RIPK4: Receptor Interacting Serine/Threonine Kinase 4
A key regulator of keratinocyte differentiation, Wnt signaling, and craniofacial development; implicated in Bartsocas-Papas syndrome and squamous cell carcinoma.
Gene Information Card
| Symbol | RIPK4 |
|---|---|
| Full Name | Receptor Interacting Serine/Threonine Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 54101 ncbi.nlm.nih.gov/gene/54101 |
| Ensembl ID | ENSG00000142168 |
| UniProt ID | P57078 |
| OMIM ID | 605706 |
| HGNC ID | 496 |
| Aliases | ANKRD3, DIK, PKK, RIP4 |
Description
RIPK4 encodes a serine/threonine kinase belonging to the receptor-interacting protein (RIP) family. The protein contains an N-terminal kinase domain and a C-terminal ankyrin repeat domain. It plays a critical role in keratinocyte differentiation, epidermal development, and Wnt signaling by interacting with protein kinase C delta (PRKCD) and regulating the transcription factor TP63. Mutations in RIPK4 cause Bartsocas-Papas syndrome, and altered expression is associated with squamous cell carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bartsocas-Papas syndrome (BPS) | Loss-of-function mutations in RIPK4 disrupt keratinocyte differentiation and craniofacial development, leading to severe popliteal pterygium, facial clefts, and syndactyly. | OMIM #225000; multiple homozygous/compound heterozygous mutations identified in affected families. |
| Squamous cell carcinoma (SCC) | RIPK4 overexpression or aberrant activation promotes cell proliferation and invasion via Wnt/β-catenin and NF-κB pathways. | COSMIC; increased RIPK4 mRNA and protein levels in SCC tumors compared to normal tissue. |
| Non-small cell lung cancer (NSCLC) | RIPK4 upregulation correlates with poor prognosis and may drive tumor growth through kinase-dependent signaling. | NCBI Gene; expression profiling studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | High |
| Esophagus | 8.3 | Medium |
| Lung | 5.1 | Medium |
| Breast | 3.2 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High endogenous expression |
| A431 (epidermoid carcinoma) | 11.7 | Overexpressed relative to normal skin |
| NCI-H1299 (lung carcinoma) | 6.4 | Moderate expression |
| MCF7 (breast carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35*) | Nonsense | Homozygous in BPS | Loss of function; truncated protein lacking kinase domain |
| c.472G>A (p.Gly158Arg) | Missense | Homozygous in BPS | Impaired kinase activity; reduced autophosphorylation |
| c.1262G>A (p.Arg421Gln) | Missense | Somatic (SCC) | Gain of function; increased NF-κB activation |
| c.1745T>C (p.Leu582Pro) | Missense | Somatic (lung cancer) | Unknown; located in ankyrin repeat domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations in the kinase domain (e.g., p.Arg35*, p.Gly158Arg) that abolish catalytic activity or destabilize the protein, leading to Bartsocas-Papas syndrome.
Gain of Function (GOF)
Somatic missense mutations (e.g., p.Arg421Gln) that enhance kinase activity and downstream NF-κB signaling, contributing to squamous cell carcinoma progression.
Dominant Negative (DN)
Not well documented; however, truncated forms lacking the ankyrin repeats may interfere with wild-type RIPK4 function in vitro.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• NF-kappaB signaling (KEGG: hsa04064)
• Keratinocyte differentiation (GO:0030216)
Protein Summary
RIPK4 is a 784-amino acid serine/threonine kinase with a molecular weight of approximately 87 kDa. It localizes to the cytoplasm and plasma membrane. The kinase domain (residues 1–300) is essential for catalytic activity, while the C-terminal ankyrin repeats (residues 500–784) mediate protein-protein interactions, including binding to PRKCD and TP63. RIPK4 regulates epidermal differentiation by modulating Wnt/β-catenin signaling and NF-κB activation. Post-translational modifications include autophosphorylation and phosphorylation by upstream kinases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RIPK4 Knockout HEK293 Cell Line | EDJ-KQ2708 | Human | 54101 | Details Get a Quote |
| RIPK4 Knockout A-549 Cell Line | EDJ-KQ23553 | Human | 54101 | Details Get a Quote |
| RIPK4 Knockout HCT 116 Cell Line | EDJ-KQ23554 | Human | 54101 | Details Get a Quote |
| RIPK4 Knockout HeLa Cell Line | EDJ-KQ23555 | Human | 54101 | Details Get a Quote |
