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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MAP3K11
mitogen-activated protein kinase kinase kinase 11
Chromosome 11 · 11q13.1
NCBI Gene: 4296Ensembl: ENSG00000173327.10HGNC: HGNC:6850UniProt: Q16584
124PubMed Papers
20Diseases
1Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cell cycle G1/S phase transitionprotein serine/threonine kinase activityJUN kinase kinase kinase activityMAP kinase kinase kinase activityneurodegenerative diseaseParkinson diseaseAlzheimer diseaselysosomal storage disease
✦AI Summary

MAP3K11 (Mixed Lineage Kinase 3, MLK3) is a serine/threonine kinase that serves as a critical upstream regulator of multiple MAPK signaling pathways. The protein activates JUN N-terminal kinase (JNK) signaling through phosphorylation of downstream kinases MAP2K4/MKK4 and MAP2K7/MKK7, and is required for serum-stimulated cell proliferation and cytokine-mediated activation of p38, ERK, and JNK pathways 1. MAP3K11 also regulates autophagy by phosphorylating ATG4B at serine residues 383/392, thereby enhancing its proteolytic activity and promoting autophagic flux 2. In disease contexts, MAP3K11 exhibits oncogenic properties in hepatocellular carcinoma by promoting TGFβ signaling, epithelial-mesenchymal transition, and hepatic stellate cell activation 3. Elevated MAP3K11 expression correlates with poor prognosis in oral squamous cell carcinoma when co-expressed with ATG4B 2. Additionally, rare variants in MAP3K11 have been associated with left ventricular hypertrophy through its role as a pro-apoptotic kinase affecting cardiomyocyte survival 4. The gene has also been identified as a potential diagnostic marker in atherosclerosis with rheumatoid arthritis 5 and as a risk factor for gout development 6.

Sources cited
1
MAP3K11 is targeted by miR-125a-5p and activates JNK MAPK signaling pathway
PMID: 31527306
2
MAP3K11 phosphorylates ATG4B at S383/392 to promote autophagy and correlates with poor survival in oral cancer
PMID: 36103355
3
MAP3K11 promotes hepatocellular carcinoma progression via TGFβ pathway and EMT
PMID: 38858590
4
MAP3K11 variants associated with left ventricular hypertrophy and cardiomyocyte apoptosis
PMID: 29506515
5
MAP3K11 identified as immune-related hub gene for atherosclerosis with rheumatoid arthritis diagnosis
PMID: 36969166
6
MAP3K11 potentially elevates gout risk through genome-wide association analysis
PMID: 38831441
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
Parkinson diseaseOpen Targets
0.32Weak
Alzheimer diseaseOpen Targets
0.30Weak
lysosomal storage diseaseOpen Targets
0.29Weak
multiple sclerosisOpen Targets
0.29Weak
Moyamoya diseaseOpen Targets
0.26Weak
acneOpen Targets
0.24Weak
asthmaOpen Targets
0.19Weak
neoplasmOpen Targets
0.10Weak
breast cancerOpen Targets
0.10Weak
angina pectorisOpen Targets
0.10Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.07Suggestive
liver cancerOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
Hypomaturation amelogenesis imperfectaOpen Targets
0.07Suggestive
Hypoplastic amelogenesis imperfectaOpen Targets
0.06Suggestive
hereditary palmoplantar keratoderma, Gamborg-Nielsen typeOpen Targets
0.06Suggestive
Pathogenic Variants1
NM_002419.4(MAP3K11):c.847G>A (p.Ala283Thr)Likely pathogenic
Moyamoya angiopathy
☆☆☆☆→ Residue 283
View on ClinVar ↗
Drug Targets1
CEP-1347Phase II/III
Mitogen-activated protein kinase kinase kinase 10 inhibitor
asthma
Related Genes
MAP2K7Protein interaction100%MAPK8IP2Protein interaction100%CDC42Protein interaction99%MAPK8IP1Protein interaction99%MAPK8IP3Protein interaction93%MAP4K1Protein interaction92%
Tissue Expression6 tissues
Liver
100%
Lung
78%
Bone Marrow
34%
Brain
32%
Ovary
26%
Heart
25%
Gene Interaction Network
Click a node to explore
MAP3K11MAP2K7MAPK8IP2CDC42MAPK8IP1MAPK8IP3MAP4K1
PROTEIN STRUCTURE
Preparing viewer…
PDB5K26 · 1.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.79LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.49–0.79]
RankingsWhere MAP3K11 stands among ~20K protein-coding genes
  • #3,800of 20,598
    Most Researched124 · top quartile
  • #4,823of 5,498
    Most Pathogenic Variants1
  • #6,524of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedMAP3K11
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of immune-related genes in diagnosing atherosclerosis with rheumatoid arthritis through bioinformatics analysis and machine learning.
PMID: 36969166
Front Immunol · 2023
1.00
2
HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.
PMID: 38909044
Nat Commun · 2024
0.90
3
Single-cell and genome-wide Mendelian randomization identifies causative genes for gout.
PMID: 38831441
Arthritis Res Ther · 2024
0.80
4
MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma.
PMID: 36103355
J Cell Physiol · 2022
0.70
5
A combined linkage, microarray and exome analysis suggests MAP3K11 as a candidate gene for left ventricular hypertrophy.
PMID: 29506515
BMC Med Genomics · 2018
0.60