MAP2K1

mitogen-activated protein kinase kinase 1, the group of Mitogen-activated protein kinase kinases

Basic information

Region (hg38): 15:66386836-66491656

Previous symbols: [ "PRKMK1" ]

Links

ENSG00000169032 ∙ NCBI:5604 ∙ OMIM:176872 ∙ HGNC:6840 ∙ Uniprot:Q02750 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiofaciocutaneous syndrome 3 (Definitive), mode of inheritance: AD
• cardiofaciocutaneous syndrome 1 (Definitive), mode of inheritance: AD
• cardiofaciocutaneous syndrome 3 (Moderate), mode of inheritance: AD
• cardiofaciocutaneous syndrome 3 (Strong), mode of inheritance: AD
• Noonan syndrome with multiple lentigines (Strong), mode of inheritance: AD
• cardiofaciocutaneous syndrome (Supportive), mode of inheritance: AD
• cardiofaciocutaneous syndrome 3 (Strong), mode of inheritance: AD
• Noonan syndrome (Limited), mode of inheritance: AD
• Costello syndrome (Disputed Evidence), mode of inheritance: AD
• Noonan syndrome with multiple lentigines (Limited), mode of inheritance: AD
• cardiofaciocutaneous syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiofaciocutaneous syndrome 3	AD	Cardiovascular; Oncologic	Surveillance and treatment related to manifestations such as cardiac anomalies can be beneficial; Individuals may be at increased malignancy risk (eg, an individual with hepatoplastoma has been described), and awareness may allow prompt recognition and treatment of oncologic sequelae	Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic	16439621; 17551924; 17567882; 18456719; 18042262; 20301303; 20301365; 21495173

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP2K1 gene.

• RASopathy (293 variants)
• not provided (178 variants)
• not specified (83 variants)
• Cardiovascular phenotype (65 variants)
• Cardiofaciocutaneous syndrome 3 (25 variants)
• Noonan syndrome and Noonan-related syndrome (23 variants)
• Cardio-facio-cutaneous syndrome (17 variants)
• Inborn genetic diseases (13 variants)
• Noonan syndrome (11 variants)
• Melanoma (6 variants)
• MAP2K1-related condition (5 variants)
• Cardiofaciocutaneous syndrome 3;Noonan syndrome 1 (4 variants)
• Melorheostosis (3 variants)
• Non-small cell lung carcinoma (3 variants)
• Vascular malformation (3 variants)
• Malignant neoplasm of body of uterus (2 variants)
• Transitional cell carcinoma of the bladder (2 variants)
• Neoplasm of the large intestine (2 variants)
• Malignant melanoma of skin (2 variants)
• Melorheostosis;Cardiofaciocutaneous syndrome 3;Noonan syndrome 1 (1 variants)
• Cardiofaciocutaneous syndrome 3;Melorheostosis (1 variants)
• Melorheostosis;Noonan syndrome 1;Cardiofaciocutaneous syndrome 3 (1 variants)
• MAP2K1-Related Disorder (1 variants)
• Noonan syndrome 1 (1 variants)
• MAP2K1-related RASopathy (1 variants)
• Lung adenocarcinoma (1 variants)
• Parkes Weber syndrome (1 variants)
• MAP2K1-Related Disorders (1 variants)
• Autism spectrum disorder (1 variants)
• Neoplasm (1 variants)
• MAP2K1-related rasopathy-like syndrome (1 variants)
• Noonan syndrome;Cardio-facio-cutaneous syndrome (1 variants)
• Squamous cell lung carcinoma (1 variants)
• Noonan syndrome 1;Melorheostosis;Cardiofaciocutaneous syndrome 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	89	6	99
missense	18	13	125	1	1	158
nonsense			4			4
start loss						0
frameshift			4			4
inframe indel	1	6	4			11
splice donor/acceptor (+/-2bp)			9			9
splice region			12	18	3	33
non coding			8	82	38	128
Total	19	19	158	172	45

Variants in MAP2K1

This is a list of pathogenic ClinVar variants found in the MAP2K1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-66386900-C-T			Likely benign (Jul 31, 2018)
15-66387126-T-TGC		Cardio-facio-cutaneous syndrome • Noonan syndrome	Likely benign (Oct 16, 2018)
15-66387236-G-GGGCCCGC			Likely benign (Nov 15, 2018)
15-66387263-G-C			Benign (Mar 03, 2015)
15-66387305-C-T			Likely benign (Feb 07, 2021)
15-66387311-T-TC		not specified	Benign (Apr 15, 2014)
15-66387346-A-G		not specified • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype • RASopathy	Benign (Nov 17, 2023)
15-66387352-C-G		RASopathy	Uncertain significance (May 17, 2022)
15-66387353-C-G		RASopathy • Cardiovascular phenotype	Likely benign (Oct 02, 2023)
15-66387353-C-T		not specified • RASopathy • Noonan syndrome and Noonan-related syndrome • Cardiovascular phenotype	Benign/Likely benign (Nov 27, 2023)
15-66387356-G-A		RASopathy	Likely benign (Dec 22, 2023)
15-66387358-A-G		RASopathy	Uncertain significance (Jan 14, 2023)
15-66387359-G-A		RASopathy • Cardiovascular phenotype	Likely benign (Nov 02, 2023)
15-66387362-G-A		not specified • RASopathy	Likely benign (May 28, 2022)
15-66387362-G-T		MAP2K1-related disorder	Uncertain significance (Nov 30, 2023)
15-66387376-A-T		not specified	Uncertain significance (Aug 12, 2019)
15-66387378-C-G		RASopathy	Uncertain significance (Dec 19, 2023)
15-66387380-G-A		RASopathy	Likely benign (Jul 14, 2022)
15-66387383-C-T			Likely benign (Jun 25, 2018)
15-66387384-C-T			Uncertain significance (Sep 20, 2022)
15-66387386-G-A		not specified • RASopathy	Likely benign (Apr 07, 2022)
15-66387387-GC-G			Uncertain significance (Sep 16, 2018)
15-66387388-C-T		RASopathy	Uncertain significance (Apr 22, 2023)
15-66387389-C-G			Uncertain significance (Dec 19, 2019)
15-66387390-C-G		RASopathy • Cardiovascular phenotype	Uncertain significance (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP2K1	protein_coding	protein_coding	ENST00000307102	11	105496

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.897	0.103	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.11	88	217	0.406	0.0000121	2593
Missense in Polyphen		13	71.987	0.18059		926
Synonymous	-0.650	93	85.4	1.09	0.00000559	753
Loss of Function	3.59	3	20.6	0.146	0.00000106	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator- activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779}.
• Disease: DISEASE: Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. 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. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Prion diseases - Homo sapiens (human);PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Melanoma - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Long-term depression - Homo sapiens (human);Influenza A - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Gap junction - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Pathway_PA165959425;Sorafenib Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;VEGF Signaling Pathway;Fc Epsilon Receptor I Signaling in Mast Cells;Insulin Signalling;EGF-Core;HH-Core;IL-5 Signaling Pathway;Osteopontin Signaling;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Prolactin Signaling Pathway;IL-7 Signaling Pathway;Endothelin Pathways;IL-9 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Signaling Pathways in Glioblastoma;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Interleukin-11 Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Aryl Hydrocarbon Receptor;Nifedipine Activity;JAK-STAT;Common Pathways Underlying Drug Addiction;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Bladder Cancer;IL-3 Signaling Pathway;nerve growth factor pathway (ngf);Kit receptor signaling pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;IL-6 signaling pathway;TGF-beta Signaling Pathway;BDNF-TrkB Signaling;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PDGFR-beta pathway;miRNA regulation of prostate cancer signaling pathways;Endometrial cancer;PI3K-Akt Signaling Pathway;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;MAPK Cascade;Ras Signaling;EMT transition in Colorectal Cancer;EGF-EGFR Signaling Pathway;Insulin Signaling;IL-2 Signaling Pathway;Regulation of Actin Cytoskeleton;EPO Receptor Signaling;Senescence and Autophagy in Cancer;ErbB Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Estrogen signaling pathway;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Serotonin Receptor 4-6-7 and NR3C Signaling;Toll-like Receptor Signaling Pathway;Developmental Biology;RAGE;MAP2K and MAPK activation;RAF activation;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signal Transduction;Signaling by Interleukins;inhibition of cellular proliferation by gleevec;role of erk5 in neuronal survival pathway;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;links between pyk2 and map kinases;regulation of splicing through sam68;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;aspirin blocks signaling pathway involved in platelet activation;egf signaling pathway;trefoil factors initiate mucosal healing;anthrax toxin mechanism of action;melanocyte development and pigmentation pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;il-2 receptor beta chain in t cell activation;phospholipids as signalling intermediaries;cadmium induces dna synthesis and proliferation in macrophages;ccr3 signaling in eosinophils;mcalpain and friends in cell motility;signaling pathway from g-protein families;sprouty regulation of tyrosine kinase signals;ras-independent pathway in nk cell-mediated cytotoxicity;phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway;role of -arrestins in the activation and targeting of map kinases;t cell receptor signaling pathway;bcr signaling pathway;calcium signaling by hbx of hepatitis b virus;erk1/erk2 mapk signaling pathway;role of erbb2 in signal transduction and oncology;keratinocyte differentiation;mapkinase signaling pathway;Prolactin;Cytokine Signaling in Immune system;map kinase inactivation of smrt corepressor;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;B cell receptor signaling;Toll-Like Receptors Cascades;GPCR Adenosine A2A receptor;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Interleukin-1 signaling;CD4 T cell receptor signaling-ERK cascade;igf-1 signaling pathway;HGF;Uptake and actions of bacterial toxins;TCR;Uptake and function of anthrax toxins;Infectious disease;IGF signaling;Innate Immune System;Immune System;FGF;Negative feedback regulation of MAPK pathway;Fibroblast growth factor-1;insulin Mam;IL-1 p38;roles of arrestin dependent recruitment of src kinases in gpcr signaling;IL-1 JNK;ceramide signaling pathway;GPCR signaling-G alpha s Epac and ERK;pdgf signaling pathway;TLR p38;RAF-independent MAPK1/3 activation;IL-7 signaling;GPCR signaling-G alpha s PKA and ERK;tpo signaling pathway;Integrin;fc epsilon receptor i signaling in mast cells;MAP3K8 (TPL2)-dependent MAPK1/3 activation;EGFR1;SHP2 signaling;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;tgf beta signaling pathway;Ras signaling in the CD4+ TCR pathway;role of mal in rho-mediated activation of srf;ErbB1 downstream signaling;fmlp induced chemokine gene expression in hmc-1 cells;MyD88 dependent cascade initiated on endosome;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;JAK STAT pathway and regulation;PDGF;IL2;NGF;MAP kinase cascade;EPO signaling;Class IB PI3K non-lipid kinase events;IL3;Signal transduction by L1;IL2-mediated signaling events;Gastrin;IFN-gamma pathway;L1CAM interactions;Axon guidance;TLR ECSIT MEKK1 JNK;IL6;TLR ECSIT MEKK1 p38;TLR JNK;IL-7;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;MAPK3 (ERK1) activation;Signaling by RAS mutants;VEGF;Signaling by high-kinase activity BRAF mutants;ID;Signaling by moderate kinase activity BRAF mutants;EGF;Paradoxical activation of RAF signaling by kinase inactive BRAF;ErbB2/ErbB3 signaling events;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;GMCSF-mediated signaling events;mTOR signaling pathway;Neurotrophic factor-mediated Trk receptor signaling;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Downstream signaling in naïve CD8+ T cells;Fc-epsilon receptor I signaling in mast cells;Netrin-mediated signaling events;Signaling events mediated by focal adhesion kinase;CXCR3-mediated signaling events;EPHB forward signaling;Signaling events mediated by Stem cell factor receptor (c-Kit);FOXM1 transcription factor network;Nongenotropic Androgen signaling;PDGFR-beta signaling pathway;Trk receptor signaling mediated by the MAPK pathway;Hedgehog signaling events mediated by Gli proteins;Endothelins;Signaling events mediated by VEGFR1 and VEGFR2;Ceramide signaling pathway;Cellular roles of Anthrax toxin;Interleukin-1 family signaling;CD4 T cell receptor signaling-JNK cascade;TSLP;insulin;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.849

Intolerance Scores

• loftool: 0.0532
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.941
• hipred: Y
• hipred_score: 0.825
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Map2k1
• Phenotype: digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; skeleton phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; endocrine/exocrine gland phenotype; neoplasm; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;activation of MAPK activity;protein phosphorylation;chemotaxis;cell cycle arrest;signal transduction;heart development;negative regulation of cell population proliferation;positive regulation of gene expression;negative regulation of gene expression;peptidyl-threonine phosphorylation;peptidyl-tyrosine phosphorylation;cerebellar cortex formation;signal transduction by protein phosphorylation;neuron differentiation;keratinocyte differentiation;thyroid gland development;stress-activated protein kinase signaling cascade;activation of protein kinase activity;regulation of stress-activated MAPK cascade;positive regulation of transcription, DNA-templated;thymus development;regulation of axon regeneration;cell motility;positive regulation of axonogenesis;Bergmann glial cell differentiation;face development;trachea formation;epithelial cell proliferation involved in lung morphogenesis;placenta blood vessel development;labyrinthine layer development;ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;positive regulation of protein serine/threonine kinase activity;regulation of Golgi inheritance;cellular senescence;positive regulation of production of miRNAs involved in gene silencing by miRNA;regulation of early endosome to late endosome transport
• Cellular component: nucleus;cytoplasm;mitochondrion;early endosome;late endosome;endoplasmic reticulum;Golgi apparatus;microtubule organizing center;cytosol;plasma membrane;focal adhesion
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;protein C-terminus binding;protein serine/threonine kinase activator activity;protein N-terminus binding;scaffold protein binding