RPS6KA2
Ribosomal Protein S6 Kinase A2
Gene Information Card
| Symbol | RPS6KA2 |
|---|---|
| Full Name | Ribosomal Protein S6 Kinase A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q27 |
| NCBI Gene ID | 6196 ncbi.nlm.nih.gov/gene/6196 |
| Ensembl ID | ENSG00000171234 |
| UniProt ID | Q15349 |
| OMIM ID | 601685 |
| HGNC ID | 10432 |
| Aliases | RSK3, MAPKAPK1C, S6K-alpha2, p90-RSK3 |
Description
RPS6KA2 encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase acts downstream of the MAPK/ERK signaling cascade and phosphorylates multiple substrates involved in cell growth, proliferation, differentiation, and survival. It is widely expressed and has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coffin-Lowry syndrome | Loss-of-function mutations in RPS6KA2 impair RSK3 activity, disrupting MAPK signaling and leading to intellectual disability and skeletal abnormalities. | OMIM #303600; ClinVar pathogenic variants |
| Non-small cell lung cancer | Overexpression and activating mutations in RPS6KA2 promote cell proliferation and resistance to apoptosis via enhanced ERK signaling. | COSMIC; PMID: 23481259 |
| Breast cancer | Amplification of RPS6KA2 locus and increased RSK3 expression correlate with poor prognosis and tamoxifen resistance. | PMID: 21536682; COSMIC |
| Ovarian cancer | RPS6KA2 mutations and copy number gains contribute to tumor progression and chemoresistance. | COSMIC; PMID: 22037554 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | High expression |
| HeLa | 8.9 | Medium expression |
| A549 | 7.2 | Medium expression |
| MCF7 | 6.8 | Medium expression |
| K562 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124G>A (p.Arg375Gln) | Missense | <0.1% | Reduced kinase activity; associated with Coffin-Lowry syndrome |
| c.1450C>T (p.Arg484Trp) | Missense | <0.1% | Loss of function; intellectual disability |
| c.1960G>A (p.Glu654Lys) | Missense | 0.2% | Gain of function; observed in lung adenocarcinoma |
| c.2113A>G (p.Thr705Ala) | Missense | 0.1% | Unknown effect; reported in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the kinase domain (e.g., Arg375Gln, Arg484Trp) reduce or abolish RSK3 activity, impairing downstream MAPK signaling and leading to Coffin-Lowry syndrome.
Gain of Function (GOF)
Activating mutations (e.g., Glu654Lys) enhance RSK3 kinase activity, promoting cell proliferation and survival in cancers.
Dominant Negative (DN)
No dominant-negative mutations have been reported for RPS6KA2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• mTOR signaling pathway (KEGG: hsa04150)
• ErbB signaling pathway (KEGG: hsa04012)
• Signaling by RSK (Reactome: R-HSA-444257)
Protein Summary
RPS6KA2 (RSK3) is a 733-amino acid serine/threonine kinase with two kinase domains. It is activated by ERK1/2 phosphorylation and phosphorylates substrates such as ribosomal protein S6, GSK3B, and transcription factors (CREB, c-Fos). RSK3 regulates cell cycle progression, translation, and survival. Dysregulation is linked to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPS6KA2 Knockout HEK293 Cell Line | EDJ-KQ231 | Human | 6196 | Details Get a Quote |
| RPS6KA2 Knockout HCT 116 Cell Line | EDJ-KQ19405 | Human | 6196 | Details Get a Quote |
| RPS6KA2 Knockout HeLa Cell Line | EDJ-KQ19406 | Human | 6196 | Details Get a Quote |
| RPS6KA2 Knockout A-549 Cell Line | EDJ-KQ62853 | Human | 6196 | Details Get a Quote |
