MAPK11

Chr 22

mitogen-activated protein kinase 11

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

NCBI Gene: 5600 ENSG00000185386 UniProt: Q15759 OMIM: 602898

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.79

Clinical Summary— MAPK11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

33 VUS of 44 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.26

OE 0.45 (0.27–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

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?

LoF OE?0.45 (0.27–0.79)

0≤0.351.4

Missense OE?0.59 (0.51–0.69)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 9 / 19.9Missense obs/exp: 129 / 217.9Syn Z: 1.47

This gene — mechanism propensity

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

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	33	0	0	33
Likely Benign	0	0	3	3
Benign	0	1	0	1
Total	33	1	3	37

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

View in ClinVar →

143 pathogenic / likely-pathogenic (of 154) ClinVar copy-number / structural variants overlap MAPK11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →