RPL3

Chr 22

ribosomal protein L3

Also known as: ASC-1, L3, TARBP-B, uL3

NCBI Gene: 6122ENSG00000100316UniProt: P39023

Ribosomes, the complexes that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

93
ClinVar variants
0
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RPL3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
93 total variants — no pathogenic classifications of 93 total submissions

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.
0.24LOEUF
pLI 0.994
Z-score 3.92
OE 0.05 (0.02–0.24)
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.
1.56Z-score
OE missense 0.72 (0.64–0.82)
178 obs / 246.9 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.0.05 (0.02–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.64–0.82)
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.1.33
0≤1.21.6
LoF obs/exp: 1 / 19.8Missense obs/exp: 178 / 246.9Syn Z: -2.45

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

RPL3 · 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
Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.
Xie H et al.·Adv Sci (Weinh)
2026Functional
Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP.
Esposito D et al.·Oncotarget
2014
Genetic Determinants of Survival in Parkinson's Disease in the Asian Population.
Li C et al.·Mov Disord
2022
rpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment.
Russo A et al.·Sci Rep
2016
Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy.
Murphy MR et al.·Nat Cardiovasc Res
2026Case report
Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.
Novak T et al.·Front Immunol
2023
Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.
Sabater-Lleal M et al.·Circulation
2019Meta-analysis
Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles.
Russo A et al.·Oncotarget
2016
Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.
Pan R et al.·Anal Cell Pathol (Amst)
2022
Epsin Family Member 3 and Ribosome-Related Genes Are Associated with Late Metastasis in Estrogen Receptor-Positive Breast Cancer and Long-Term Survival in Non-Small Cell Lung Cancer Using a Genome-Wide Identification and Validation Strategy.
Hellwig B et al.·PLoS One
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools