MAPKAPK2
MAPK activated protein kinase 2, the group of MAPK activated protein kinases
Basic information
Region (hg38): 1:206684905-206734281
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 MAPKAPK2 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 | 4 | |||||
| missense | 23 | 24 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 24 | 4 | 1 |
Variants in MAPKAPK2
This is a list of pathogenic ClinVar variants found in the MAPKAPK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-206685280-G-C | Likely benign (Dec 20, 2017) | |||
| 1-206685292-G-C | Likely benign (Dec 20, 2017) | |||
| 1-206685294-A-C | not specified | Uncertain significance (Sep 30, 2024) | ||
| 1-206685295-G-C | not specified | Uncertain significance (Sep 30, 2024) | ||
| 1-206685320-C-A | not specified | Uncertain significance (Sep 25, 2023) | ||
| 1-206685323-C-G | not specified | Uncertain significance (Aug 11, 2024) | ||
| 1-206685327-C-G | not specified | Uncertain significance (Jan 31, 2024) | ||
| 1-206685427-C-T | Benign (Dec 04, 2017) | |||
| 1-206685432-A-G | not specified | Uncertain significance (Dec 04, 2024) | ||
| 1-206685493-G-T | not specified | Uncertain significance (Sep 18, 2024) | ||
| 1-206728758-C-T | not specified | Uncertain significance (Mar 02, 2023) | ||
| 1-206728762-C-T | not specified | Uncertain significance (Jan 30, 2024) | ||
| 1-206729060-C-T | Neurodevelopmental disorder | Uncertain significance (Jan 01, 2019) | ||
| 1-206729070-A-G | not specified | Uncertain significance (Jun 18, 2021) | ||
| 1-206729990-A-G | not specified | Uncertain significance (Mar 08, 2024) | ||
| 1-206730012-T-C | not specified | Uncertain significance (Oct 03, 2022) | ||
| 1-206730023-A-G | not specified | Uncertain significance (Jul 26, 2022) | ||
| 1-206730750-A-G | not specified | Uncertain significance (Apr 28, 2023) | ||
| 1-206731167-A-G | not specified | Uncertain significance (Aug 10, 2021) | ||
| 1-206731171-C-T | Likely benign (Dec 04, 2017) | |||
| 1-206731181-A-G | not specified | Uncertain significance (Oct 04, 2024) | ||
| 1-206731209-G-A | not specified | Uncertain significance (Feb 23, 2023) | ||
| 1-206731233-A-G | not specified | Uncertain significance (Jul 14, 2021) | ||
| 1-206731679-C-A | not specified | Uncertain significance (Dec 18, 2023) | ||
| 1-206731705-A-T | not specified | Uncertain significance (May 27, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPKAPK2 | protein_coding | protein_coding | ENST00000367103 | 10 | 49340 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000428 | 125742 | 0 | 5 | 125747 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.05 | 98 | 227 | 0.431 | 0.0000131 | 2596 |
| Missense in Polyphen | 16 | 74.592 | 0.2145 | 787 | ||
| Synonymous | -0.635 | 98 | 90.3 | 1.09 | 0.00000527 | 767 |
| Loss of Function | 4.37 | 0 | 22.3 | 0.00 | 0.00000120 | 250 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000578 | 0.0000578 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000188 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.;
- Pathway
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);EGF-Core;IL-1 signaling pathway;Regulation of Microtubule Cytoskeleton;Structural Pathway of Interleukin 1 (IL-1);Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;p38 MAPK Signaling Pathway;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Serotonin Receptor 4-6-7 and NR3C Signaling;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;p38 mapk signaling pathway;VEGFA-VEGFR2 Pathway;stress induction of hsp regulation;Regulation of HSF1-mediated heat shock response;Metabolism of lipids;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;Synthesis of Leukotrienes (LT) and Eoxins (EX);Cellular responses to stress;Arachidonic acid metabolism;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA;Metabolism of RNA;Innate Immune System;Immune System;Metabolism;Fibroblast growth factor-1;Fatty acid metabolism;Nuclear Events (kinase and transcription factor activation);BCR;p38MAPK events;Signalling to RAS;Cellular responses to external stimuli;IL-7 signaling;Signalling to ERKs;Signaling by NTRK1 (TRKA);activated TAK1 mediates p38 MAPK activation;CREB phosphorylation;Signaling by NTRKs;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;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;Cellular response to heat stress;EPO signaling;IL2-mediated signaling events;Signaling by VEGF;TNFalpha;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;p38 signaling mediated by MAPKAP kinases;Trk receptor signaling mediated by the MAPK pathway;Signaling events mediated by VEGFR1 and VEGFR2
(Consensus)
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- loftool
- 0.202
- rvis_EVS
- -0.65
- rvis_percentile_EVS
- 16.36
Haploinsufficiency Scores
- pHI
- 0.433
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.455
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Mapkapk2
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; vision/eye 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); normal 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); neoplasm; immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail 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);
Zebrafish Information Network
- Gene name
- mapkapk2a
- Affected structure
- I-YSL
- Phenotype tag
- abnormal
- Phenotype quality
- aggregated
Gene ontology
- Biological process
- MAPK cascade;activation of MAPK activity;toll-like receptor signaling pathway;protein phosphorylation;leukotriene metabolic process;inflammatory response;cellular response to DNA damage stimulus;peptidyl-serine phosphorylation;response to lipopolysaccharide;regulation of interleukin-6 production;regulation of tumor necrosis factor production;response to cytokine;intracellular signal transduction;cellular response to vascular endothelial growth factor stimulus;p38MAPK cascade;positive regulation of tumor necrosis factor biosynthetic process;regulation of mRNA stability;macropinocytosis;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;inner ear development;3'-UTR-mediated mRNA stabilization;regulation of cellular response to heat
- Cellular component
- nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;extracellular exosome
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;protein binding;calmodulin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity;mitogen-activated protein kinase binding