MAPK13
protein-codingmitogen-activated protein kinase 13, the group of Mitogen-activated protein kinases
Gene summary
This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]
- PRKM13
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAPK13 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002754.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 52 | 1 | 1 | 54 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 57 | 2 | 2 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002745.1 | 12 | MANE Select | |
| Ensembl | ENSP00000211287.4 | 12 | MANE Select | |
| Ensembl | ENSP00000362864.1 | 7 | Standard | |
| Ensembl | ENSP00000362871.5 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- response to osmotic stress
- cell cycle
- regulation of gene expression
- peptidyl-serine phosphorylation
- positive regulation of interleukin-6 production
Molecular Function
- protein serine/threonine kinase activity
- MAP kinase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000211287
- Coding exons
- 12
- Length
- 12257
- Individuals with no LoFs
- 125433
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 315
- Defined
- 125748
- p
- 0.00125
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.475 | 201 | 221 | 0.910 | 0.0000132 | 2380 |
| Missense (PolyPhen) | 85 | 97.777 | 0.86933 | 1073 | ||
| Synonymous | 0.553 | 84 | 90.7 | 0.926 | 0.00000567 | 683 |
| Loss of Function | 1.12 | 19 | 25.1 | 0.758 | 0.00000146 | 253 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00012 | rare |
| Latino/Admixed American | 0.0029 | 0.0028 | notable |
| Ashkenazi Jewish | 0.0044 | 0.0041 | notable |
| East Asian | 0.00051 | 0.00049 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.0014 | 0.0012 | notable |
| South Asian | 0.00064 | 0.00062 | rare |
| Other | 0.0018 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 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. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}.;
Recessive Scores
- pRec
- 0.0921
Intolerance Scores
- LoFtool
- 0.901
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |