MAPK14

Chr 6

mitogen-activated protein kinase 14

Also known as: CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2, PRKM14, PRKM15

NCBI Gene: 1432ENSG00000112062UniProt: Q16539

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 is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

39
ClinVar variants
8
Pathogenic / LP
0.37
pLI score
0
Active trials
Clinical Summary— MAPK14
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 25 VUS of 39 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.47LOEUF
pLI 0.375
Z-score 3.39
OE 0.22 (0.12–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.31Z-score
OE missense 0.35 (0.29–0.42)
71 obs / 204.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.12–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.29–0.42)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 5 / 22.2Missense obs/exp: 71 / 204.1Syn Z: -0.35

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS25
Likely Benign5
Benign1
7
Pathogenic
1
Likely Pathogenic
25
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
23
2
0
25
Likely Benign
0
3
0
2
5
Benign
0
1
0
0
1
Total02710239

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAPK14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis.
Weng J et al.·Ann Med
2023Review
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
EGFR tyrosine kinase activity and Rab GTPases coordinate EGFR trafficking to regulate macrophage activation in sepsis.
Zhang X et al.·Cell Death Dis
2022
Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma.
Wang C et al.·BMC Complement Med Ther
2023Functional
Respiratory toxicity mechanism of 6PPD and 6PPD-quinone: An integrated study based on network toxicology and molecular docking.
Li G et al.·Ecotoxicol Environ Saf
2025Functional
Based on UPLC-Q-TOF/MS and Network Pharmacology to Explore the Mechanism of Qingre Lishi Decoction in the Treatment of Psoriasis.
Wei J et al.·Drug Des Devel Ther
2024Functional
RPS15 interacted with IGF2BP1 to promote esophageal squamous cell carcinoma development via recognizing m(6)A modification.
Zhao Y et al.·Signal Transduct Target Ther
2023
METTL3-mediated m6A modification of PAK6 drives cervical cancer progression through activating MAPK14.
Zhu ZM et al.·Int J Biol Macromol
2025
Network Pharmacology Analysis to Explore the Pharmacological Mechanism of Effective Chinese Medicines in Treating Metastatic Colorectal Cancer using Meta-Analysis Approach.
Zhu Y et al.·Am J Chin Med
2021Meta-analysis
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Zhang Y et al.·Front Immunol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Comprehensive Analysis of Immunomodulatory-Related Genes Reveals MAPK14-Associated Myeloid-Derived Suppressor Cells Infiltration in Pediatric Sepsis.
Shi J et al.·J Inflamm Res
2026🔓 Open Access
UBL4A as a suppressor of intracerebral hemorrhage by binding to MAPK14 and promoting MAPK14 ubiquitination.
Ou Y et al.·Genes Genomics
2026
MAPK14 converges on key transcriptional machinery to promote vascular smooth muscle cell degeneration in abdominal aortic aneurysm.
Wu X et al.·Signal Transduct Target Ther
2026🔓 Open Access
SLC39A10 drives M2 macrophage polarization and gastric cancer progression through the MAPK14(p38α) pathway.
Liang Y et al.·iScience
2026🔓 Open Access
Gentisic acid ameliorates lumbar disc herniation by regulating M1/M2 Polarization via the MAPK14/S100A9/Rac1/2 pathway.
Li S et al.·Cell Biol Toxicol
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools