MAP2K6
mitogen-activated protein kinase kinase 6, the group of Mitogen-activated protein kinase kinases
Basic information
Region (hg38): 17:69414697-69553865
Previous symbols: [ "PRKMK6" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K6 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 | 0 | |||||
| missense | 7 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 7 | 0 | 0 |
Variants in MAP2K6
This is a list of pathogenic ClinVar variants found in the MAP2K6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-69505845-A-G | not specified | Uncertain significance (Mar 22, 2023) | ||
| 17-69517533-A-G | not specified | Uncertain significance (Feb 07, 2023) | ||
| 17-69517567-T-C | not specified | Uncertain significance (Apr 04, 2024) | ||
| 17-69520333-A-G | not specified | Uncertain significance (Dec 28, 2023) | ||
| 17-69523534-C-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 17-69523546-C-A | not specified | Uncertain significance (Mar 24, 2023) | ||
| 17-69526589-G-A | not specified | Uncertain significance (Aug 13, 2021) | ||
| 17-69526648-C-T | not specified | Uncertain significance (May 18, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAP2K6 | protein_coding | protein_coding | ENST00000590474 | 12 | 128634 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.913 | 0.0867 | 125738 | 0 | 6 | 125744 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.01 | 71 | 187 | 0.380 | 0.00000984 | 2193 |
| Missense in Polyphen | 10 | 65.674 | 0.15227 | 741 | ||
| Synonymous | 0.546 | 61 | 66.7 | 0.915 | 0.00000361 | 621 |
| Loss of Function | 3.94 | 4 | 25.5 | 0.157 | 0.00000157 | 258 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000294 | 0.0000294 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000265 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG- dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11727828, ECO:0000269|PubMed:15550393, ECO:0000269|PubMed:20869211, ECO:0000269|PubMed:8622669, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9218798}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - 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);Toll-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;VEGF Signaling Pathway;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Core;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;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;Amyotrophic lateral sclerosis (ALS);Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;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;p38 MAPK Signaling Pathway;MAPK Cascade;EMT transition in Colorectal Cancer;Insulin Signaling;Interferon type I signaling pathways;Serotonin HTR1 Group and FOS Pathway;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Gene expression (Transcription);Signaling by Interleukins;il12 and stat4 dependent signaling pathway in th1 development;gata3 participate in activating the th2 cytokine genes expression;human cytomegalovirus and map kinase pathways;p38 mapk signaling pathway;il-10 anti-inflammatory signaling pathway;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;Generic Transcription 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;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Cellular responses to stress;Interleukin-1 signaling;RNA Polymerase II Transcription;PI5P Regulates TP53 Acetylation;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;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;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;TGF-beta signaling TAK1;TLR ECSIT MEKK1 JNK;IL6;TLR ECSIT MEKK1 p38;TSH;TNFalpha;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;CDC42 signaling events;Regulation of p38-alpha and p38-beta;CXCR3-mediated signaling events;p38 MAPK signaling pathway;Regulation of Androgen receptor activity;FAS (CD95) signaling pathway;IL1-mediated signaling events;Trk receptor signaling mediated by the MAPK pathway;IL6-mediated signaling events;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;Interleukin-1 family signaling
(Consensus)
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- loftool
- 0.366
- rvis_EVS
- -0.32
- rvis_percentile_EVS
- 31.46
Haploinsufficiency Scores
- pHI
- 0.823
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.597
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- 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
- Map2k6
- Phenotype
- endocrine/exocrine gland phenotype; immune system phenotype; cellular phenotype; hematopoietic system phenotype;
Gene ontology
- Biological process
- MAPK cascade;activation of MAPK activity;response to ischemia;apoptotic process;DNA damage induced protein phosphorylation;cell cycle arrest;signal transduction;peptidyl-tyrosine phosphorylation;ovulation cycle process;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of prostaglandin secretion;response to drug;positive regulation of apoptotic process;positive regulation of nitric-oxide synthase biosynthetic process;cardiac muscle contraction;nucleotide-binding oligomerization domain containing signaling pathway;cellular response to sorbitol;negative regulation of cold-induced thermogenesis
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;cytoskeleton
- Molecular function
- protein serine/threonine kinase activity;MAP kinase kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;protein kinase binding