Affinage

RPL13

Large ribosomal subunit protein eL13 · UniProt P26373

Length
211 aa
Mass
24.3 kDa
Annotated
2026-06-10
15 papers in source corpus 5 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL13 (eL13) is an integral structural component of the 60S large ribosomal subunit that is required for proper ribosome assembly and global translation (PMID:32916022, PMID:7557437). Disease-causing mutations do not destabilize the protein or its incorporation into 60S subunits, but reduce its colocalization with the partner protein eL28, elevate the ratio of 60S subunits to mature 80S ribosomes, and attenuate global translation, indicating a defect in subunit joining or ribosome maturation rather than in protein expression (PMID:32916022). Splice variants that introduce an 18-amino-acid insertion are likewise stably expressed and incorporated into 60S subunits yet alter ribosome profiles and erythroid proliferation, consistent with changed translation dynamics (PMID:31630789). Beyond its core ribosomal role, RPL13 is highly expressed in chondrocytes and osteoblasts of the growth plate and is required for skeletogenesis in vivo, as rpl13-mutant zebrafish develop cartilage deformities (PMID:31630789, PMID:32916022); it is also required for cardiogenesis, with knockdown impairing cardiomyocyte proliferation and differentiation in human iPSC-derived progenitors and producing a 'no heart' phenotype in Drosophila (PMID:31625562). These tissue-specific requirements underlie the skeletal dysplasia SEMD-RPL13, in which causative variants cluster within an RNA-binding motif (PMID:32916022, PMID:37993442). Whether RPL13 carries out extra-ribosomal mRNA-binding functions has not been experimentally established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 1995 Medium

    Established the molecular identity of the gene, defining BBC1 as the ribosomal protein L13 conserved from fly to mammal and placing it within the translation machinery.

    Evidence cDNA cloning and sequence alignment against rat ribosomal protein L13, with developmental Northern blot analysis in Drosophila

    PMID:7557437

    Open questions at the time
    • Sequence identity alone does not demonstrate position or function within the assembled ribosome
    • No structural or biochemical characterization of the protein in this work
  2. 2019 Medium

    Linked RPL13 to human disease and showed that splice variants act not by loss of protein but by altering ribosome behavior, reframing the pathology as a translation-dynamics defect.

    Evidence Splicing/RT-PCR analysis, sucrose gradient ribosome profiling and erythroid proliferation assays in patient-derived cells; concurrent localization of eL13 in mouse growth plate chondrocytes and osteoblasts

    PMID:31630789

    Open questions at the time
    • Mechanism by which the 18-aa insertion alters translation dynamics not resolved
    • Tissue-specificity of skeletal phenotype not mechanistically explained by ubiquitous ribosomal protein
  3. 2019 Medium

    Demonstrated a conserved developmental requirement for RPL13 in heart formation, extending its role beyond housekeeping translation to organ-specific morphogenesis.

    Evidence siRNA knockdown in human iPSC-derived cardiac progenitors and heart-specific RNAi in Drosophila with cardiac phenotype quantification

    PMID:31625562

    Open questions at the time
    • Whether the cardiac phenotype reflects a translation defect or an extra-ribosomal role not distinguished
    • No identification of specific transcripts whose translation depends on RPL13
  4. 2020 Medium

    Defined the cellular mechanism of missense pathogenicity as impaired ribosome assembly, showing variants reduce eL13/eL28 colocalization and shift the 60S:80S balance while preserving protein stability.

    Evidence Co-localization immunofluorescence (eL13/eL28), sucrose gradient ribosome profiling and global translation assays in patient fibroblasts; CRISPR-Cas9 rpl13 knockout zebrafish with skeletal phenotyping

    PMID:32916022

    Open questions at the time
    • Whether reduced eL28 colocalization is cause or consequence of the assembly defect unresolved
    • Step in 60S maturation/subunit joining that is blocked not pinpointed
  5. 2023 Low

    Mapped disease variants onto an RNA-binding motif, raising the hypothesis that disrupted mRNA interactions contribute to the skeletal phenotype.

    Evidence Structural modeling and mutational clustering analysis of variant positions relative to an RNA-binding motif

    PMID:37993442

    Open questions at the time
    • Computational prediction only; extra-ribosomal mRNA binding not experimentally demonstrated
    • No identified mRNA targets
    • Does not separate ribosomal from putative extra-ribosomal contributions to disease

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether RPL13 has bona fide extra-ribosomal mRNA-binding functions and which specific transcripts or assembly steps drive its tissue-selective requirements in skeleton and heart.
  • No direct biochemical demonstration of mRNA binding
  • No mechanistic explanation for tissue specificity of a ubiquitous ribosomal protein
  • Precise ribosome assembly step affected not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005840 ribosome 3
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-392499 Metabolism of proteins 2
Partners
RPL27A
Complex memberships
60S ribosomal subunit

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 RPL13 splice variants (c.477+1G>T, c.477+1G>A, c.477+2T>C) cause partial intron retention resulting in an 18-amino acid insertion; the insertion-containing protein is stably expressed and incorporated into 60S ribosomal subunits similarly to wild-type RPL13, yet erythroid proliferation and ribosome profiles on sucrose gradients are altered, suggesting a change in translation dynamics rather than pre-rRNA processing defects. Sucrose gradient ribosome profiling, erythroid proliferation assay, RT-PCR/splicing analysis, patient-derived cell lines American journal of human genetics Medium 31630789
2019 RPL13 (eL13) is a component of the 60S ribosomal subunit; RPL13 is expressed at high levels in chondrocytes and osteoblasts in mouse growth plates, establishing its presence in bone-forming cells. Immunohistochemistry/immunostaining of mouse growth plate tissue; ribosome incorporation shown by sucrose gradient sedimentation American journal of human genetics Medium 31630789
2020 RPL13 missense mutations in patient-derived fibroblasts result in normal eL13 expression and proper subcellular localization, but reduced colocalization with eL28, a significant increase in the ratio of 60S subunits to 80S ribosomes, and attenuated global translation, indicating impaired ribosome assembly/function without loss of protein stability. Co-localization immunofluorescence (eL13/eL28), sucrose gradient ribosome profiling, global translation assay in patient-derived dermal fibroblasts Journal of bone and mineral research Medium 32916022
2020 CRISPR-Cas9-generated rpl13 mutant zebrafish display cartilage deformities at embryonic and juvenile stages, establishing that rpl13 is required for skeletogenesis in vivo. CRISPR-Cas9 zebrafish knockout, skeletal phenotype analysis Journal of bone and mineral research Medium 32916022
2019 Knockdown of RPL13 in human iPSC-derived multipotent cardiac progenitor cells reduced proliferation and differentiation of cardiomyocytes while increasing fibroblast numbers; heart-specific RpL13 knockdown in Drosophila predominantly at embryonic stages caused a 'no heart' phenotype, demonstrating a conserved requirement for RPL13 in cardiogenesis. siRNA knockdown in human iPSC-derived cardiac progenitor cells, in vivo Drosophila heart-specific RNAi knockdown with cardiac phenotype quantification Human molecular genetics Medium 31625562
2023 Structural analysis of RPL13 variants reveals that disease-causing mutations cluster in a highly specific RNA-binding motif; interpretation of variant impacts on protein structure suggests that disruption of extra-ribosomal functions through mRNA binding may contribute to the skeletal phenotype of SEMD-RPL13. Structural modeling/in silico analysis of variant positions relative to RNA-binding motif; mutational clustering analysis NPJ genomic medicine Low 37993442
1995 The Drosophila BBC1 protein (RPL13 ortholog) shares 74% sequence similarity with the human BBC1/RPL13 protein and high identity with rat ribosomal protein L13, establishing BBC1 as the ribosomal protein L13. cDNA cloning, sequence alignment, developmental expression analysis by Northern blot Gene Medium 7557437

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature. American journal of human genetics 27 31630789
2019 Model system identification of novel congenital heart disease gene candidates: focus on RPL13. Human molecular genetics 24 31625562
1993 Two related, low-temperature-induced genes from Brassica napus are homologous to the human tumour bbc1 (breast basic conserved) gene. Plant molecular biology 22 8292785
1995 The Drosophila melanogaster homologue of the human BBC1 gene is highly expressed during embryogenesis. Gene 19 7557437
2020 Novel RPL13 Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 32916022
1997 Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes. British journal of cancer 16 9413939
2019 The S. pombe adaptor protein Bbc1 regulates localization of Wsp1 and Vrp1 during endocytic actin patch assembly. Journal of cell science 13 31391237
2001 Enhanced tolerance against salt-stress and freezing-stress of Escherichia coli cells expressing algal bbc1 gene. Current microbiology 13 11270650
1995 Mapping of the breast basic conserved gene (D16S444E) to human chromosome band 16q24.3. Cytogenetics and cell genetics 13 7956357
2023 Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13. NPJ genomic medicine 4 37993442
2023 Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13-related: Description of 11 further cases. Clinical genetics 3 37121912
2024 Bombyx mori RPL13 participates in UV-induced DNA damage repair of B. mori nucleopolyhedrovirus through interaction with Bm65. Insect molecular biology 2 38801334
2025 Beyond the Known: Expanding the Clinical and Genetic Spectrum of Rare RPL13-Related Spondyloepimetaphyseal Dysplasia. International journal of molecular sciences 1 40725227
2024 [Clinical and genetic analysis of a patient with short stature due to variant of RPL13 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 38684306
2023 [Syndromic growth retardation caused by impaired function of the ribosomal protein eL13]. Problemy endokrinologii 0 39069777

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