RIPK3: Receptor Interacting Serine/Threonine Kinase 3
Key regulator of necroptosis and inflammatory signaling
Gene Information Card
| Symbol | RIPK3 |
|---|---|
| Full Name | Receptor Interacting Serine/Threonine Kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 11035 ncbi.nlm.nih.gov/gene/11035 |
| Ensembl ID | ENSG00000129467 |
| UniProt ID | Q9Y572 |
| OMIM ID | 605817 |
| HGNC ID | 10021 |
| Aliases | RIP3, RIP-like kinase, RIPK-3 |
Description
RIPK3 encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The protein is a key mediator of necroptosis, a programmed form of necrotic cell death, and plays critical roles in inflammatory signaling, immune response, and tissue homeostasis. RIPK3 interacts with RIPK1 and MLKL to form the necrosome complex, leading to MLKL phosphorylation and membrane disruption. Dysregulation of RIPK3 is implicated in various diseases including inflammatory disorders, neurodegenerative diseases, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | RIPK3-mediated necroptosis contributes to intestinal epithelial cell death and inflammation | PMID: 28209917 |
| Acute pancreatitis | RIPK3-dependent necroptosis of acinar cells drives tissue damage | PMID: 26299943 |
| Myocardial infarction | RIPK3 promotes cardiomyocyte necroptosis during ischemia-reperfusion injury | PMID: 26980726 |
| Alzheimer's disease | RIPK3 activation in microglia and neurons contributes to neuroinflammation and cell death | PMID: 28854169 |
| Non-alcoholic steatohepatitis (NASH) | RIPK3 drives hepatocyte necroptosis and liver inflammation | PMID: 27542331 |
| Cutaneous melanoma | RIPK3 expression is frequently lost, promoting immune evasion and metastasis | PMID: 29507397 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Lung | 9.2 | Medium |
| Small intestine | 8.7 | Medium |
| Colon | 7.9 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
| Brain | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 14.2 | High expression |
| HEK 293 (embryonic kidney) | 12.1 | High expression |
| HeLa (cervical carcinoma) | 9.8 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 7.5 | Medium expression |
| SH-SY5Y (neuroblastoma) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.433C>T (p.Arg145*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1046G>A (p.Arg349His) | Missense | <0.01% | Unknown; predicted damaging |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of function; no translation |
| c.1240C>T (p.Arg414Cys) | Missense | <0.01% | Unknown; predicted benign |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg145*) that truncate the kinase domain or disrupt protein expression, leading to impaired necroptosis signaling.
Gain of Function (GOF)
Not well characterized; no recurrent activating mutations reported in cancer or other diseases.
Dominant Negative (DN)
Missense mutations in the kinase domain (e.g., p.Lys51Ala) can act as dominant-negative by binding RIPK1 but failing to phosphorylate MLKL, blocking necroptosis.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005524 (ATP binding) |
| • GO:0006468 (protein phosphorylation) | • GO:0006915 (apoptotic process) |
| • GO:0070266 (necroptotic process) | • GO:0035872 (nucleotide-binding domain |
| • leucine rich repeat containing receptor signaling pathway) | • GO:0043123 (positive regulation of I-kappaB kinase/NF-kappaB signaling) |
| • GO:0005737 (cytoplasm) | • GO:0005829 (cytosol) |
Pathways
• Necroptosis signaling (Reactome: R-HSA-5213460)
• RIPK1-mediated regulated necrosis (KEGG: hsa04217)
• TNF signaling pathway (KEGG: hsa04668)
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Programmed cell death (WikiPathways: WP254)
Protein Summary
RIPK3 is a 518-amino acid serine/threonine kinase with an N-terminal kinase domain, a central RIP homotypic interaction motif (RHIM), and a C-terminal domain. It forms the necrosome complex with RIPK1 and MLKL, leading to MLKL phosphorylation, oligomerization, and plasma membrane disruption, executing necroptosis. RIPK3 also activates NF-κB and inflammasome pathways. Its expression is highest in immune tissues and is frequently silenced in cancers via promoter methylation or deletion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIPK3 Knockout HEK293 Cell Line | EDJ-KQ981 | Human | 11035 | Details Get a Quote |
| RIPK3 Knockout HeLa Cell Line | EDJ-KQ55552 | Human | 11035 | Details Get a Quote |
| RIPK3 Knockout A-549 Cell Line | EDJ-KQ64046 | Human | 11035 | Details Get a Quote |
| RIPK3 Knockout HCT 116 Cell Line | EDJ-KQ72496 | Human | 11035 | Details Get a Quote |
| Ripk3 Knockout IBMDM Cell Line | EDC90297 | Mouse | 56532 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
