RPS2

Chr 16

ribosomal protein S2

Also known as: LLREP3, S2, uS5

NCBI Gene: 6187ENSG00000140988UniProt: P15880OMIM: 603624

RPS2 encodes a ribosomal protein that is an essential component of the 40S ribosomal subunit and plays a critical role in protein synthesis and ribosome assembly. This gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.45), reflecting its fundamental importance for cellular function. Mutations in RPS2 cause developmental delays, intellectual disability, and growth retardation, typically following an autosomal dominant inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.45
Clinical Summary— RPS2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 35 VUS of 95 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.847
Z-score 2.72
OE 0.09 (0.03–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.85Z-score
OE missense 0.61 (0.53–0.72)
112 obs / 182.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.03–0.45)
0≤0.351.4
Missense OE0.61 (0.53–0.72)
0≤0.61.4
Synonymous OE1.56
0≤1.21.6
LoF obs/exp: 1 / 10.5Missense obs/exp: 112 / 182.5Syn Z: -3.82
DN
0.5181th %ile
GOF
0.1999th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.45

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic1
VUS35
Likely Benign2
Benign2
39
Pathogenic
1
Likely Pathogenic
35
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
1
0
1
VUS
0
18
17
0
35
Likely Benign
0
1
0
1
2
Benign
0
0
0
2
2
Total01957379

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RPS2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics analysis reveals the role of ribosome biogenesis in malignant clear cell renal cell carcinoma and the development of a machine learning-based prognostic model.
Xie Z et al.·Front Immunol
2025Functional
Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.
Pan R et al.·Anal Cell Pathol (Amst)
2022
Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists.
Baldini EH et al.·Int J Radiat Oncol Biol Phys
2015
Combined targeting poly (ADP-ribose) polymerase and receptor tyrosine kinase inhibits ovarian clear cell carcinoma progression through disrupted ribosome biogenesis.
Lin CY et al.·J Mol Med (Berl)
2026
Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation.
Baumhardt JM et al.·Mol Biol Cell
2020
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients