MAPK11

Chr 22

mitogen-activated protein kinase 11

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

The protein is a serine/threonine kinase that functions as an essential component of the p38 MAP kinase signaling pathway, regulating cellular responses to inflammatory cytokines and environmental stress through phosphorylation of transcription factors and other downstream targets. MAPK11 is highly tolerant to loss-of-function variation (LOEUF 0.79), and no Mendelian diseases have been definitively associated with mutations in this gene to date. The gene's tolerance to variation suggests that if pathogenic variants are identified in the future, they would likely be very rare.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.79
Clinical SummaryMAPK11
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.000
Z-score 2.26
OE 0.45 (0.270.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.14Z-score
OE missense 0.59 (0.510.69)
129 obs / 217.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.45 (0.270.79)
00.351.4
Missense OE0.59 (0.510.69)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 9 / 19.9Missense obs/exp: 129 / 217.9Syn Z: 1.47
DN
0.7230th %ile
GOF
0.6735th %ile
LOF
0.2971th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →