MAP2K4
mitogen-activated protein kinase kinase 4, the group of Mitogen-activated protein kinase kinases|MicroRNA protein coding host genes
Basic information
Region (hg38): 17:12020828-12143830
Previous symbols: [ "SERK1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (12 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K4 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 | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 12 | 0 | 0 |
Variants in MAP2K4
This is a list of pathogenic ClinVar variants found in the MAP2K4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-12020900-G-T | not specified | Uncertain significance (Jul 14, 2021) | ||
| 17-12020902-C-G | not specified | Uncertain significance (Dec 02, 2022) | ||
| 17-12020911-G-A | not specified | Uncertain significance (Apr 07, 2022) | ||
| 17-12020911-G-C | not specified | Uncertain significance (Dec 01, 2022) | ||
| 17-12020929-G-A | not specified | Uncertain significance (Jun 12, 2023) | ||
| 17-12020945-C-T | not specified | Uncertain significance (Dec 02, 2022) | ||
| 17-12020953-C-A | not specified | Uncertain significance (Jan 30, 2024) | ||
| 17-12020956-G-A | not specified | Uncertain significance (Dec 28, 2022) | ||
| 17-12054961-C-A | not specified | Uncertain significance (Oct 13, 2023) | ||
| 17-12081402-A-C | not specified | Uncertain significance (Aug 04, 2023) | ||
| 17-12081494-G-T | not specified | Uncertain significance (Jul 14, 2021) | ||
| 17-12107814-C-G | Neuroblastoma | other (May 01, 2016) | ||
| 17-12107848-A-G | not specified | Uncertain significance (Jun 01, 2023) | ||
| 17-12125348-G-A | not specified | Uncertain significance (Aug 09, 2021) | ||
| 17-12141146-G-C | not provided (-) | |||
| 17-12141201-G-A | not specified | Uncertain significance (Mar 03, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAP2K4 | protein_coding | protein_coding | ENST00000353533 | 11 | 123007 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00291 | 125721 | 0 | 1 | 125722 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.23 | 71 | 199 | 0.356 | 0.0000103 | 2634 |
| Missense in Polyphen | 21 | 94.694 | 0.22177 | 1186 | ||
| Synonymous | 0.0871 | 68 | 68.9 | 0.987 | 0.00000365 | 741 |
| Loss of Function | 4.10 | 1 | 21.6 | 0.0464 | 0.00000119 | 268 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| 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. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}.;
- Pathway
- Relaxin signaling pathway - 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);ErbB signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Hepatitis B - 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;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;Angiogenesis overview;Signaling Pathways in Glioblastoma;TNF alpha Signaling Pathway;PDGF Pathway;Apoptosis;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Photodynamic therapy-induced AP-1 survival signaling.;Apoptotic Signaling Pathway;IL-6 signaling pathway;TGF-beta Signaling Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Oxidative Damage;PDGFR-beta pathway;Wnt Signaling Pathway and Pluripotency;p38 MAPK Signaling Pathway;MAPK Cascade;EMT transition in Colorectal Cancer;Insulin Signaling;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signaling by Interleukins;inhibition of cellular proliferation by gleevec;links between pyk2 and map kinases;tnfr1 signaling pathway;egf signaling pathway;p38 mapk signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;tnf/stress related signaling;t cell receptor signaling pathway;keratinocyte differentiation;toll-like receptor pathway;mapkinase signaling pathway;Cytokine Signaling in Immune system;map kinase inactivation of smrt corepressor;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;Fas;Cellular responses to stress;Interleukin-1 signaling;FCERI mediated MAPK activation;Uptake and actions of bacterial toxins;Fc epsilon receptor (FCERI) signaling;Uptake and function of anthrax toxins;Infectious disease;Innate Immune System;Immune System;fas signaling pathway (cd95);IL-1 p38;IL-1 JNK;ceramide signaling pathway;pdgf signaling pathway;IL1;TLR p38;Cellular responses to external stimuli;IL-7 signaling;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;fc epsilon receptor i signaling in mast cells;MAP3K8 (TPL2)-dependent MAPK1/3 activation;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;ErbB1 downstream signaling;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;PDGF;VEGFR3 signaling in lymphatic endothelium;EPO signaling;Ephrin B reverse signaling;TGF-beta signaling TAK1;TLR ECSIT MEKK1 JNK;IL6;TLR ECSIT MEKK1 p38;TLR JNK;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF;EGF;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;CD40/CD40L signaling;TRAIL signaling pathway;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Signaling events mediated by focal adhesion kinase;Regulation of p38-alpha and p38-beta;Regulation of Androgen receptor activity;JNK signaling in the CD4+ TCR pathway;PDGFR-beta signaling pathway;IL6-mediated signaling events;Nephrin/Neph1 signaling in the kidney podocyte;Ceramide signaling pathway;RhoA signaling pathway;Cellular roles of Anthrax toxin;Interleukin-1 family signaling
(Consensus)
Recessive Scores
- pRec
- 0.661
Intolerance Scores
- loftool
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 33.97
Haploinsufficiency Scores
- pHI
- 0.454
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.665
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- 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
- Map2k4
- 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); 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); normal 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); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; 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); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- map2k4b
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- activation of MAPK activity;apoptotic process;signal transduction;JNK cascade;activation of JUN kinase activity;response to wounding;peptidyl-tyrosine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of smooth muscle cell apoptotic process;positive regulation of neuron apoptotic process;positive regulation of DNA replication;positive regulation of nitric-oxide synthase biosynthetic process;cell growth involved in cardiac muscle cell development;cellular response to mechanical stimulus;cellular response to sorbitol;negative regulation of motor neuron apoptotic process
- Cellular component
- nucleus;cytoplasm;cytosol;axon;dendrite cytoplasm;perikaryon
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;JUN kinase kinase activity;mitogen-activated protein kinase kinase kinase binding