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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RPL39L
ribosomal protein L39 like
Chromosome 3 · 3q27.3
NCBI Gene: 116832Ensembl: ENSG00000163923.11HGNC: HGNC:17094UniProt: Q96EH5
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingspermatogenesisstructural constituent of ribosomecytoplasmic translationinfluenzacoronary artery diseasecoronary atherosclerosisAbruptio Placentae
✦AI Summary

RPL39L is a male germ cell-specific ribosomal protein that replaces its paralog RPL39 in the ribosomes of developing sperm 1. As a structural component of the cytosolic large ribosomal subunit, RPL39L functions as an efficiency factor for cotranslational protein folding, particularly of proteins containing alpha-helical domains 2. CryoEM analysis reveals that RPL39L adopts two distinct conformations in the nascent peptide exit tunnel, creating a unique hydrophobic patch that facilitates efficient folding of its target proteins 2. Originally identified as testis-specific, RPL39L expression has been detected beyond germ cells in pluripotent stem cells, cancer cell lines, and various tissues 2. Its expression pattern is conserved across species in male germ cells and regulated by DNA hypomethylation and open chr3 3. Clinically, RPL39L serves as a biomarker for testicular aging and male fertility status 4, and shows association with hepatocellular carcinoma tumor grading 5. Additionally, elevated RPL39L expression correlates with poor survival in breast and colon cancer patients 6 and represents a prognostic marker in glioblastoma 7. These findings demonstrate that RPL39L exemplifies how ribosomal protein paralogs provide tunable, cell-type-specific translational control.

Sources cited
1
RPL39L is an efficiency factor for cotranslational folding of alpha-helical proteins; adopts distinct conformations creating a hydrophobic patch; expressed beyond germ cells in pluripotent cells and cancer lines
PMID: 39041433
2
RPL39L serves as a testicular aging biomarker and indicator of reproductive decline
PMID: 40153586
3
RPL39L shows male germ cell-specific expression pattern conserved across species; regulated by DNA hypomethylation and open chromatin
PMID: 39380204
4
RPL39L is testis-specific; expression correlates with hepatocellular carcinoma tumor grading and alpha-fetoprotein levels; recently evolved RP paralog with tissue-specific expression
PMID: 24452241
5
RPL39L is a retrotransposed X-linked gene expressed only in testis; functions as a ribosomal protein component
PMID: 12490704
6
High RPL39L expression correlates with poor survival in breast and colon cancer patients
PMID: 39940786
7
RPL39L identified as a prognostic marker in glioblastoma immune heterogeneity
PMID: 41026376
Disease Associationsⓘ20
influenzaOpen Targets
0.46Moderate
coronary artery diseaseOpen Targets
0.25Weak
coronary atherosclerosisOpen Targets
0.18Weak
Abruptio PlacentaeOpen Targets
0.13Weak
azoospermiaOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 65Open Targets
0.06Suggestive
spermatogenic failure 84Open Targets
0.06Suggestive
spermatogenic failure 93Open Targets
0.06Suggestive
spermatogenic failure 56Open Targets
0.06Suggestive
spermatogenic failure 92Open Targets
0.06Suggestive
spermatogenic failure 94Open Targets
0.06Suggestive
spermatogenic failure 51Open Targets
0.06Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.06Suggestive
spermatogenic failure 54Open Targets
0.06Suggestive
spermatogenic failure 72Open Targets
0.06Suggestive
spermatogenic failure 76Open Targets
0.06Suggestive
spermatogenic failure 80Open Targets
0.06Suggestive
spermatogenic failure 40Open Targets
0.06Suggestive
spermatogenic failure 58Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPL3Shared pathway100%RPS9Protein interaction100%RPS23Protein interaction100%RPL13AProtein interaction100%RPL27Protein interaction100%RPL29Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
60%
Heart
46%
Lung
19%
Ovary
19%
Liver
18%
Gene Interaction Network
Click a node to explore
RPL39LRPL3RPS9RPS23RPL13ARPL27RPL29
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q96EH5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.44LoF Tolerant
pLIⓘ
0.13Tolerant
Observed/Expected LoF0.57 [0.26–1.44]
RankingsWhere RPL39L stands among ~20K protein-coding genes
  • #14,799of 20,598
    Most Researched18
  • #14,797of 17,882
    Most Constrained (LOEUF)1.44
Genes detectedRPL39L
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains.
PMID: 39041433
Nucleic Acids Res · 2024
1.00
2
Exploring the Mechanisms of Testicular Aging: Advances in Biomarker Research.
PMID: 40153586
Aging Dis · 2025
0.90
3
SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine.
PMID: 39380204
Genomics Proteomics Bioinformatics · 2024
0.80
4
RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors.
PMID: 24452241
RNA Biol · 2014
0.70
5
A Computational Recognition Analysis of Promising Prognostic Biomarkers in Breast, Colon and Lung Cancer Patients.
PMID: 39940786
Int J Mol Sci · 2025
0.60