MAPK9

protein-coding

mitogen-activated protein kinase 9, the group of Mitogen-activated protein kinases

Gene summary

The protein encoded by this gene is a member of the 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. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Sep 2008]

Previous symbols:
  • PRKM9

MANE transcript

NM_002752.5

Inheritance

—

ClinVar variants

U:31B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr5:180,233,143-180,292,099

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~59.0 kb
Loading mutation effect viewer...

GenCC 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 MAPK9 variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002752.5. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
missense
28
clinvar
1
clinvar
29
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
2
Total00311032
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002752.5RefSeqNP_002743.311MANE Select
ENST00000452135.7EnsemblENSP00000394560.211MANE Select
NM_001135044.2RefSeqNP_001128516.16Standard
NM_001308244.1RefSeqNP_001295173.16Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mapk9Danio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)
  • T cell receptor signaling pathway - Homo sapiens (human)

Biological Process

  • protein phosphorylation
  • JNK cascade
  • JUN phosphorylation
  • response to mechanical stimulus
  • regulation of gene expression

Molecular Function

  • JUN kinase activity
  • MAP kinase activity
  • protein serine/threonine/tyrosine kinase activity
  • protein binding
  • ATP binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000452135
Coding exons
11
Length
58957
Individuals with no LoFs
125732
Homozygous LoFs
0
Heterozygous LoFs
16
Defined
125748
p
0.0000636
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.281382370.5820.00001292793
Missense (PolyPhen)40102.460.390381186
Synonymous0.8777484.20.8780.00000485782
Loss of Function3.39725.50.2750.00000136301

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000200.00020rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000800.000079rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:22441692}.;

Recessive Scores

pRec
0.800

Intolerance Scores

LoFtool
0.280
RVIS EVS
-0.63
RVIS percentile EVS
17.03

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.995

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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