC_PATHWAY, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_LUNG_MORPHOGENESIS

GO Biological Process (24): MAPK cascade (GO:0000165), heart development (GO:0007507), positive regulation of gene expression (GO:0010628), Schwann cell development (GO:0014044), thyroid gland development (GO:0030878), regulation of stress-activated MAPK cascade (GO:0032872), peptidyl-serine autophosphorylation (GO:0036289), ERBB2-ERBB3 signaling pathway (GO:0038133), myelination (GO:0042552), positive regulation of DNA-templated transcription (GO:0045893), insulin-like growth factor receptor signaling pathway (GO:0048009), thymus development (GO:0048538), regulation of axon regeneration (GO:0048679), positive regulation of axonogenesis (GO:0050772), face development (GO:0060324), trachea formation (GO:0060440), epithelial cell proliferation involved in lung morphogenesis (GO:0060502), ERK1 and ERK2 cascade (GO:0070371), positive regulation of protein serine/threonine kinase activity (GO:0071902), regulation of Golgi inheritance (GO:0090170), positive regulation of cell motility (GO:2000147), regulation of early endosome to late endosome transport (GO:2000641), protein phosphorylation (GO:0006468), lung morphogenesis (GO:0060425)

GO Molecular Function (17): protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase activity (GO:0004708), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), MAP kinase scaffold activity (GO:0005078), ATP binding (GO:0005524), PDZ domain binding (GO:0030165), protein serine/threonine kinase activator activity (GO:0043539), metal ion binding (GO:0046872), scaffold protein binding (GO:0097110), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), molecular adaptor activity (GO:0060090)

GO Cellular Component (19): extracellular region (GO:0005576), nucleus (GO:0005634), mitochondrion (GO:0005739), early endosome (GO:0005769), late endosome (GO:0005770), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), microtubule (GO:0005874), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), perinuclear region of cytoplasm (GO:0048471), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Oncogenic MAPK signaling	6
RAF/MAP kinase cascade	2
RAF-independent MAPK1/3 activation	1
Prolonged ERK activation events	1
L1CAM interactions	1
Uptake and actions of bacterial toxins	1
Negative regulation of MAPK pathway	1
Signaling by RAS mutants	1
MAPK1/MAPK3 signaling	1
Signaling by Receptor Tyrosine Kinases	1
Signalling to ERKs	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cytoplasm	5
protein kinase activity	4
intracellular membrane-bounded organelle	4
MAPK cascade	3
sperm flagellum	3
gland development	2
protein serine/threonine kinase activity	2
binding	2
endosome	2
endomembrane system	2
intracellular signaling cassette	1
animal organ development	1
circulatory system development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
Schwann cell differentiation	1
glial cell development	1
endocrine system development	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1
peptidyl-serine phosphorylation	1
protein autophosphorylation	1
ERBB2 signaling pathway	1
ERBB3 signaling pathway	1
axon ensheathment	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
hematopoietic or lymphoid organ development	1
axon regeneration	1
regulation of response to external stimulus	1
regulation of neuron projection regeneration	1
regulation of response to wounding	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1

Protein interactions and networks

STRING

2974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP2K2	MAPK1	P28482	856
MAP2K2	BRAF	P15056	836
MAP2K2	MAP2K1	Q02750	783
MAP2K2	SOS1	Q07889	778
MAP2K2	CTNNB1	P35222	750
MAP2K2	PTPN11	Q06124	728
MAP2K2	SHOC2	Q9UQ13	685
MAP2K2	GRB2	P29354	681
MAP2K2	NRAS	P01111	655
MAP2K2	HRAS	P01112	641
MAP2K2	KSR1	Q8IVT5	627
MAP2K2	KRAS	P01116	625
MAP2K2	SGK1	O00141	620
MAP2K2	MAPK3	P27361	600
MAP2K2	JUN	P05412	587

IntAct

417 interactions, top by confidence:

A	B	Type	Score
MAP2K1	RAF1	psi-mi:“MI:0914”(association)	0.960
BRAF	HRAS	psi-mi:“MI:0914”(association)	0.940
NRAS	RAF1	psi-mi:“MI:0914”(association)	0.930
MAP2K2	ARAF	psi-mi:“MI:0915”(physical association)	0.910
ARAF	MAP2K2	psi-mi:“MI:0915”(physical association)	0.910
MAP2K2	ARAF	psi-mi:“MI:0407”(direct interaction)	0.910
BRAF	MAP2K2	psi-mi:“MI:0915”(physical association)	0.890
MAP2K2	BRAF	psi-mi:“MI:0915”(physical association)	0.890
BRAF	MAP2K2	psi-mi:“MI:0914”(association)	0.890
BRAF	MAP2K2	psi-mi:“MI:2364”(proximity)	0.890
BRAF	NRAS	psi-mi:“MI:0914”(association)	0.860
MAP2K2	RAF1	psi-mi:“MI:0915”(physical association)	0.850
RAF1	MAP2K2	psi-mi:“MI:0915”(physical association)	0.850
MAP2K2	RAF1	psi-mi:“MI:0914”(association)	0.850
KSR1	MAP2K2	psi-mi:“MI:0915”(physical association)	0.800
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BRAF	KRAS	psi-mi:“MI:0914”(association)	0.680
MAP2K2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.680
MAP4K1	HSP90AB1	psi-mi:“MI:0914”(association)	0.670
MAP2K2	TUBA4A	psi-mi:“MI:0914”(association)	0.640
KSR2	MAP2K2	psi-mi:“MI:0914”(association)	0.640

BioGRID (398): MAP2K2 (Affinity Capture-Western), MAP2K2 (Two-hybrid), CCNDBP1 (Two-hybrid), MAP2K2 (Affinity Capture-MS), MAP2K2 (Affinity Capture-MS), MAP2K2 (Affinity Capture-MS), MAP2K2 (Affinity Capture-MS), MAP2K2 (Co-fractionation), MAP2K2 (Co-fractionation), TXN (Co-fractionation), MAP2K2 (Affinity Capture-MS), MAP2K2 (Affinity Capture-Western), MAP2K2 (Affinity Capture-MS), MAP2K2 (Affinity Capture-MS), ARAF (Two-hybrid)

ESM2 similar proteins: A0A1S4CGX4, A9RWC9, A9S5R3, A9SR33, O01775, O14047, O14733, O44408, O80396, P10506, P18652, P18654, P29678, P31938, P36506, P36507, P51812, Q01986, Q02750, Q03428, Q05116, Q08942, Q10664, Q13163, Q18846, Q1HG70, Q20347, Q21307, Q24324, Q4KSH7, Q4V3C8, Q5QN75, Q62862, Q63932, Q63980, Q7TPS0, Q8MXI4, Q91447, Q94A06, Q99JT2

Diamond homologs: A0A194VNL2, A0A1S4CGX4, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, A9RWC9, A9S5R3, A9SR33, B0XPE4, C4YLK8, E1BK52, F1NBT0, G4N6Z6, G4NEB8, G5EDF7, O00506, O09110, O14733, O54748, O80396, O94804, O95819, P06784, P08018, P0CY25, P10506, P29678, P31938, P32490, P32491, P33886, P36506, P36507, P45985, P46734

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
2-(2-amino-3-methoxyphenyl)chromen-4-one	down-regulates	MAP2K2	“chemical inhibition”
SL-327	down-regulates	MAP2K2	“chemical inhibition”
U0126	down-regulates	MAP2K2	“chemical inhibition”
PDPK1	up-regulates	MAP2K2	phosphorylation
MAP3K8	up-regulates	MAP2K2	phosphorylation
PPP2CA	down-regulates	MAP2K2	dephosphorylation
ARAF	up-regulates	MAP2K2	phosphorylation
MAP2K2	up-regulates	PPARG	binding
N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamide	down-regulates	MAP2K2	“chemical inhibition”
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide	down-regulates	MAP2K2	“chemical inhibition”
MAP2K2	up-regulates	MAPK3	phosphorylation
trametinib	down-regulates	MAP2K2	“chemical inhibition”
PD318088	down-regulates	MAP2K2	“chemical inhibition”
U0126.EtOH	down-regulates	MAP2K2	“chemical inhibition”
MAP2K2	up-regulates	ERK1/2	phosphorylation
trametinib	“down-regulates activity”	MAP2K2	“chemical inhibition”
RAF1	up-regulates	MAP2K2	phosphorylation
MAP2K2	up-regulates	Gbeta	phosphorylation
BRAF	up-regulates	MAP2K2	phosphorylation
MAP2K2	up-regulates	MAPK1	phosphorylation
MAP2K2	“up-regulates activity”	ERK1/2	phosphorylation
MAP2K2	“up-regulates activity”	MAPK1	phosphorylation
MAP2K2	“up-regulates activity”	MAPK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	43.0×	7e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	37.9×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.9×	2e-08
Ras activation upon Ca2+ influx through NMDA receptor	7	32.2×	5e-08
Signaling by high-kinase activity BRAF mutants	12	30.7×	1e-12
Constitutive Signaling by EGFRvIII	5	28.8×	2e-05
Activation of BH3-only proteins	7	28.0×	1e-07
MAP2K and MAPK activation	12	27.6×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to synapse	5	24.4×	3e-04
establishment or maintenance of epithelial cell apical/basal polarity	6	22.2×	2e-04
protein refolding	5	19.9×	6e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	18.9×	2e-04
response to heat	6	16.1×	3e-04
protein targeting	6	14.0×	6e-04
cellular response to heat	6	13.1×	7e-04
ERK1 and ERK2 cascade	6	12.2×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

963 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	9
Uncertain significance	408
Likely benign	347
Benign	95

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1495968	NM_030662.4(MAP2K2):c.395G>T (p.Gly132Val)	Pathogenic
254207	NM_030662.4(MAP2K2):c.210_212del (p.Asp71del)	Pathogenic
578970	NM_030662.4(MAP2K2):c.171T>A (p.Phe57Leu)	Pathogenic
8272	NM_030662.4(MAP2K2):c.170T>G (p.Phe57Cys)	Pathogenic
8273	NM_030662.4(MAP2K2):c.169T>G (p.Phe57Val)	Pathogenic
8274	NM_030662.4(MAP2K2):c.400T>C (p.Tyr134His)	Pathogenic
8275	NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)	Pathogenic
177868	NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys)	Likely pathogenic
180912	NM_030662.4(MAP2K2):c.190G>T (p.Val64Phe)	Likely pathogenic
1963465	NM_030662.4(MAP2K2):c.334C>T (p.Arg112Trp)	Likely pathogenic
2444198	NM_030662.4(MAP2K2):c.167C>A (p.Ala56Asp)	Likely pathogenic
3364401	NM_030662.4(MAP2K2):c.368A>C (p.His123Pro)	Likely pathogenic
40813	NM_030662.4(MAP2K2):c.619G>A (p.Glu207Lys)	Likely pathogenic
4294094	NM_030662.4(MAP2K2):c.180G>C (p.Gln60His)	Likely pathogenic
431174	NM_030662.4(MAP2K2):c.191T>G (p.Val64Gly)	Likely pathogenic
666424	NM_030662.4(MAP2K2):c.187_192del (p.Lys63_Val64del)	Likely pathogenic

SpliceAI

2722 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4090709:C:CC	acceptor_gain	1.0000
19:4094451:A:AC	donor_gain	1.0000
19:4094452:C:CC	donor_gain	1.0000
19:4094522:C:CT	acceptor_gain	1.0000
19:4094523:G:T	acceptor_gain	1.0000
19:4094529:C:CT	acceptor_gain	1.0000
19:4094530:G:T	acceptor_gain	1.0000
19:4094531:G:C	acceptor_gain	1.0000
19:4094531:G:GC	acceptor_gain	1.0000
19:4095445:GGTGG:G	acceptor_gain	1.0000
19:4095447:TGG:T	acceptor_gain	1.0000
19:4095448:GG:G	acceptor_gain	1.0000
19:4095448:GGC:G	acceptor_loss	1.0000
19:4095450:C:A	acceptor_loss	1.0000
19:4095450:C:CC	acceptor_gain	1.0000
19:4095451:T:G	acceptor_loss	1.0000
19:4095452:G:C	acceptor_gain	1.0000
19:4095452:G:GC	acceptor_gain	1.0000
19:4099427:C:CT	acceptor_gain	1.0000
19:4101017:A:AC	donor_gain	1.0000
19:4101017:ACAG:A	donor_gain	1.0000
19:4101017:ACAGC:A	donor_gain	1.0000
19:4101018:C:CC	donor_gain	1.0000
19:4101018:CAG:C	donor_gain	1.0000
19:4101018:CAGC:C	donor_gain	1.0000
19:4101018:CAGCC:C	donor_gain	1.0000
19:4102371:CTCA:C	donor_loss	1.0000
19:4102372:TCA:T	donor_loss	1.0000
19:4102373:CACCG:C	donor_loss	1.0000
19:4102374:A:AC	donor_gain	1.0000

AlphaMissense

2619 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4097298:A:G	L322P	1.000
19:4097301:A:G	L321P	1.000
19:4097307:A:C	F319C	1.000
19:4099359:C:T	G254D	1.000
19:4099360:C:G	G254R	1.000
19:4099364:G:C	S252R	1.000
19:4099364:G:T	S252R	1.000
19:4099366:T:G	S252R	1.000
19:4099369:A:G	W251R	1.000
19:4099369:A:T	W251R	1.000
19:4099375:C:A	D249Y	1.000
19:4099375:C:G	D249H	1.000
19:4099404:A:G	L239S	1.000
19:4101023:A:G	M234T	1.000
19:4101038:C:T	G229D	1.000
19:4101039:C:G	G229R	1.000
19:4101043:G:C	F227L	1.000
19:4101043:G:T	F227L	1.000
19:4101044:A:C	F227C	1.000
19:4101044:A:G	F227S	1.000
19:4101045:A:G	F227L	1.000
19:4101047:G:A	S226F	1.000
19:4101048:A:G	S226P	1.000
19:4101053:G:T	A224D	1.000
19:4101060:A:G	S222P	1.000
19:4101068:A:G	L219P	1.000
19:4101076:G:C	S216R	1.000
19:4101076:G:T	S216R	1.000
19:4101078:T:G	S216R	1.000
19:4101083:C:T	G214E	1.000

dbSNP variants (sampled 300 via entrez): RS1000084852 (19:4108642 C>T), RS1000088971 (19:4108848 G>A,T), RS1000145479 (19:4107831 C>T), RS1000173427 (19:4122103 C>G), RS1000223458 (19:4115825 C>T), RS1000278035 (19:4090302 A>C), RS1000398062 (19:4091734 T>A), RS1000418616 (19:4104005 T>C), RS1000450256 (19:4111480 C>T), RS1000628312 (19:4123498 T>A,C), RS1000680437 (19:4115659 A>C), RS1000695147 (19:4121510 C>T), RS1000741356 (19:4093096 C>A), RS1000812393 (19:4102962 C>A,T), RS1000867343 (19:4096516 C>G)

Disease associations

OMIM: gene MIM:601263 | disease phenotypes: MIM:615280, MIM:163950, MIM:115150, MIM:601321, MIM:151100

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiofaciocutaneous syndrome 4	Definitive	Autosomal dominant
cardiofaciocutaneous syndrome	Definitive	Autosomal dominant
neurofibromatosis-Noonan syndrome	Supportive	Autosomal dominant
Noonan syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Noonan syndrome	Limited	AD
cardiofaciocutaneous syndrome	Definitive	AD

Mondo (14): RASopathy (MONDO:0021060), cardiofaciocutaneous syndrome 4 (MONDO:0014114), Noonan syndrome and Noonan-related syndrome (MONDO:0020297), Noonan syndrome 1 (MONDO:0008104), cardiofaciocutaneous syndrome (MONDO:0015280), Noonan syndrome (MONDO:0018997), cardiofaciocutaneous syndrome 1 (MONDO:0007265), neurofibromatosis-Noonan syndrome (MONDO:0011035), Noonan syndrome with multiple lentigines (MONDO:0007893), hypertrophic cardiomyopathy (MONDO:0005045), mitral valve prolapse (MONDO:0004910), migraine disorder (MONDO:0005277), hypotensive disorder (MONDO:0005468), Castleman-Kojima disease (MONDO:0018702)

Orphanet (8): RASopathy (Orphanet:536391), Cardiofaciocutaneous syndrome (Orphanet:1340), Noonan syndrome and Noonan-related syndrome (Orphanet:98733), Noonan syndrome (Orphanet:648), Neurofibromatosis-Noonan syndrome (Orphanet:638), Noonan syndrome with multiple lentigines (Orphanet:500), Rare hypertrophic cardiomyopathy (Orphanet:217569), TAFRO syndrome (Orphanet:457077)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000176	Submucous cleft hard palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000271	Abnormality of the face
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000336	Prominent supraorbital ridges
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000391	Thickened helices
HP:0000400	Macrotia
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000504	Abnormality of vision
HP:0000506	Telecanthus

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005908_38	Height	7.000000e-12
GCST006629_17	Pulse pressure	1.000000e-12
GCST006979_740	Heel bone mineral density	2.000000e-09
GCST90002381_244	Eosinophil count	8.000000e-14
GCST90002388_31	Lymphocyte count	4.000000e-10
GCST90002407_353	White blood cell count	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0004842	eosinophil count
EFO:0004587	lymphocyte count

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D007022	Hypotension	C14.907.514
D044542	LEOPARD Syndrome	C05.660.207.525; C14.240.400.695; C14.280.400.695; C14.280.484.716.525; C16.131.077.525; C16.131.240.400.685; C16.131.621.207.525; C17.800.621.430.530.550.525
D008881	Migraine Disorders	C10.228.140.546.399.750
D008945	Mitral Valve Prolapse	C14.280.484.400.500
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690
C535579	Cardiofaciocutaneous syndrome (supp.)
C537393	Neurofibromatosis-Noonan syndrome (supp.)
C537846	Noonan like syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2111289 (PROTEIN FAMILY), CHEMBL2964 (SINGLE PROTEIN), CHEMBL4523690 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523734 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523755 (PROTEIN-PROTEIN INTERACTION), CHEMBL4742286 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

52 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 257,155 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1614701	SELUMETINIB	4	10,221
CHEMBL2103875	TRAMETINIB	4	14,034
CHEMBL2146883	COBIMETINIB	4	9,422
CHEMBL3187723	BINIMETINIB	4	7,280
CHEMBL5416410	DASATINIB	4	655
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL3264002	AVUTOMETINIB	3	2,208
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL105442	CI-1040	2
CHEMBL507361	MIRDAMETINIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL1236682	REFAMETINIB	2
CHEMBL1615025	TAK-733	2
CHEMBL1721885	SU-014813	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — STE7 family

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
trametinib	Inhibition	8.74	pIC50
BI-847325	Inhibition	8.4	pIC50
binimetinib	Negative	7.92	pIC50
refametinib	Negative	7.33	pIC50
voruciclib	Inhibition	7.06	pIC50
cobimetinib	Negative	6.7	pIC50
MEK1/2 inhibitor	Inhibition	6.66	pIC50
MS432	Inhibition	6.23	pIC50

Binding affinities (BindingDB)

13 measured of 13 human assays (13 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

394 potent at pChembl≥5 of 436 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	COBIMETINIB
9.32	IC50	0.48	nM	TRAMETINIB
9.28	IC50	0.52	nM	TRAMETINIB
9.05	IC50	0.9	nM	CHEMBL450775
9.04	IC50	0.92	nM	TRAMETINIB
8.92	IC50	1.2	nM	CHEMBL244488
8.85	IC50	1.4	nM	CHEMBL3182051
8.80	IC50	1.6	nM	TRAMETINIB
8.74	IC50	1.8	nM	TRAMETINIB
8.70	IC50	2	nM	CHEMBL244488
8.70	IC50	2	nM	TRAMETINIB
8.67	IC50	2.16	nM	TRAMETINIB
8.66	IC50	2.2	nM	TRAMETINIB
8.64	IC50	2.3	nM	TRAMETINIB
8.46	IC50	3.5	nM	CI-1040
8.43	IC50	3.7	nM	CHEMBL2146893
8.41	Kd	3.9	nM	LESTAURTINIB
8.40	IC50	4	nM	CHEMBL442235
8.40	IC50	4	nM	CHEMBL3699142
8.39	IC50	4.1	nM	TRAMETINIB
8.30	IC50	5	nM	CHEMBL234887
8.24	IC50	5.7	nM	TRAMETINIB
8.22	Kd	6	nM	RO-4987655
8.22	IC50	6	nM	CHEMBL1933935
8.20	Ki	6.31	nM	CHEMBL1976376
8.16	IC50	6.9	nM	CHEMBL2146892
8.15	IC50	7	nM	AZD-8330
8.15	IC50	7	nM	CHEMBL1933934
8.10	IC50	8	nM	CHEMBL1933937
8.09	IC50	8.16	nM	CHEMBL2012519
8.07	IC50	8.5	nM	TRAMETINIB
8.05	Kd	9	nM	TRAMETINIB
8.05	IC50	9	nM	CHEMBL3590107
8.05	IC50	9	nM	CHEMBL1933928
8.05	IC50	9	nM	CHEMBL1933932
8.00	Kd	9.9	nM	BOSUTINIB
7.96	IC50	11	nM	CHEMBL2146894
7.92	Kd	12	nM	MIRDAMETINIB
7.92	IC50	12	nM	BINIMETINIB
7.90	Kd	12.7	nM	CHEMBL3752910
7.90	ED50	12.7	nM	CHEMBL3752910
7.90	IC50	12.7	nM	TRAMETINIB
7.89	Kd	13	nM	FORETINIB
7.89	IC50	13	nM	CHEMBL1933923
7.86	IC50	13.7	nM	MIRDAMETINIB
7.85	IC50	14	nM	CHEMBL2146895
7.85	IC50	14	nM	SELUMETINIB
7.85	IC50	14	nM	MIRDAMETINIB
7.85	IC50	14	nM	CHEMBL1933931
7.85	IC50	14	nM	CHEMBL1933938

PubChem BioAssay actives

246 with measured affinity, of 1482 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Cobimetinib	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0002	uM
N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0009	uM
Trametinib	1697076: Inhibition of MEK in human KYSE-520 cells assessed as reduction in p-ERK levels	ic50	0.0010	uM
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide	298460: Inhibition of MEK assessed as inhibition of ERK phosphorylation by Raf-MEK-ERK cascade assay	ic50	0.0012	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(propan-2-ylamino)methyl]azetidin-1-yl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0037	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507613: Binding affinity to MEK2	kd	0.0039	uM
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxopyridine-3-carboxamide	298461: Inhibition of MEK in mouse colon 26 carcinoma cells assessed as inhibition of ERK phosphorylation by ELISA	ic50	0.0040	uM
3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide	1851106: Inhibition of human MEK2	ic50	0.0040	uM
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxopyridine-3-carboxamide	298461: Inhibition of MEK in mouse colon 26 carcinoma cells assessed as inhibition of ERK phosphorylation by ELISA	ic50	0.0050	uM
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM
N-[(2R)-2,3-dihydroxypropoxy]-2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0060	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-(ethylaminomethyl)-3-hydroxyazetidin-1-yl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0069	uM
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0070	uM
2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-N-[(3R)-pyrrolidin-3-yl]-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0080	uM
(4S,6Z,9S,10S)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,15,17-tetraene-2,8-dione	1431755: Inhibition of human MEK2 using ERK2 as substrate in presence of [gamma-33P]-ATP by scintillation counting method	ic50	0.0082	uM
(3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide	1626507: Inhibition of MEK in human A375 cells assessed as inhibition of ERK phosphorylation	ic50	0.0090	uM
2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0090	uM
2-(2-chloro-4-iodoanilino)-N-[(2R)-2,3-dihydroxypropoxy]-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0090	uM
Bosutinib	625137: Binding constant for MEK2 kinase domain	kd	0.0099	uM
[3-[(tert-butylamino)methyl]-3-hydroxyazetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0110	uM
Binimetinib	2141019: Inhibition of MEK1/2 (unknown origin)	ic50	0.0120	uM
mirdametinib	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0120	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148685: Binding affinity to human MAP2K2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0127	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625137: Binding constant for MEK2 kinase domain	kd	0.0130	uM
2-(2-chloro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0130	uM
Selumetinib	1724031: Inhibition of MEK (unknown origin)	ic50	0.0140	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-[(dimethylamino)methyl]-3-hydroxyazetidin-1-yl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0140	uM
N-(2-amino-2-methylpropyl)-2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0140	uM
2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxylic acid	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0140	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715282: Inhibition of human MEK2 using ERK2 as substrate by [gamma-33P]-ATP assay	ic50	0.0146	uM
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0150	uM
10,11-difluoro-12-(2-fluoro-4-iodoanilino)-2,2-dioxospiro[4,5,6,7-tetrahydro-1H-8,2lambda6,1-benzoxathiazecine-3,1’-cyclopropane]-5,6-diol	1336710: Inhibition of MEK1/2 in human HT-29 cells assessed as reduction in cell proliferation after 72 hrs by CellTiter-Glo assay	ic50	0.0160	uM
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide	298460: Inhibition of MEK assessed as inhibition of ERK phosphorylation by Raf-MEK-ERK cascade assay	ic50	0.0160	uM
3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide	298460: Inhibition of MEK assessed as inhibition of ERK phosphorylation by Raf-MEK-ERK cascade assay	ic50	0.0174	uM
N-(2-amino-2-methylpropyl)-2-(2-chloro-4-iodoanilino)-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0180	uM
3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0200	uM
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxopyridine-3-carboxamide	298461: Inhibition of MEK in mouse colon 26 carcinoma cells assessed as inhibition of ERK phosphorylation by ELISA	ic50	0.0210	uM
2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-N-[(3R)-piperidin-3-yl]-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0220	uM
Neratinib	625137: Binding constant for MEK2 kinase domain	kd	0.0260	uM
2-(2-chloro-4-iodoanilino)-N-[(2R)-2,3-dihydroxypropyl]-5,5-dimethyl-8-oxo-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0280	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxyazetidin-1-yl)methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0290	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-(hydroxymethyl)azetidin-1-yl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0290	uM
3-[[3-fluoro-2-(methylsulfamoylamino)-4-pyridinyl]methyl]-4-methyl-7-pyrimidin-2-yloxychromen-2-one	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0370	uM
N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)pyridine-4-carboxamide	1425039: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0380	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625137: Binding constant for MEK2 kinase domain	kd	0.0420	uM
2-(2-fluoro-4-iodoanilino)-5,5-dimethyl-8-oxo-N-[[(2R)-pyrrolidin-2-yl]methyl]-6,7-dihydro-4H-thieno[2,3-c]azepine-3-carboxamide	638310: Inhibition of human MEK using fluorescein-labelled Erk-tide as substrate after 20 mins by IMAP assay	ic50	0.0420	uM
[3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0460	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-(pyrrolidin-1-ylmethyl)azetidin-1-yl]methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0500	uM
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxy-3-methylazetidin-1-yl)methanone	689334: Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting	ic50	0.0510	uM
N-[(R)-cyclopropyl(pyridin-2-yl)methyl]-3-[4-[(1S,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]phenyl]-1H-indazole-5-carboxamide	1203313: Inhibition of MAPK2 (unknown origin) by millipore radiometric assay	ic50	0.0570	uM

