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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RIPK2
receptor interacting serine/threonine kinase 2
Chromosome 8 · 8q21.3
NCBI Gene: 8767Ensembl: ENSG00000104312.9HGNC: HGNC:10020UniProt: A0A0S2Z4Z8
212PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisKinase
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
toll-like receptor 2 signaling pathwaypositive regulation of canonical NF-kappaB signal transductionsignaling receptor bindingprotein bindingleprosyCrohn's diseaseneurodegenerative diseaseglomerulonephritis
✦AI Summary

RIPK2 is a serine/threonine kinase essential for innate and adaptive immune responses 1. It functions as a key effector of NOD1 and NOD2 signaling pathways by recruiting to activated pattern recognition receptors upon bacterial peptidoglycan detection, where it undergoes autophosphorylation and K63-linked polyubiquitination by XIAP and BIRC proteins, as well as linear polyubiquitination by the LUBAC complex 1. These ubiquitin modifications enable RIPK2 to scaffold downstream signaling complexes that activate NF-κB and MAPK pathways, ultimately promoting inflammatory cytokine production 1. Notably, RIPK2's kinase activity is dispensable for NOD-mediated signaling, functioning primarily as a scaffolding protein 1. RIPK2 also participates in T-cell receptor signaling and NOD1-dependent hematopoietic stem cell specification through NF-κB activation 2. Dysregulation of RIPK2 has clinical implications: genetic variants in RIPK2 are associated with Crohn's disease susceptibility, and RIPK2 plays roles in neuroinflammatory diseases including Alzheimer's disease and multiple sclerosis 13. Recent evidence demonstrates RIPK2 is a therapeutic target in pancreatic cancer, where tumor-intrinsic RIPK2 drives immune evasion by impairing MHC class I presentation, and RIPK2 inhibition combined with anti-PD-1 immunotherapy enhances anti-tumor immunity 4.

Sources cited
1
RIPK2 is essential for innate immune responses; acts as key NOD1/NOD2 effector with K63 and linear ubiquitination, activating NF-κB and MAPK pathways; kinase activity dispensable for NOD signaling; role in neuroinflammation and neurological diseases
PMID: 38349514
2
NOD1-RIPK2-NF-κB inflammatory pathway controls hematopoietic stem cell specification from endothelial cells
PMID: 37996457
3
RIPK2 involvement in IBD pathogenesis through NOD2 signaling and intestinal homeostasis
PMID: 31286804
4
RIPK2 is a driver of immune evasion in pancreatic cancer by impairing MHC class I surface levels; RIPK2 inhibition sensitizes tumors to anti-PD-1 immunotherapy
PMID: 37824278
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
leprosyOpen Targets
0.50Moderate
Crohn's diseaseOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.34Weak
glomerulonephritisOpen Targets
0.29Weak
Abnormality of the skeletal systemOpen Targets
0.25Weak
Oral ulcerOpen Targets
0.22Weak
benign chondrogenic neoplasmOpen Targets
0.20Weak
dermatophytosisOpen Targets
0.20Weak
placental retentionOpen Targets
0.19Weak
liver diseaseOpen Targets
0.19Weak
sialolithiasisOpen Targets
0.17Weak
circadian rhythm sleep disorderOpen Targets
0.17Weak
Precordial painOpen Targets
0.17Weak
esophageal cancerOpen Targets
0.16Weak
hypotensionOpen Targets
0.16Weak
osteoarthritisOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
gliomaOpen Targets
0.10Weak
ulcerative colitisOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RIPK1Protein interaction100%MAP3K7Protein interaction100%MAPK14Protein interaction100%TAB2Protein interaction100%SHARPINProtein interaction100%RBCK1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
14%
Heart
10%
Brain
10%
Liver
6%
Ovary
5%
Gene Interaction Network
Click a node to explore
RIPK2RIPK1MAP3K7MAPK14TAB2SHARPINRBCK1
PROTEIN STRUCTURE
Preparing viewer…
PDB7OBS · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.29 [0.17–0.53]
RankingsWhere RIPK2 stands among ~20K protein-coding genes
  • #1,966of 20,598
    Most Researched212 · top 10%
  • #3,337of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedRIPK2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Proteogenomics connects somatic mutations to signalling in breast cancer.
PMID: 27251275
Nature · 2016
1.00
2
Ripks and Neuroinflammation.
PMID: 38349514
Mol Neurobiol · 2024
0.90
3
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.
PMID: 31286804
Autophagy · 2020
0.80
4
Emerging views of mitophagy in immunity and autoimmune diseases.
PMID: 30951392
Autophagy · 2020
0.70
5
Receptor-interacting Protein Kinase 2 Is an Immunotherapy Target in Pancreatic Cancer.
PMID: 37824278
Cancer Discov · 2024
0.60