MAP2K3

mitogen-activated protein kinase kinase 3, the group of Mitogen-activated protein kinase kinases

Basic information

Region (hg38): 17:21284671-21315232

Previous symbols: [ "PRKMK3" ]

Links

ENSG00000034152 ∙ NCBI:5606 ∙ OMIM:602315 ∙ HGNC:6843 ∙ Uniprot:P46734 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP2K3 gene.

• not provided (35 variants)
• Inborn genetic diseases (4 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K3 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				10	6	16
missense			6	5	10	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					2	2
Total	0	0	6	15	18

Variants in MAP2K3

This is a list of pathogenic ClinVar variants found in the MAP2K3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-21298407-T-C			Benign (Jun 04, 2018)
17-21298438-A-C			Benign (Dec 31, 2019)
17-21298479-C-T			Likely benign (Feb 01, 2018)
17-21298879-C-A			Benign (Jun 04, 2018)
17-21298916-T-C			Benign (Jun 26, 2018)
17-21298925-G-C			Benign (Jun 04, 2018)
17-21300581-T-C			Benign (Jun 04, 2018)
17-21300595-T-C			Likely benign (Dec 31, 2019)
17-21300622-G-A			Likely benign (Jun 04, 2018)
17-21300629-G-A			Benign (Dec 31, 2019)
17-21300634-G-C		not specified	Uncertain significance (Mar 01, 2023)
17-21300637-C-T			Likely benign (Jun 04, 2018)
17-21300649-G-A			Benign (Dec 31, 2019)
17-21300880-C-T		Hepatocellular carcinoma	Pathogenic (Jun 15, 2021)
17-21302148-C-T			Likely benign (Jun 04, 2018)
17-21302216-A-G		not specified	Uncertain significance (Jun 12, 2023)
17-21302241-T-C			Benign (Dec 31, 2019)
17-21302249-T-C			Likely benign (Dec 31, 2019)
17-21303244-C-T			Benign (Jun 04, 2018)
17-21304480-A-T			Likely benign (Jun 14, 2018)
17-21304484-T-C			Benign (Jul 13, 2018)
17-21304501-T-G		not specified	Uncertain significance (Mar 25, 2015)
17-21304517-C-T			Benign (Dec 31, 2019)
17-21304522-C-T			Benign (Dec 31, 2019)
17-21304526-G-C			Likely benign (Nov 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP2K3	protein_coding	protein_coding	ENST00000342679	12	30569

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0220	0.975	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.80	111	179	0.620	0.00000974	2108
Missense in Polyphen		28	62.576	0.44746		759
Synonymous	1.31	53	66.6	0.796	0.00000393	557
Loss of Function	2.60	6	17.9	0.336	8.58e-7	218

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.000219	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000219	0.000217
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}.
• Disease: DISEASE: Note=Defects in MAP2K3 may be involved in colon cancer.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;VEGF Signaling Pathway;Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Core;Regulation of toll-like receptor signaling pathway;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;Integrin-mediated Cell Adhesion;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling Pathways in Glioblastoma;TNF alpha Signaling Pathway;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Endoderm Differentiation;Photodynamic therapy-induced AP-1 survival signaling.;TGF-beta Signaling Pathway;MAPK Signaling Pathway;4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;ESC Pluripotency Pathways;MAPK Cascade;EMT transition in Colorectal Cancer;Insulin Signaling;Interferon type I signaling pathways;Senescence and Autophagy in Cancer;Serotonin HTR1 Group and FOS Pathway;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signaling by Interleukins;links between pyk2 and map kinases;gata3 participate in activating the th2 cytokine genes expression;human cytomegalovirus and map kinase pathways;signal transduction through il1r;tnf/stress related signaling;the 41bb-dependent immune response;nfkb activation by nontypeable hemophilus influenzae;keratinocyte differentiation;toll-like receptor pathway;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;Oxidative Stress Induced Senescence;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Cellular Senescence;Cellular responses to stress;Uptake and actions of bacterial toxins;Uptake and function of anthrax toxins;Infectious disease;Innate Immune System;Immune System;BMP2 signaling TAK1;IL-1 p38;IL-1 JNK;IL1;TLR p38;Cellular responses to external stimuli;IL-7 signaling;TGF_beta_Receptor;activated TAK1 mediates p38 MAPK activation;EGFR1;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;fmlp induced chemokine gene expression in hmc-1 cells;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;EPO signaling;TGF-beta signaling TAK1;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TSH;TLR JNK;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;VEGF;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;RAC1 signaling pathway;TNF receptor signaling pathway ;CDC42 signaling events;Regulation of p38-alpha and p38-beta;CXCR3-mediated signaling events;p38 MAPK signaling pathway;Trk receptor signaling mediated by the MAPK pathway;Signaling events mediated by VEGFR1 and VEGFR2;IL12-mediated signaling events;Signaling mediated by p38-gamma and p38-delta;RhoA signaling pathway;Cellular roles of Anthrax toxin (Consensus)

Recessive Scores

• pRec: 0.340

Intolerance Scores

• loftool: 0.736
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.91

Haploinsufficiency Scores

• pHI: 0.235
• hipred: Y
• hipred_score: 0.669
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map2k3
• Phenotype: cellular phenotype; immune system phenotype; hematopoietic system phenotype; 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)

Gene ontology

• Biological process: activation of MAPK activity;inflammatory response;signal transduction;peptidyl-tyrosine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;cellular response to vascular endothelial growth factor stimulus;p38MAPK cascade;regulation of cytokine biosynthetic process;positive regulation of blood vessel endothelial cell migration;positive regulation of protein kinase activity;positive regulation of transcription, DNA-templated;cardiac muscle contraction
• Cellular component: nucleoplasm;cytoplasm;cytosol;membrane
• Molecular function: protein serine/threonine kinase activity;MAP kinase kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;protein kinase binding