CTD chemical–gene interactions

139 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
U 0126	decreases activity, affects cotreatment, increases response to substance, decreases response to substance	7
bisphenol A	increases methylation, decreases expression, increases expression, affects expression, affects cotreatment	5
sodium arsenite	decreases reaction, increases phosphorylation, affects expression, increases expression, increases activity	4
Arsenic Trioxide	decreases activity, increases expression, decreases reaction, increases activity, increases phosphorylation (+2 more)	4
Tetradecanoylphorbol Acetate	affects cotreatment, decreases expression, increases phosphorylation, increases reaction, decreases reaction (+1 more)	4
Sorafenib	increases phosphorylation, decreases phosphorylation, affects cotreatment, decreases reaction	3
Benzo(a)pyrene	affects cotreatment, increases phosphorylation, affects methylation, decreases reaction	3
Ozone	increases expression, affects cotreatment, increases oxidation, affects expression, increases abundance (+2 more)	3
decabromobiphenyl ether	decreases phosphorylation, decreases reaction, decreases expression, increases phosphorylation	2
vanadyl sulfate	decreases reaction, increases phosphorylation, increases activity	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases phosphorylation, increases reaction	2
Chenodeoxycholic Acid	affects cotreatment, increases expression	2
Cisplatin	increases phosphorylation, affects cotreatment, decreases response to substance, decreases activity, increases response to substance	2
Deoxycholic Acid	affects cotreatment, increases expression	2
Estradiol	increases expression, increases phosphorylation, decreases reaction	2
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	2
Glycocholic Acid	affects cotreatment, increases expression	2
Glycodeoxycholic Acid	affects cotreatment, increases expression	2
Lead	decreases expression, increases phosphorylation	2
Tretinoin	decreases reaction, increases activity, increases phosphorylation, increases reaction	2
Zinc Sulfate	decreases reaction, increases phosphorylation, increases activity	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects expression, affects cotreatment	1
geldanamycin	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases reaction, increases activity, increases phosphorylation	1

ChEMBL screening assays

615 unique, capped per target: 581 binding, 33 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042543	Binding	Inhibition of MEK1/2 phosphorylation in PMA-stimulated human U937 cells at 50 uM after 3 hrs by Western blotting	Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors. — Bioorg Med Chem Lett
CHEMBL4124007	ADMET	Activation of MEK1/2 in EGF-stimulated human MDA-MB-231 cells assessed as increase in pERK1/2 levels preincubated for 30 mins followed by EGF stimulation measured after 15 mins by Western blot analysis relative to control	Structure activity relationships of anthranilic acid-based compounds on cellular and in vivo mitogen activated protein kinase-5 signaling pathways. — Bioorg Med Chem Lett
CHEMBL645947	Functional	AP-1 suppression activity using freshly prepared DMSO stock	MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 transformed cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4IN	VACO 432 MAP2K2 (-/-)	Cancer cell line	Male
CVCL_B3AJ	Abcam HEK293T MAP2K2 KO	Transformed cell line	Female
CVCL_B8K0	Abcam HCT 116 MAP2K2 KO	Cancer cell line	Male
CVCL_B8YH	Abcam MCF-7 MAP2K2 KO	Cancer cell line	Female
CVCL_B9M9	Abcam A-549 MAP2K2 KO	Cancer cell line	Male
CVCL_D8PT	Ubigene HCT 116 MAP2K2 KO	Cancer cell line	Male
CVCL_E0H2	Ubigene HeLa MAP2K2 KO	Cancer cell line	Female
CVCL_F1AF	GM29866	Finite cell line	Female
CVCL_SW39	HAP1 MAP2K2 (-) 1	Cancer cell line	Male
CVCL_SW40	HAP1 MAP2K2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

269 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00452725	PHASE3	COMPLETED	Effect of MAXOMAT ® on the Growth of Small Children to NOONAN’s Syndrome
NCT01529840	PHASE3	COMPLETED	Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome
NCT01529944	PHASE3	COMPLETED	Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658
NCT01927861	PHASE3	COMPLETED	Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT02713945	PHASE3	COMPLETED	Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome
NCT05723835	PHASE3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT05631730	PHASE3	RECRUITING	Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse
NCT00351221	PHASE2	TERMINATED	Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome
NCT06555237	PHASE2	RECRUITING	MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
NCT06668805	PHASE2	RECRUITING	A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy