MAPK11
mitogen-activated protein kinase 11, the group of Mitogen-activated protein kinases
Basic information
Region (hg38): 22:50263713-50270767
Previous symbols: [ "PRKM11" ]
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 MAPK11 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 | 1 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 1 | 0 |
Variants in MAPK11
This is a list of pathogenic ClinVar variants found in the MAPK11 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 22-50264983-G-C | not specified | Uncertain significance (Feb 14, 2024) | ||
| 22-50264995-G-A | not specified | Uncertain significance (May 27, 2022) | ||
| 22-50265328-C-G | not specified | Uncertain significance (Dec 19, 2022) | ||
| 22-50265341-C-T | not specified | Uncertain significance (Mar 24, 2023) | ||
| 22-50265361-C-G | not specified | Uncertain significance (Mar 21, 2023) | ||
| 22-50265396-G-A | not specified | Uncertain significance (Jul 13, 2022) | ||
| 22-50265426-C-A | not specified | Uncertain significance (Mar 20, 2024) | ||
| 22-50265454-G-A | Likely benign (Nov 01, 2022) | |||
| 22-50265630-T-G | not specified | Uncertain significance (Sep 17, 2021) | ||
| 22-50266233-G-A | not specified | Uncertain significance (Mar 06, 2023) | ||
| 22-50266551-G-C | not specified | Uncertain significance (Jan 03, 2024) | ||
| 22-50266585-T-C | not specified | Uncertain significance (Aug 23, 2021) | ||
| 22-50266618-G-A | Benign (Apr 16, 2018) | |||
| 22-50267003-C-T | not specified | Uncertain significance (Dec 15, 2023) | ||
| 22-50267141-C-T | not specified | Uncertain significance (Jan 19, 2024) | ||
| 22-50267482-C-T | not specified | Likely benign (Mar 20, 2024) | ||
| 22-50267837-G-A | not specified | Uncertain significance (Jul 26, 2021) | ||
| 22-50267933-G-A | not specified | Uncertain significance (Apr 07, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPK11 | protein_coding | protein_coding | ENST00000330651 | 12 | 7055 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000336 | 0.989 | 125428 | 0 | 9 | 125437 | 0.0000359 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.14 | 129 | 218 | 0.592 | 0.0000137 | 2322 |
| Missense in Polyphen | 50 | 107.58 | 0.46479 | 1120 | ||
| Synonymous | 1.47 | 78 | 96.4 | 0.809 | 0.00000683 | 695 |
| Loss of Function | 2.26 | 9 | 19.9 | 0.453 | 8.98e-7 | 237 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000586 | 0.0000586 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000378 | 0.0000353 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.0000329 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane- associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);VEGF Signaling Pathway;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;EGF-Core;Regulation of toll-like receptor signaling pathway;Physiological and Pathological Hypertrophy of the Heart;Angiogenesis overview;Parkinsons Disease Pathway;Structural Pathway of Interleukin 1 (IL-1);Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;MAPK Signaling Pathway;RIG-I-like Receptor Signaling;IL-4 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Protein alkylation leading to liver fibrosis;EMT transition in Colorectal Cancer;Insulin Signaling;Toll-like Receptor Signaling Pathway;Developmental Biology;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;VEGFA-VEGFR2 Pathway;nfkb activation by nontypeable hemophilus influenzae;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;KSRP (KHSRP) binds and destabilizes mRNA;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;RNA Polymerase II Transcription;Metabolism of RNA;TCR;Innate Immune System;Immune System;p73 transcription factor network;BMP2 signaling TAK1;ATF-2 transcription factor network;Nuclear Events (kinase and transcription factor activation);IL-1 p38;TGF-beta super family signaling pathway canonical;TLR p38;p38MAPK events;Signalling to RAS;Cellular responses to external stimuli;CDO in myogenesis;Myogenesis;IL-7 signaling;Signalling to ERKs;Signaling by NTRK1 (TRKA);activated TAK1 mediates p38 MAPK activation;Signaling by NTRKs;ERK/MAPK targets;Activation of the AP-1 family of transcription factors;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Glucocorticoid receptor regulatory network;MyD88 dependent cascade initiated on endosome;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;VEGFR3 signaling in lymphatic endothelium;EPO signaling;Regulation of TP53 Activity through Phosphorylation;IL2-mediated signaling events;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by VEGF;Rapid glucocorticoid signaling;IL4;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;TGF-beta signaling TAK1;Mitochondrial biogenesis;TLR ECSIT MEKK1 p38;Regulation of mRNA stability by proteins that bind AU-rich elements;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;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;Signaling mediated by p38-alpha and p38-beta;CD40/CD40L signaling;Regulation of p38-alpha and p38-beta;CXCR3-mediated signaling events;p38 MAPK signaling pathway;Plasma membrane estrogen receptor signaling;FAS (CD95) signaling pathway;p38 signaling mediated by MAPKAP kinases;Regulation of retinoblastoma protein;IL6-mediated signaling events;Signaling events mediated by VEGFR1 and VEGFR2;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.505
Intolerance Scores
- loftool
- 0.642
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 43.29
Haploinsufficiency Scores
- pHI
- 0.597
- hipred
- Y
- hipred_score
- 0.733
- ghis
- 0.623
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mapk11
- Phenotype
- muscle phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; hematopoietic system 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); reproductive 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); normal phenotype; digestive/alimentary 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); immune system phenotype;
Gene ontology
- Biological process
- activation of MAPK activity;regulation of gene expression;positive regulation of gene expression;intracellular signal transduction;positive regulation of erythrocyte differentiation;positive regulation of muscle cell differentiation;stress-activated MAPK cascade;negative regulation of cardiac muscle cell proliferation;cellular response to organic substance;cellular response to interleukin-1;cellular response to virus;regulation of signal transduction by p53 class mediator;positive regulation of interleukin-12 secretion
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- protein serine/threonine kinase activity;MAP kinase activity;protein binding;ATP binding