MAPK8
mitogen-activated protein kinase 8, the group of Mitogen-activated protein kinases
Basic information
Region (hg38): 10:48306638-48439360
Previous symbols: [ "PRKM8" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (19 variants)
- not specified (6 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK8 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 | 3 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 18 | 18 | ||||
| Total | 0 | 0 | 0 | 1 | 20 |
Variants in MAPK8
This is a list of pathogenic ClinVar variants found in the MAPK8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-48401535-C-A | not specified | Benign (Jan 24, 2024) | ||
| 10-48401708-A-G | MAPK8-related disorder | Likely benign (Jun 27, 2019) | ||
| 10-48401765-A-G | Likely benign (Jul 18, 2018) | |||
| 10-48404801-A-C | not specified | Benign (Jan 24, 2024) | ||
| 10-48405106-GAT-G | Benign (May 25, 2021) | |||
| 10-48405106-G-GAT | Benign (May 13, 2021) | |||
| 10-48405106-G-GATAT | Benign (May 18, 2021) | |||
| 10-48405106-G-GATATAT | Benign (May 20, 2021) | |||
| 10-48405121-A-ATG | Benign (May 13, 2021) | |||
| 10-48409799-T-A | not specified | Benign (Jan 24, 2024) | ||
| 10-48409917-C-T | Benign (Dec 31, 2019) | |||
| 10-48409974-A-G | not specified | Benign (Jan 24, 2024) | ||
| 10-48410309-T-G | Benign (May 13, 2021) | |||
| 10-48420214-C-T | MAPK8-related disorder | Likely benign (Apr 01, 2020) | ||
| 10-48425830-T-TAC | Benign (May 13, 2021) | |||
| 10-48425832-T-A | Benign (May 26, 2021) | |||
| 10-48425834-A-AATACATT | Benign (May 13, 2021) | |||
| 10-48425836-T-TTGTAAATG | Benign (May 13, 2021) | |||
| 10-48426136-G-A | not specified | Benign (Jan 24, 2024) | ||
| 10-48427029-T-A | Benign (May 22, 2021) | |||
| 10-48427234-T-G | not specified | Benign (Jan 24, 2024) | ||
| 10-48434924-G-A | Benign (Dec 31, 2019) | |||
| 10-48435183-A-G | Benign (May 13, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPK8 | protein_coding | protein_coding | ENST00000374189 | 11 | 132706 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00177 | 125650 | 0 | 2 | 125652 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.88 | 106 | 228 | 0.464 | 0.0000116 | 2814 |
| Missense in Polyphen | 11 | 75.608 | 0.14549 | 991 | ||
| Synonymous | 0.530 | 71 | 76.9 | 0.923 | 0.00000398 | 781 |
| Loss of Function | 4.24 | 1 | 22.9 | 0.0437 | 0.00000114 | 297 |
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) | 0.0000178 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). {ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:22441692}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Adipocytokine 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);Retrograde endocannabinoid signaling - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Tight junction - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);cAMP 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);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Herpes simplex infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - 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;JAK-STAT-Core;Osteoclast Signaling;Regulation of toll-like receptor signaling pathway;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Type II diabetes mellitus;Apoptosis Modulation and Signaling;IL-1 signaling pathway;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Leptin signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;AGE-RAGE pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Nanoparticle triggered regulated necrosis;JAK-STAT;EBV LMP1 signaling;Cardiac Hypertrophic Response;IL-3 Signaling Pathway;NLR Proteins;nerve growth factor pathway (ngf);Transcriptional activation by NRF2;Kit receptor signaling pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Rac1-Pak1-p38-MMP-2 pathway;Transcription factor regulation in adipogenesis;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Wnt Signaling Pathway;Hepatitis C and Hepatocellular Carcinoma;TGF-beta Signaling Pathway;Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;RIG-I-like Receptor Signaling;Canonical and Non-Canonical TGF-B signaling;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;PDGFR-beta pathway;Protein alkylation leading to liver fibrosis;Wnt Signaling in Kidney Disease;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;ErbB Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Developmental Biology;RAGE;TWEAK;Toll Like Receptor 7/8 (TLR7/8) Cascade;DNA Repair;Interleukin-17 signaling;Signal Transduction;DNA Double-Strand Break Repair;Signaling by Interleukins;DSCAM interactions;hypoxia and p53 in the cardiovascular system;inhibition of cellular proliferation by gleevec;bioactive peptide induced signaling pathway;links between pyk2 and map kinases;il12 and stat4 dependent signaling pathway in th1 development;egf signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;integrin signaling pathway;regulation of map kinase pathways through dual specificity phosphatases;hiv-1 nef: negative effector of fas and tnf;signal transduction through il1r;tnf/stress related signaling;nfat and hypertrophy of the heart ;t cell receptor signaling pathway;bcr signaling pathway;keratinocyte differentiation;toll-like receptor pathway;mapkinase signaling pathway;Prolactin;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;Fas;IL12 signaling mediated by STAT4;Cellular responses to stress;igf-1 signaling pathway;Activation of BIM and translocation to mitochondria ;Activation of BMF and translocation to mitochondria;Activation of BH3-only proteins;FCERI mediated MAPK activation;Fc epsilon receptor (FCERI) signaling;Intrinsic Pathway for Apoptosis;TCR;Innate Immune System;Immune System;Apoptosis;Programmed Cell Death;KitReceptor;ATF-2 transcription factor network;Fibroblast growth factor-1;BCR;fas signaling pathway (cd95);IL-1 p38;CRH;IL-1 JNK;TGF-beta super family signaling pathway canonical;ceramide signaling pathway;pdgf signaling pathway;IL1;Cellular responses to external stimuli;IL-7 signaling;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;atm signaling pathway;TGF_beta_Receptor;fc epsilon receptor i signaling in mast cells;BDNF;EGFR1;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;agrin in postsynaptic differentiation;Glucocorticoid receptor regulatory network;role of mal in rho-mediated activation of srf;NRIF signals cell death from the nucleus;ErbB1 downstream signaling;MyD88 dependent cascade initiated on endosome;NRAGE signals death through JNK;BCR signaling pathway;bone remodeling;JAK STAT pathway and regulation;PDGF;IL2;Noncanonical Wnt signaling pathway;EPO signaling;Netrin-1 signaling;Death Receptor Signalling;Signaling events regulated by Ret tyrosine kinase;p75 NTR receptor-mediated signalling;IL2-mediated signaling events;Gastrin;Ephrin B reverse signaling;Angiopoietin receptor Tie2-mediated signaling;Rapid glucocorticoid signaling;IL4;EPO signaling pathway;Axon guidance;Leptin;TGF-beta signaling TAK1;TLR ECSIT MEKK1 JNK;IL6;Wnt;TNFalpha;TLR JNK;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;EGF;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;Osteopontin-mediated events;Glypican 3 network;HIV-1 Nef: Negative effector of Fas and TNF-alpha;RAC1 signaling pathway;CD40/CD40L signaling;TRAIL signaling pathway;CDC42 signaling events;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;N-cadherin signaling events;Signaling events mediated by focal adhesion kinase;Retinoic acid receptors-mediated signaling;Reelin signaling pathway;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;Regulation of Androgen receptor activity;Signaling events mediated by Stem cell factor receptor (c-Kit);FAS (CD95) signaling pathway;JNK signaling in the CD4+ TCR pathway;FoxO family signaling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;PDGFR-beta signaling pathway;IL1-mediated signaling events;Endothelins;Nephrin/Neph1 signaling in the kidney podocyte;Ceramide signaling pathway;p53 pathway;Syndecan-2-mediated signaling events;RhoA signaling pathway;S1P2 pathway;CD4 T cell receptor signaling-JNK cascade;TSLP;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.995
Intolerance Scores
- loftool
- 0.126
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.07
Haploinsufficiency Scores
- pHI
- 0.957
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.654
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
- Mapk8
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; 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; 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); reproductive system phenotype; vision/eye 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); renal/urinary system phenotype;
Zebrafish Information Network
- Gene name
- mapk8b
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- wholly ventralized
Gene ontology
- Biological process
- protein phosphorylation;JNK cascade;JUN phosphorylation;response to UV;response to mechanical stimulus;regulation of gene expression;positive regulation of gene expression;regulation of macroautophagy;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;regulation of histone deacetylation;positive regulation of cyclase activity;negative regulation of protein binding;regulation of protein localization;cellular response to amino acid starvation;cellular response to reactive oxygen species;intracellular signal transduction;Fc-epsilon receptor signaling pathway;regulation of circadian rhythm;positive regulation of apoptotic process;negative regulation of apoptotic process;rhythmic process;neuron development;positive regulation of protein metabolic process;stress-activated MAPK cascade;cellular response to lipopolysaccharide;cellular response to mechanical stimulus;cellular response to cadmium ion;cellular response to organic substance;cellular response to cytokine stimulus;positive regulation of deacetylase activity;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;regulation of DNA replication origin binding
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;axon;neuron projection;basal dendrite
- Molecular function
- protein serine/threonine kinase activity;JUN kinase activity;MAP kinase activity;protein binding;ATP binding;kinase activity;enzyme binding;histone deacetylase regulator activity;histone deacetylase binding