MAPK12
mitogen-activated protein kinase 12, the group of Mitogen-activated protein kinases
Basic information
Region (hg38): 22:50245450-50261716
Previous symbols: [ "SAPK3" ]
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 MAPK12 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 | 27 | 29 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 28 | 2 | 0 |
Variants in MAPK12
This is a list of pathogenic ClinVar variants found in the MAPK12 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 22-50245530-A-G | not specified | Uncertain significance (Dec 12, 2022) | ||
| 22-50245698-C-G | not specified | Uncertain significance (Apr 08, 2023) | ||
| 22-50245951-G-A | not specified | Uncertain significance (Feb 17, 2023) | ||
| 22-50245969-G-A | not specified | Uncertain significance (Dec 21, 2023) | ||
| 22-50245995-T-C | not specified | Uncertain significance (Dec 14, 2022) | ||
| 22-50246017-G-C | not specified | Uncertain significance (Dec 13, 2022) | ||
| 22-50246309-G-C | not specified | Uncertain significance (Apr 18, 2023) | ||
| 22-50246336-C-G | not specified | Uncertain significance (Aug 21, 2023) | ||
| 22-50246343-C-G | not specified | Uncertain significance (Aug 17, 2021) | ||
| 22-50246351-C-T | not specified | Uncertain significance (Jun 06, 2023) | ||
| 22-50246372-T-G | not specified | Uncertain significance (May 16, 2023) | ||
| 22-50246373-C-A | not specified | Uncertain significance (May 16, 2023) | ||
| 22-50246704-G-A | not specified | Uncertain significance (Feb 22, 2023) | ||
| 22-50246709-A-G | not specified | Uncertain significance (Dec 30, 2023) | ||
| 22-50246923-G-T | not specified | Uncertain significance (Dec 17, 2023) | ||
| 22-50246927-C-T | not specified | Uncertain significance (Dec 07, 2021) | ||
| 22-50247706-T-C | not specified | Uncertain significance (Mar 19, 2024) | ||
| 22-50247730-T-C | not specified | Uncertain significance (Feb 05, 2024) | ||
| 22-50247938-A-G | not specified | Uncertain significance (Sep 26, 2023) | ||
| 22-50247962-G-T | not specified | Uncertain significance (Aug 21, 2023) | ||
| 22-50247971-G-C | not specified | Uncertain significance (Jul 11, 2023) | ||
| 22-50247995-C-A | not specified | Uncertain significance (Sep 30, 2021) | ||
| 22-50248008-C-T | not specified | Likely benign (Jun 04, 2024) | ||
| 22-50248074-C-G | not specified | Uncertain significance (Mar 01, 2024) | ||
| 22-50248080-G-T | not specified | Uncertain significance (Aug 15, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPK12 | protein_coding | protein_coding | ENST00000215659 | 12 | 16376 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.87e-7 | 0.882 | 125265 | 1 | 329 | 125595 | 0.00131 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.466 | 234 | 215 | 1.09 | 0.0000136 | 2358 |
| Missense in Polyphen | 105 | 94.476 | 1.1114 | 1014 | ||
| Synonymous | -1.60 | 115 | 95.2 | 1.21 | 0.00000686 | 694 |
| Loss of Function | 1.59 | 13 | 20.8 | 0.624 | 0.00000110 | 238 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00564 | 0.00563 |
| Ashkenazi Jewish | 0.00171 | 0.00169 |
| East Asian | 0.000435 | 0.000435 |
| Finnish | 0.00257 | 0.00254 |
| European (Non-Finnish) | 0.000418 | 0.000414 |
| Middle Eastern | 0.000435 | 0.000435 |
| South Asian | 0.000359 | 0.000359 |
| Other | 0.000660 | 0.000653 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 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 such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma- radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}.;
- Disease
- DISEASE: Note=MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.;
- 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);Oocyte meiosis - 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;EGF-Core;Regulation of toll-like receptor signaling pathway;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Integrin-mediated Cell Adhesion;Parkinsons Disease Pathway;Signal Transduction of S1P Receptor;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;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;ESC Pluripotency Pathways;Protein alkylation leading to liver fibrosis;MAPK Cascade;EMT transition in Colorectal Cancer;Insulin Signaling;Toll-like Receptor Signaling Pathway;Developmental Biology;mapkinase signaling pathway;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Innate Immune System;Immune System;KitReceptor;BMP2 signaling TAK1;IL-1 p38;TGF-beta super family signaling pathway canonical;TLR p38;CDO in myogenesis;Myogenesis;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;TGF-beta signaling TAK1;Mitochondrial biogenesis;TLR ECSIT MEKK1 p38;VEGF;Signaling mediated by p38-gamma and p38-delta;RhoA signaling pathway;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.437
Intolerance Scores
- loftool
- 0.778
- rvis_EVS
- -0.35
- rvis_percentile_EVS
- 29.43
Haploinsufficiency Scores
- pHI
- 0.459
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.611
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mapk12
- Phenotype
- cellular phenotype; 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);
Gene ontology
- Biological process
- MAPK cascade;DNA damage induced protein phosphorylation;cell cycle arrest;signal transduction;muscle organ development;regulation of gene expression;positive regulation of peptidase activity;peptidyl-serine phosphorylation;intracellular signal transduction;myoblast differentiation;positive regulation of muscle cell differentiation;cellular response to organic substance
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol
- Molecular function
- magnesium ion binding;protein serine/threonine kinase activity;MAP kinase activity;protein binding;ATP binding