MAPK11

Chr 22

mitogen-activated protein kinase 11

Also known as: P38B, P38BETA2, PRKM11, SAPK2, SAPK2B, p38-2, p38Beta

NCBI Gene: 5600ENSG00000185386UniProt: Q15759

This gene encodes a member of a family of protein kinases that are involved in the integration of biochemical signals for a wide variety of cellular processes, including cell proliferation, differentiation, transcriptional regulation, and development. The encoded protein can be activated by proinflammatory cytokines and environmental stresses through phosphorylation by mitogen activated protein kinase kinases (MKKs). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

195
ClinVar variants
140
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MAPK11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
140 Pathogenic / Likely Pathogenic· 43 VUS of 195 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.79LOEUF
pLI 0.000
Z-score 2.26
OE 0.45 (0.27–0.79)
Tolerant

Typical tolerance to LoF variation

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.
2.14Z-score
OE missense 0.59 (0.51–0.69)
129 obs / 217.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.45 (0.27–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.69)
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.0.81
0≤1.21.6
LoF obs/exp: 9 / 19.9Missense obs/exp: 129 / 217.9Syn Z: 1.47

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic139
Likely Pathogenic1
VUS43
Likely Benign3
Benign2
139
Pathogenic
1
Likely Pathogenic
43
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
139
0
139
Likely Pathogenic
0
0
1
0
1
VUS
0
33
10
0
43
Likely Benign
0
0
0
3
3
Benign
0
0
2
0
2
Total0331523188

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

View in ClinVar →

Protein Context — Lollipop Plot

MAPK11 · 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
TSPAN8(+) myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.
Fan G et al.·Sci Transl Med
2024Cohort
Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-α signaling.
Qi D et al.·Cancer Commun (Lond)
2023
Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.
Emelyanova A et al.·Biochemistry (Mosc)
2024
The Role of p38γ in Cancer: From review to outlook.
Xu W et al.·Int J Biol Sci
2021Review
Identifying Patients With Rapid Progression From Hormone-Sensitive to Castration-Resistant Prostate Cancer: A Retrospective Study.
Pan C et al.·Mol Cell Proteomics
2023Cohort
Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case.
Pfeifer M et al.·Orphanet J Rare Dis
2024Case report
Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway.
Jose S et al.·Mol Cell Biol
2025
Prognostic effect of VEGF gene variants in metastatic non-small-cell lung cancer patients.
Sullivan I et al.·Angiogenesis
2019Cohort
ANXA5 predicts prognosis and immune response and mediates proliferation and migration in head and neck squamous cell carcinoma.
Yang D et al.·Gene
2024
Single-Cell Transcriptomics of Endothelial Cells in Upper and Lower Human Esophageal Squamous Cell Carcinoma.
Sha Y et al.·Curr Oncol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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