RIPK1: Receptor Interacting Serine/Threonine Kinase 1
A master regulator of cell death, inflammation, and necroptosis
Gene Information Card
| Symbol | RIPK1 |
|---|---|
| Full Name | Receptor Interacting Serine/Threonine Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p25.2 |
| NCBI Gene ID | 8737 ncbi.nlm.nih.gov/gene/8737 |
| Ensembl ID | ENSG00000137275 |
| UniProt ID | Q13546 |
| OMIM ID | 603453 |
| HGNC ID | 10019 |
| Aliases | RIP, RIP1, FLJ39204 |
Description
RIPK1 encodes a serine/threonine kinase that is a key mediator of programmed cell death and inflammatory signaling. It acts downstream of death receptors (e.g., TNFR1) and pattern recognition receptors, regulating NF-κB activation, apoptosis, and necroptosis. RIPK1 kinase activity is critical for necroptosis, while its scaffold function supports cell survival. Dysregulation of RIPK1 is implicated in inflammatory diseases, neurodegeneration, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | RIPK1 variants impair NF-κB signaling and increase apoptosis, leading to intestinal inflammation | PMID: 29779942 |
| Primary immunodeficiency with autoinflammation | Loss-of-function mutations in RIPK1 cause recurrent infections and systemic inflammation | PMID: 29779943 |
| Amyotrophic lateral sclerosis (ALS) | RIPK1 activation promotes necroptosis of motor neurons | PMID: 30936438 |
| Colorectal cancer | RIPK1 overexpression or mutation may promote tumor cell survival via NF-κB | PMID: 25605248 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Bone marrow | 10.5 | Medium |
| Small intestine | 8.3 | Low |
| Brain cortex | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.4 | Cervical cancer cell line |
| HEK 293 | 14.7 | Embryonic kidney cells |
| Jurkat | 12.1 | T-cell leukemia |
| HepG2 | 9.8 | Hepatocellular carcinoma |
| A549 | 7.5 | Lung adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1105C>T (p.Arg369*) | Nonsense | Rare | Loss of function; associated with immunodeficiency |
| c.1457G>A (p.Arg486His) | Missense | Rare | Impaired kinase activity; reduced necroptosis |
| c.1942C>T (p.Arg648Trp) | Missense | Rare | Altered NF-κB signaling; linked to IBD |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; severe autoinflammation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or abolish kinase activity, leading to impaired NF-κB signaling and increased susceptibility to infections.
Gain of Function (GOF)
Missense mutations that enhance kinase activity or stabilize RIPK1, promoting excessive necroptosis and inflammation.
Dominant Negative (DN)
Mutations that produce a truncated protein capable of interfering with wild-type RIPK1 function, often observed in autoinflammatory syndromes.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005515 (protein binding) |
| • GO:0006468 (protein phosphorylation) | • GO:0006915 (apoptotic process) |
| • GO:0070266 (necroptotic process) | • GO:0007250 (activation of NF-κB-inducing kinase activity) |
| • GO:0033209 (tumor necrosis factor-mediated signaling pathway) |
Pathways
• TNF signaling pathway (KEGG: hsa04668)
• Necroptosis (KEGG: hsa04217)
• NF-kappa B signaling pathway (KEGG: hsa04064)
• Apoptosis (KEGG: hsa04210)
• RIPK1-mediated regulated necrosis (Reactome: R-HSA-5213460)
Protein Summary
RIPK1 is a 671-amino acid protein containing an N-terminal serine/threonine kinase domain, an intermediate domain with a RIP homotypic interaction motif (RHIM), and a C-terminal death domain. The kinase domain is essential for necroptosis, while the RHIM mediates interaction with RIPK3 and TRIF. The death domain binds to TNFR1 and other death receptors. Post-translational modifications, including ubiquitination and phosphorylation, tightly regulate RIPK1 activity. Dysregulation of RIPK1 is a therapeutic target in inflammatory and neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIPK1 Knockout NCTC clone 929 Cell Line | EDJ-KQ50 | Mouse | 8737 | Details Get a Quote |
| RIPK1 Knockout HEK293 Cell Line | EDJ-KQ17897 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout A-549 Cell Line | EDJ-KQ19014 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout HCT 116 Cell Line | EDJ-KQ19016 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout HeLa Cell Line | EDJ-KQ19017 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout MDA-MB-231 Cell Line | EDJ-KZ43 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout HT-1080 Cell Line | EDJ-KZ429 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout SK-OV-3 Cell Line | EDJ-KZ430 | Human | 8737 | Details Get a Quote |
| RIPK1 Knockout HEK293T Cell Line | EDC08141 | Human | 8737 | Details Get a Quote |
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