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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RPS6
ribosomal protein S6
Chromosome 9 · 9p22.1
NCBI Gene: 6194Ensembl: ENSG00000137154.14HGNC: HGNC:10429UniProt: A2A3R6
384PubMed Papers
20Diseases
6Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cell bodycytosolic small ribosomal subunitprotein bindingprotein kinase bindinginfluenzaDuchenne muscular dystrophycancercystic fibrosis
✦AI Summary

RPS6 (ribosomal protein S6) is a structural component of the 40S small ribosomal subunit that plays critical roles in protein synthesis regulation and cellular signaling 1. The protein undergoes phosphorylation on five evolutionarily conserved serine residues in response to various stimuli, which has been extensively studied for four decades 1. RPS6 phosphorylation occurs downstream of mTORC1 signaling and serves as a key indicator of mTORC1 activity 234. Beyond its structural role in ribosomes, RPS6 functions in selective mRNA translation control, influencing cell growth and proliferation 1. The protein can be post-translationally modified through ADP-ribosylation by PARP-16, which inhibits polysome assembly and maintains protein homeostasis in cancer cells by preventing toxic protein aggregation 5. RPS6 also serves as a marker for ribosome-associated processes, as demonstrated in studies using RPS6 antibodies for RNA-immunoprecipitation to identify ribosome-bound RNAs 6. The protein's phosphorylation status reflects nutritional states and stress responses, with decreased phosphorylation observed during amino acid starvation and mTOR pathway inhibition 78.

Sources cited
1
RPS6 phosphorylation occurs on five evolutionarily conserved serine residues and has been studied for four decades
PMID: 26614871
2
RPS6 phosphorylation serves as an indicator of mTORC1 activity in lipotoxicity studies
PMID: 34382907
3
RPS6 can be ADP-ribosylated by PARP-16, which inhibits polysome assembly and maintains protein homeostasis
PMID: 34314702
4
RPS6 phosphorylation reflects mTORC1 activity in autophagy regulation studies
PMID: 33734022
5
RPS6 phosphorylation indicates mTORC1 signaling in protein supplementation studies
PMID: 38762187
6
RPS6 antibodies can be used for RNA-immunoprecipitation to identify ribosome-bound RNAs
PMID: 32461121
7
RPS6 phosphorylation decreases during amino acid starvation and mTOR pathway inhibition
PMID: 31046771
8
RPS6 serves as a marker for mTOR pathway activity in autophagy studies
PMID: 33461384
Disease Associationsⓘ20
influenzaOpen Targets
0.46Moderate
Duchenne muscular dystrophyOpen Targets
0.46Moderate
cancerOpen Targets
0.39Weak
cystic fibrosisOpen Targets
0.39Weak
HypercholesterolemiaOpen Targets
0.38Weak
COVID-19Open Targets
0.37Weak
severe acute respiratory syndromeOpen Targets
0.37Weak
cardiovascular diseaseOpen Targets
0.29Weak
systemic lupus erythematosusOpen Targets
0.17Weak
neurodegenerative diseaseOpen Targets
0.14Weak
hemimegalencephalyOpen Targets
0.11Weak
neurocutaneous syndromeOpen Targets
0.10Weak
nutritional deficiency diseaseOpen Targets
0.10Suggestive
aniridiaOpen Targets
0.10Suggestive
Becker muscular dystrophyOpen Targets
0.10Suggestive
non-Hodgkins lymphomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
genetic disorderOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets6
ATALURENApproved
80S Ribosome modulator
Duchenne muscular dystrophy
CITATUZUMAB BOGATOXPhase I
Epithelial cell adhesion molecule binding agent
ELX-02Phase II
80S Ribosome modulator
cystic fibrosis
MT-3724Phase II
80S Ribosome inhibitor
diffuse large B-cell lymphoma
TELIMOMAB ARITOXPhase II
T-cell surface glycoprotein CD5 binding agent
hepatitis B virus infection
ZOLIMOMAB ARITOXPhase II
T-cell surface glycoprotein CD5 binding agent
arthritis
Related Genes
CSNK1A1Protein interaction100%CSNK1DProtein interaction100%EEF2Protein interaction100%EIF5AProtein interaction100%ETF1Protein interaction100%FAUProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
68%
Lung
40%
Liver
29%
Brain
28%
Heart
27%
Gene Interaction Network
Click a node to explore
RPS6CSNK1A1CSNK1DEEF2EIF5AETF1FAU
PROTEIN STRUCTURE
Preparing viewer…
PDB6F4Q · 1.12 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.17Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.03 [0.01–0.17]
RankingsWhere RPS6 stands among ~20K protein-coding genes
  • #779of 20,598
    Most Researched384 · top 5%
  • #760of 1,025
    FDA-Approved Drug Targets1
  • #277of 17,882
    Most Constrained (LOEUF)0.17 · top 5%
Genes detectedRPS6
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Ribosomal Protein S6 Phosphorylation: Four Decades of Research.
PMID: 26614871
Int Rev Cell Mol Biol · 2015
1.00
2
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
PMID: 34382907
Autophagy · 2022
0.90
3
Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers.
PMID: 34314702
Cell · 2021
0.80
4
Walking or body weight squat "activity snacks" increase dietary amino acid utilization for myofibrillar protein synthesis during prolonged sitting.
PMID: 35952344
J Appl Physiol (1985) · 2022
0.72
5
AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3.
PMID: 33734022
Autophagy · 2021
0.70