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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MAPK14
mitogen-activated protein kinase 14
Chromosome 6 · 6p21.31
NCBI Gene: 1432Ensembl: ENSG00000112062.13HGNC: HGNC:6876UniProt: A0ABB0MVC4
1,465PubMed Papers
20Diseases
29Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinaseTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cellular response to viruscellular response to lipopolysaccharideenzyme bindingprotein phosphatase bindingneurodegenerative diseaseneuroinflammatory disorderAlzheimer diseaseacute coronary syndrome
✦AI Summary

MAPK14 (p38α) is a stress-activated protein kinase that plays critical roles in cellular stress response and disease pathogenesis. The protein functions as a key mediator in stress signaling pathways, becoming activated in response to ribosome collisions during translational stress through the upstream kinase ZAK 1. MAPK14 exhibits diverse biological functions including regulation of cell fate decisions, with inhibition leading to uncontrolled mitotic entry through Cdc25 activation and Wee1 blocking, ultimately triggering mitotic catastrophe in cancer cells 2. The kinase demonstrates significant disease relevance across multiple conditions. In prolactinoma, MAPK14 expression is elevated and promotes tumor development, with knockout studies showing reduced prolactin production and tumor growth 3. In endometrial cancer, MAPK14 shapes the molecular landscape of high-grade tumors and promotes tumorigenic characteristics, particularly in 3D spheroid cultures that model malignant disease 4. Additionally, genetic variants in MAPK14 show associations with spondyloarthritis through family-based genome-wide association studies 5 and contribute to brain volume deficits in schizophrenia patients with marijuana misuse through interactions with cannabinoid receptor genes 6. These findings establish MAPK14 as a versatile kinase with therapeutic potential across inflammatory, neurological, and oncological conditions 7.

Sources cited
1
MAPK14 is activated by ribosome collisions through ZAK kinase during translational stress
PMID: 32610081
2
MAPK14 inhibition causes uncontrolled mitotic entry and mitotic catastrophe in cancer cells
PMID: 39820127
3
MAPK14 is elevated in prolactinoma and promotes tumor development and prolactin production
PMID: 32894113
4
MAPK14 shapes molecular landscape of endometrial cancer and promotes tumorigenic characteristics
PMID: 39708320
5
MAPK14 genetic variants are associated with spondyloarthritis
PMID: 27461236
6
MAPK14 variants interact with cannabinoid receptor genes affecting brain volumes in schizophrenia
PMID: 22850347
7
MAPK14 has therapeutic potential across multiple disease conditions
PMID: 33524689
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
neuroinflammatory disorderOpen Targets
0.46Moderate
Alzheimer diseaseOpen Targets
0.34Weak
acute coronary syndromeOpen Targets
0.34Weak
Parkinson diseaseOpen Targets
0.31Weak
multiple sclerosisOpen Targets
0.31Weak
lysosomal storage diseaseOpen Targets
0.30Weak
ankylosing spondylitisOpen Targets
0.30Weak
iridocyclitisOpen Targets
0.29Weak
Facioscapulohumeral dystrophyOpen Targets
0.29Weak
type 1 diabetes mellitusOpen Targets
0.29Weak
inflammatory spondylopathyOpen Targets
0.29Weak
spondyloarthropathyOpen Targets
0.28Weak
ulcerative colitisOpen Targets
0.28Weak
enteritisOpen Targets
0.27Weak
COVID-19Open Targets
0.27Weak
dermatitis herpetiformisOpen Targets
0.22Weak
celiac diseaseOpen Targets
0.21Weak
melanomaOpen Targets
0.21Weak
diabetes mellitusOpen Targets
0.19Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets29
ACUMAPIMODPhase II
MAP kinase p38 alpha inhibitor
chronic obstructive pulmonary disease
AMG-548UNKNOWN
MAP kinase p38 alpha inhibitor
inflammation
ARRY-797Phase III
MAP kinase p38 alpha inhibitor
AVE-9940Phase I
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
AZD-6703Phase I
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
AZD-7624Phase II
MAP kinase p38 alpha inhibitor
chronic obstructive pulmonary disease
BMS-582949Phase II
MAP kinase p38 alpha inhibitor
atherosclerosis
DILMAPIMODPhase II
MAP kinase p38 alpha inhibitor
acute lung injury
DORAMAPIMODPhase II
MAP kinase p38 alpha inhibitor
inflammatory bowel disease
FX-005Phase II/III
MAP kinase p38 alpha inhibitor
melanoma
GSK-610677Phase I
MAP kinase p38 alpha inhibitor
chronic obstructive pulmonary disease
ITX-5061Phase II
MAP kinase p38 alpha inhibitor
cardiovascular disease
LOSMAPIMODPhase III
MAP kinase p38 beta inhibitor
acute coronary syndrome
LY-3007113Phase I
MAP kinase p38 alpha inhibitor
metastatic malignant neoplasm
NEFLAMAPIMODPhase II
MAP kinase p38 alpha inhibitor
Alzheimer disease
PAMAPIMODPhase II
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
PEXMETINIBPhase I
MAP kinase p38 alpha inhibitor
arthritis
PF-03715455Phase II
MAP kinase p38 alpha inhibitor
chronic obstructive pulmonary disease
PG-760564Phase II
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
PH-797804Phase II
MAP kinase p38 alpha inhibitor
chronic obstructive pulmonary disease
R-1487Phase I
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
RALIMETINIBPhase I/II
MAP kinase p38 alpha inhibitor
RWJ-67657Phase I
MAP kinase p38 beta inhibitor
arthritis
SCIO-323PRECLINICAL
MAP kinase p38 alpha inhibitor
SEMAPIMODPhase II
MAP kinase p38 alpha inhibitor
TA-5493Phase I
MAP kinase p38 alpha inhibitor
inflammation
TAK-715Phase II
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
TALMAPIMODPhase II
MAP kinase p38 alpha inhibitor
rheumatoid arthritis
VX-702Phase II
MAP kinase p38 alpha inhibitor
coronary artery disease
Related Genes
MAP2K1Protein interaction100%MAP2K2Protein interaction100%RIPK2Protein interaction100%TAB1Protein interaction100%PTPN7Protein interaction100%TP53Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
93%
Liver
87%
Heart
53%
Brain
51%
Ovary
46%
Gene Interaction Network
Click a node to explore
MAPK14MAP2K1MAP2K2RIPK2TAB1PTPN7TP53
PROTEIN STRUCTURE
Preparing viewer…
PDB2FST · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.91Intolerant
Observed/Expected LoF0.31 [0.18–0.56]
RankingsWhere MAPK14 stands among ~20K protein-coding genes
  • #90of 20,598
    Most Researched1,465 · top 1%
  • #3,670of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedMAPK14
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate.
PMID: 32610081
Cell · 2020
1.00
2
The cellular thermal shift assay for evaluating drug target interactions in cells.
PMID: 25101824
Nat Protoc · 2014
0.90
3
Targeting ARNT attenuates chemoresistance through destabilizing p38α-MAPK signaling in glioblastoma.
PMID: 38806469
Cell Death Dis · 2024
0.84
4
NRAS
PMID: 32910840
Pigment Cell Melanoma Res · 2021
0.82
5
First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.
PMID: 39820127
Nat Cancer · 2025
0.80