RPL23 Gene

RPL23 Gene — Ribosomal Protein L23

Overview

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">RPL23 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>RPL23</td></tr>
<tr><td><strong>Full Name</strong></td><td>Ribosomal Protein L23</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>17q21.31</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9349](https://www.ncbi.nlm.nih.gov/gene/9349)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[604563](https://www.omim.org/entry/604563)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000125691</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P62829](https://www.uniprot.org/uniprot/P62829)</td></tr>
<tr><td><strong>Protein Size</strong></td><td>140 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Diamond-Blackfan Anemia, Alzheimer's Disease, Parkinson's Disease, Ribosomopathies</td></tr>
</table>
</div>

RPL23 Gene — Ribosomal Protein L23

Overview

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">RPL23 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>RPL23</td></tr>
<tr><td><strong>Full Name</strong></td><td>Ribosomal Protein L23</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>17q21.31</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9349](https://www.ncbi.nlm.nih.gov/gene/9349)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[604563](https://www.omim.org/entry/604563)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000125691</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P62829](https://www.uniprot.org/uniprot/P62829)</td></tr>
<tr><td><strong>Protein Size</strong></td><td>140 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Diamond-Blackfan Anemia, Alzheimer's Disease, Parkinson's Disease, Ribosomopathies</td></tr>
</table>
</div>

RPL23 encodes ribosomal protein L23, a component of the 60S large ribosomal subunit. While traditionally known for its role in protein synthesis, RPL23 has gained attention for its extraribosomal functions, particularly in p53 activation following ribosomal stress. In neurons, RPL23 is essential for maintaining protein homeostasis, and its dysfunction has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. Mutations in RPL23 cause Diamond-Blackfan anemia, demonstrating its critical role in hematopoiesis and cellular proliferation [@wilson2019].

Gene Structure and Expression

Genomic Organization

• Chromosomal location: 17q21.31
• Genomic size: ~4.5 kb
• Exon count: 5 exons
• Protein: 140 amino acids, ~14.9 kDa

Gene Family

RPL23 belongs to the ribosomal protein L23 family:

• Paralogs: RPL23A (highly similar, likely from gene duplication)
• Orthologs: Conserved across eukaryotes
• Pseudogenes: RPL23P1 (processed pseudogene)

Tissue Distribution

RPL23 exhibits ubiquitous expression:

• Brain: High expression in cortex, hippocampus, cerebellum
• Bone marrow: High expression in hematopoietic cells
• Liver: Moderate expression
• Kidney: Moderate expression
• Heart: Low-moderate expression

Cellular Localization

RPL23 has dual localization:

Protein Structure and Function

Structural Features

RPL23 contains characteristic ribosomal protein domains:

| Domain | Position | Function |
|--------|----------|----------|
| N-terminal domain | 1-50 aa | rRNA binding, ribosome assembly |
| Central domain | 51-100 aa | Interprotein interactions |
| C-terminal domain | 101-140 aa | MDM2 binding, p53 activation |

Ribosomal Function

Extraribosomal Functions

Beyond translation, RPL23 has important regulatory roles:

• p53 activation: Binds MDM2 under ribosomal stress
• Cell cycle regulation: Modulates G1/S transition
• Apoptosis: Promotes apoptosis when ribosomal integrity compromised
• DNA repair: Involved in DNA damage response

Role in Protein Synthesis

Translation Process

RPL23 contributes to several translation steps:

Neuronal Translation

In neurons, protein synthesis is critical for:

• Synaptic plasticity: Local translation at synapses
• Axonal growth: Protein synthesis in growth cones
• Memory formation: Translation-dependent LTP/LTD
• Neurorepair: Response to injury

Role in Neurodegeneration

Alzheimer's Disease

RPL23 alterations contribute to AD pathogenesis [@kapasi2015]:

Ribosomal dysfunction:

• Global translation reduction in AD brain
• RPL23 levels altered in vulnerable regions
• Correlates with cognitive decline

• Amyloid-β affects ribosomal function
• Tau pathology disrupts translation machinery
• RPL23 may affect amyloid processing

Parkinson's Disease

In PD, RPL23 plays several roles [@andersen2019]:

• Protein homeostasis: Disrupted RPL23 affects proteostasis
• Stress granules: RPL23 in stress granule formation
• Alpha-synuclein: Interaction with aggregation pathways
• Mitochondrial function: Links to PD pathology

Ribosomal Stress Response

RPL23 is central to ribosomal stress signaling [@bhat2019]:

Diamond-Blackfan Anemia

Disease Overview

RPL23 mutations cause DBA, a ribosomopathy characterized by:

• Pure red cell aplasia: Impaired erythropoiesis
• Growth retardation: Developmental delays
• Physical anomalies: Variable congenital features
• Cancer risk: Increased malignancy risk

Molecular Mechanism

| Defect | Consequence |
|--------|-------------|
| Haploinsufficiency | Reduced RPL23 protein |
| Ribosome biogenesis defect | Impaired 60S assembly |
| p53 activation | Cell cycle arrest |
| Erythroid precursor death | Anemia |

Treatment Implications

• Corticosteroids: First-line treatment
• Lenalidomide: Effective in some patients
• Gene therapy: Potential future approach

Therapeutic Implications

Target Strategies

| Approach | Mechanism | Status |
|----------|-----------|--------|
| Ribosome modulators | Enhance translation | Research |
| p53 pathway modulators | Fine-tune stress response | Preclinical |
| Protein homeostasis enhancers | Restore proteostasis | Discovery |
| Small molecule stabilizers | Stabilize ribosomal function | Research |

Potential Applications

• Alzheimer's disease: Enhance neuronal protein synthesis
• Parkinson's disease: Modulate stress granule dynamics
• Ribosomopathies: Correct ribosomal function
• Aging: Maintain protein homeostasis

Expression in Disease States

Altered Patterns

• AD brain: Reduced RPL23 expression
• PD brain: Altered RPL23 levels in substantia nigra
• Aging: Gradual decline in ribosomal function
• Cancer: Often upregulated (pro-proliferative)

Protein Aggregates

RPL23 interactions with pathological proteins:

• Tau: Found in some tau aggregate preparations
• TDP-43: Detected in some ALS inclusions
• Alpha-synuclein: May interact in PD

Animal Models

• RPL23 knockout mice: Embryonic lethal
• Heterozygous mice: Phenotypes similar to DBA
• Knock-in models: Specific human mutations
• Zebrafish: Developmental studies

Cross-Links

• [Ribosome](/proteins/ribosome)
• [p53 Pathway](/mechanisms/p53-signaling)
• [Protein Synthesis](/mechanisms/protein-synthesis)
• [Ribosomal Stress](/mechanisms/ribosomal-stress-response)
• [Stress Granules](/mechanisms/stress-granules)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

See Also

• [Genes Index](/genes)
• [Proteins Index](/proteins)
• [Mechanisms Index](/mechanisms)
• [Ribosomal Proteins](/proteins/ribosomal-proteins)

External Links

• [NCBI Gene: RPL23](https://www.ncbi.nlm.nih.gov/gene/9349)
• [UniProt: P62829](https://www.uniprot.org/uniprot/P62829)
• [Ensembl: ENSG00000125691](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000125691)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving RPL23 Gene discovered through SciDEX knowledge graph analysis: