MAPK4
protein-codingmitogen-activated protein kinase 4, the group of Mitogen-activated protein kinases
Gene summary
Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
- PRKM4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~171.7 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 MAPK4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002747.4. 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 | 2 | 2 | ||||
| missense | 89 | 1 | 90 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 91 | 3 | 0 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002738.2 | 5 | MANE Select | |
| Ensembl | ENSP00000383234.1 | 5 | MANE Select | |
| RefSeq | NP_001278968.1 | 4 | Standard | |
| RefSeq | NP_001278969.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- IL-17 signaling pathway - Homo sapiens (human)
- VEGF Signaling Pathway
- MicroRNAs in cardiomyocyte hypertrophy
- Integrin-mediated Cell Adhesion
- B Cell Receptor Signaling Pathway
Biological Process
- MAPK cascade
- protein phosphorylation
- cell cycle
- regulation of gene expression
- intracellular signal transduction
Molecular Function
- protein serine/threonine kinase activity
- MAP kinase activity
- protein binding
- ATP binding
- protein kinase binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400384
- Coding exons
- 5
- Length
- 171747
- Individuals with no LoFs
- 124899
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124909
- p
- 0.0000400
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.68 | 282 | 373 | 0.756 | 0.0000271 | 3798 |
| Missense (PolyPhen) | 110 | 175.12 | 0.62814 | 1858 | ||
| Synonymous | 0.0896 | 173 | 175 | 0.991 | 0.0000140 | 1174 |
| Loss of Function | 3.13 | 5 | 20.2 | 0.248 | 0.00000105 | 224 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000064 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Atypical MAPK protein. Phosphorylates microtubule- associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0999
Intolerance Scores
- LoFtool
- 0.270
- RVIS EVS
- -0.51
- RVIS percentile EVS
- 21.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.411
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |