RPS15 Gene

HGNC Family	S ribosomal proteins (RPS)
Name	ribosomal protein S15
Description	Ribosomes, the organelles 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 40S subunit. The protein belongs to the S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRibosomal protein S15 (RPS15), a conserved component of the 40S ribosomal subunit, can exert extraribosomal functions by directly interacting with MDM2. This binding inhibits MDM2’s E3 ubiquitin ligase activity, leading to stabilization of the tumor suppressor p53 and subsequent cell cycle arrest—revealing a quality‐control pathway that links ribosome biogenesis to the regulation of cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in ribosome function, RPS15 is implicated in neurodegeneration. In models of Parkinson’s disease, pathogenic LRRK2 phosphorylates RPS15, which stimulates both cap‐dependent and cap‐independent mRNA translation. This aberrant upregulation of protein synthesis contributes to dopamine neuron degeneration and locomotor deficits, thus providing a mechanistic link between elevated LRRK2 kinase activity and neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in RPS15 have emerged as early genetic lesions in chronic lymphocytic leukemia (CLL). Recurrent somatic missense alterations within a highly conserved seven–amino acid region of RPS15 impair proper p53 regulation by enhancing ubiquitin‐mediated degradation. Moreover, these mutations rewire the translational program, diminishing both efficiency and fidelity, and are associated with an aggressive clinical course in CLL."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies further reveal that the conserved C-terminal tail of RPS15 (also known as uS19) is critical for accurate mRNA decoding and translation elongation. Structural and functional analyses indicate that this tail facilitates the accommodation of aminoacyl-tRNA at the ribosomal A site and is essential for both early pre-40S ribosomal particle maturation and later elongation steps during translation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional oncogenic roles of RPS15 have been observed in solid tumors; for example, its overexpression in esophageal squamous cell carcinoma enhances cell proliferation and metastasis by promoting the translation of key p38 MAPK pathway proteins. Moreover, systems-level analyses have identified RPS15 as a core gene associated with ischemic stroke, underscoring its broader impact on cellular homeostasis and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lilyn Daftuar, Yan Zhu, Xavier Jacq, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal proteins RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0068667"}], "href": "https://doi.org/10.1371/journal.pone.0068667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23874713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23874713"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ian Martin, Jungwoo Wren Kim, Byoung Dae Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.01.064"}], "href": "https://doi.org/10.1016/j.cell.2014.01.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24725412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24725412"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Viktor Ljungström, Diego Cortese, Emma Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2015-10-674572"}], "href": "https://doi.org/10.1182/blood-2015-10-674572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26675346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26675346"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gabriel Bretones, Miguel G Álvarez, Javier R Arango, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2017-09-804401"}], "href": "https://doi.org/10.1182/blood-2017-09-804401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30181176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30181176"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Stavroula Ntoufa, Marina Gerousi, Stamatia Laidou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RPS15 mutations rewire RNA translation in chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Adv (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/bloodadvances.2020001717"}], "href": "https://doi.org/10.1182/bloodadvances.2020001717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34251413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34251413"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elena S Babaylova, Alexander V Gopanenko, Konstantin N Bulygin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mRNA regions where 80S ribosomes pause during translation elongation in vivo interact with protein uS19, a component of the decoding site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz1145"}], "href": "https://doi.org/10.1093/nar/gkz1145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31802126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31802126"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Konstantin Bulygin, Alexey Malygin, Alexander Gopanenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The functional role of the C-terminal tail of the human ribosomal protein uS19."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gene Regul Mech (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2020.194490"}], "href": "https://doi.org/10.1016/j.bbagrm.2020.194490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31991215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31991215"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ingrid Rössler, Sarah Weigl, José Fernández-Fernández, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2022.2064073"}], "href": "https://doi.org/10.1080/15476286.2022.2064073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35438042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35438042"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yahui Zhao, Yang Li, Rui Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RPS15 interacted with IGF2BP1 to promote esophageal squamous cell carcinoma development via recognizing m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A modification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-023-01428-1"}], "href": "https://doi.org/10.1038/s41392-023-01428-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37264021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37264021"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Man Zhao, Aixian Liu, Linhong Mo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The value of RPS15 and MRPS27 in ischemic stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000034706"}], "href": "https://doi.org/10.1097/MD.0000000000034706"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37603533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37603533"}]}]}]}
Synonyms	S15, RIG
Proteins	RS15_HUMAN
NCBI Gene ID	6209
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RPS15 has 15,505 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 115 datasets.

Click the + buttons to view associations for RPS15 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RPS15 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by RPS15 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS15 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS15 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of RPS15 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of RPS15 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of RPS15 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPS15 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of RPS15 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RPS15 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of RPS15 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of RPS15 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RPS15 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RPS15 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RPS15 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RPS15 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RPS15 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of RPS15 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RPS15 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RPS15 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RPS15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RPS15 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RPS15 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RPS15 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with RPS15 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing RPS15 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RPS15 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RPS15 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RPS15 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RPS15 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DGIdb Drug Targets 2026	interacting drugs for RPS15 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RPS15 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RPS15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with RPS15 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with RPS15 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RPS15 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RPS15 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RPS15 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RPS15 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing RPS15 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RPS15 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.