MAP3K11

Chr 11

mitogen-activated protein kinase kinase kinase 11

Also known as: MEKK11, MLK-3, MLK3, PTK1, SPRK

NCBI Gene: 4296ENSG00000173327UniProt: Q16584

The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]

132
ClinVar variants
10
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— MAP3K11
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 118 VUS of 132 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.48LOEUF
pLI 0.011
Z-score 4.06
OE 0.29 (0.18–0.48)
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.
1.90Z-score
OE missense 0.77 (0.70–0.83)
401 obs / 523.6 exp
Tolerant

Mild missense constraint

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.0.29 (0.18–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.70–0.83)
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.1.07
0≤1.21.6
LoF obs/exp: 11 / 38.0Missense obs/exp: 401 / 523.6Syn Z: -0.83

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS118
Likely Benign4
7
Pathogenic
3
Likely Pathogenic
118
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
2
0
3
VUS
0
113
5
0
118
Likely Benign
0
2
0
2
4
Benign
0
0
0
0
0
Total0116142132

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

View in ClinVar →

Protein Context — Lollipop Plot

MAP3K11 · 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
HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.
Ng NHJ et al.·Nat Commun
2024
MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma.
Liu PF et al.·J Cell Physiol
2022
Identification of Genes Required for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells In Vitro.
Kohrt SE et al.·Mol Cancer Ther
2021
Aberrant DNA Methylation in Keratoacanthoma.
Nobeyama Y et al.·PLoS One
2016
Immunosuppressive MAP3K11 as an independent risk factor for progression-free survival promotes prostate cancer metastasis by regulating epithelial-mesenchymal transition.
Zhang Z et al.·Biochem Biophys Res Commun
2025
A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy.
Silva CT et al.·BMC Med Genomics
2018
Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis.
Dong T et al.·Sci Rep
2024
Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance.
Wei S et al.·Hereditas
2025
Construction and experimental validation of a novel ferroptosis-related gene signature for myelodysplastic syndromes.
Zhu Y et al.·Immun Inflamm Dis
2024
Combination of bulk RNA sequencing and scRNA sequencing uncover the molecular characteristics of MAPK signaling in kidney renal clear cell carcinoma.
Li X et al.·Aging (Albany NY)
2024
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