RPS6

Chr 9

ribosomal protein S6

ENSG00000137154UniProt: P62753

Component of the 40S small ribosomal subunit (PubMed:23636399, PubMed:8706699). Plays an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA (PubMed:17220279). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797)

0
ClinVar variants
0
Pathogenic / LP
0.98
pLI score· haploinsufficient
1
Active trials
Clinical Summary— RPS6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (3)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 0.976
Z-score 3.14
OE 0.00 (0.00–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.33Z-score
OE missense 0.70 (0.59–0.82)
107 obs / 153.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.59–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.80
0≤1.21.6
LoF obs/exp: 0 / 11.4Missense obs/exp: 107 / 153.5Syn Z: -4.36

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RPS6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
Liu K et al.·Autophagy
2022
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
MTOR signaling regulates the development of airway mucous cell metaplasia associated with severe asthma.
Kudrna KM et al.·JCI Insight
2025
PSMB10 maintains the stemness of chemotherapeutic drug-resistant leukemia cells by inhibiting senescence and cytotoxic T lymphocyte-mediated killing in a ubiquitinated degradation manner.
Ma X et al.·J Exp Clin Cancer Res
2025
The Neurobeachin-like 2 protein (NBEAL2) controls the homeostatic level of the ribosomal protein RPS6 in mast cells.
Wegner P et al.·Immunology
2024
Quantitative proteomics and phosphoproteomics of PP2A-PPP2R5D variants reveal deregulation of RPS6 phosphorylation via converging signaling cascades.
Smolen KA et al.·J Biol Chem
2023
[Stable Expression of Coagulation Factors by RPS6 Promoter].
Zhang WH et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2023
Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53-dependent.
Comerford SA et al.·PLoS Genet
2023
Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle.
Holowaty MNH et al.·Amino Acids
2023
Midkine Promotes Metastasis and Therapeutic Resistance via mTOR/RPS6 in Uveal Melanoma.
Karg MM et al.·Mol Cancer Res
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Protein levels of p-mTOR and p-RPS6 in cumulus cells serve as non-invasive biomarkers for embryo quality and pregnancy outcome in IVF.
Li J et al.·J Assist Reprod Genet
2026
Vesicular Rps6 Released by Astrocytes in an Experimental Model of AD Regulates Local Translation and Enhances Synaptic Integrity in Neurones.
Gamarra M et al.·J Extracell Vesicles
2025🔓 Open AccessFunctional
Translation of nervous necrosis virus involves eIF4E but not RPS6 phosphorylation and viral particle assembly in remodeled microtubule-organizing center.
Bajpai V et al.·Virol J
2025🔓 Open AccessFunctional
Histamine-induced RPS6 phosphorylation in dendritic cells is associated with the severity of peanut allergic reactions.
Fauchère F et al.·JCI Insight
2025🔓 Open Access
Possible involvement of p60-S6K1 in accelerating RPS6 phosphorylation for rapid recovery from skeletal muscle disuse atrophy.
Inoue T et al.·Lab Anim Res
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Kidney Neoplasms

MRI Functional Imaging Characteristics and Fat Quantification of CT-fat-free Renal Neoplasms: Relationships With Histological Classifications and Molecular Markers

ACTIVE NOT RECRUITING
NCT06126159Phase NAChang Gung Memorial HospitalStarted 2019-02-11
multiparametric and fat-detection magnetic resonance imaging (MRI)

External Resources

Links to major genomics databases and tools