RPS6: Ribosomal Protein S6 – A Key Component of the 40S Ribosomal Subunit
Essential for translation initiation, cell growth, and proliferation; implicated in cancer and developmental disorders
Gene Information Card
| Symbol | RPS6 |
|---|---|
| Full Name | Ribosomal Protein S6 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p22.1 |
| NCBI Gene ID | 6194 ncbi.nlm.nih.gov/gene/6194 |
| Ensembl ID | ENSG00000137154 |
| UniProt ID | P62753 |
| OMIM ID | 180460 |
| HGNC ID | 10429 |
| Aliases | S6, eS6, 40S ribosomal protein S6 |
Description
RPS6 encodes the ribosomal protein S6, a component of the 40S small ribosomal subunit. This protein is a major substrate of the p70 S6 kinase (S6K) and is phosphorylated in response to growth factors, nutrients, and mitogens. Phosphorylation of RPS6 enhances translation of mRNAs containing 5' terminal oligopyrimidine (TOP) tracts, thereby regulating cell growth, proliferation, and metabolism. RPS6 is also involved in ribosome biogenesis and has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 82 (SPG82) | Loss-of-function mutations in RPS6 impair ribosomal function, leading to axonal degeneration and motor neuron dysfunction. | ClinVar; OMIM #180460 |
| Colorectal Cancer | Overexpression and hyperphosphorylation of RPS6 promote translation of oncogenic mRNAs, driving tumor growth. | COSMIC; NCBI Gene |
| Breast Cancer | Increased RPS6 phosphorylation via PI3K/AKT/mTOR pathway correlates with poor prognosis. | COSMIC; PubMed |
| Developmental Delay and Intellectual Disability | De novo missense variants in RPS6 disrupt ribosomal assembly and protein synthesis, affecting neurodevelopment. | ClinVar; OMIM #180460 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 27.5 | High |
| Heart | 22.3 | High |
| Liver | 18.9 | Medium |
| Kidney | 20.1 | Medium |
| Testis | 30.2 | High |
| Lung | 15.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.1 | High expression; commonly used for functional studies |
| HeLa | 28.7 | High expression; cervical cancer cell line |
| K562 | 25.3 | High expression; leukemia cell line |
| MCF7 | 22.0 | Medium expression; breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50Cys) | Missense | Rare | Loss of function; associated with SPG82 |
| c.307G>A (p.Gly103Arg) | Missense | Rare | Loss of function; linked to developmental delay |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; likely pathogenic |
| c.485_486del (p.Glu162Glyfs*3) | Frameshift | Rare | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations in RPS6 are loss-of-function, leading to reduced ribosomal protein S6 levels or impaired ribosome assembly, as seen in SPG82 and developmental disorders.
Gain of Function (GOF)
No confirmed gain-of-function mutations have been reported in RPS6. Overexpression or hyperphosphorylation is observed in cancers but is not due to activating mutations.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg50Cys) may exert dominant-negative effects by incorporating into ribosomes and disrupting function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (KEGG hsa04150)
• Ribosome (KEGG hsa03010)
• PI3K-Akt signaling pathway (KEGG hsa04151)
• Insulin signaling pathway (KEGG hsa04910)
Protein Summary
Ribosomal protein S6 (RPS6) is a 249-amino-acid protein (molecular weight ~28.6 kDa) located in the cytoplasm as part of the 40S ribosomal subunit. It contains multiple serine residues (Ser235, Ser236, Ser240, Ser244) that are phosphorylated by S6K1/2 in response to mTOR activation. Phosphorylated RPS6 enhances translation of TOP mRNAs, which encode ribosomal proteins and elongation factors, thereby promoting cell growth and proliferation. The protein also interacts with eIF3 and other translation initiation factors. Mutations in RPS6 cause ribosomal dysfunction and are linked to neurodegenerative and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPS6KB2 Knockout HEK293 Cell Line | EDJ-KQ125 | Human | 6199 | Details Get a Quote |
| RPS6KA2 Knockout HEK293 Cell Line | EDJ-KQ231 | Human | 6196 | Details Get a Quote |
| RPS6KB1 Knockout HEK293 Cell Line | EDJ-KQ398 | Human | 6198 | Details Get a Quote |
| RPS6KA1 Knockout HEK293 Cell Line | EDJ-KQ749 | Human | 6195 | Details Get a Quote |
| RPS6KA3 Knockout HEK293 Cell Line | EDJ-KQ751 | Human | 6197 | Details Get a Quote |
| RPS6KA4 Knockout HEK293 Cell Line | EDJ-KQ752 | Human | 8986 | Details Get a Quote |
| RPS6KA5 Knockout HEK293 Cell Line | EDJ-KQ753 | Human | 9252 | Details Get a Quote |
| RPS6KA6 Knockout HEK293 Cell Line | EDJ-KQ754 | Human | 27330 | Details Get a Quote |
| RPS6KC1 Knockout HEK293 Cell Line | EDJ-KQ8611 | Human | 26750 | Details Get a Quote |
| RPS6KL1 Knockout HEK293 Cell Line | EDJ-KQ9886 | Human | 83694 | Details Get a Quote |
| RPS6KA4 Knockout HeLa Cell Line | EDJ-KQ18243 | Human | 8986 | Details Get a Quote |
| RPS6KB1 Knockout A-549 Cell Line | EDJ-KQ18627 | Human | 6198 | Details Get a Quote |
| RPS6KB1 Knockout HCT 116 Cell Line | EDJ-KQ18628 | Human | 6198 | Details Get a Quote |
| RPS6KB1 Knockout HeLa Cell Line | EDJ-KQ18629 | Human | 6198 | Details Get a Quote |
| RPS6KB2 Knockout A-549 Cell Line | EDJ-KQ18630 | Human | 6199 | Details Get a Quote |
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