PUS3 Gene

Name pseudouridylate synthase 3
Description The protein encoded by this gene catalyzes the formation of tRNA pseudouridine from tRNA uridine at position 39 in the anticodon stem and loop of transfer RNAs. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPUS3 encodes a pseudouridine synthase that is essential for post‐transcriptional modification of tRNA by catalyzing the isomerization of uridine to pseudouridine, particularly at positions 38 and 39. Disruption of this activity, through truncating or missense mutations, has been linked to intellectual disability and a broader spectrum of neurodevelopmental disorders characterized by global developmental delay, epilepsy, hypotonia, and microcephaly. These studies underscore that the brain is especially sensitive to perturbations in tRNA modification processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional assays reveal that while some patient-derived mutations in PUS3 do not completely abolish its ability to bind tRNA or perform the pseudouridylation reaction in vitro, they significantly impair the enzyme’s stability or lead to protein aggregation. As a result, reduced overall PUS3 protein levels and diminished pseudouridine modification in patient cells provide a direct molecular explanation for the observed clinical phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHigh-resolution structural studies using cryo-electron microscopy further delineate the molecular basis of PUS3 function, demonstrating that the enzyme forms a symmetric homodimer to accurately recognize and modify its tRNA substrate at the designated uridine positions. Structure-guided analyses and patient-derived mutations validate the role of specific residues in tRNA binding and catalysis, confirming that the precise tRNA modification activity of PUS3 is central to normal brain development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ranad Shaheen, Lu Han, Eissa Faqeih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-016-1665-7"}], "href": "https://doi.org/10.1007/s00439-016-1665-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27055666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27055666"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miriam Nøstvik, Sarah M Kateta, Bitten Schönewolf-Greulich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and molecular delineation of PUS3-associated neurodevelopmental disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.14051"}], "href": "https://doi.org/10.1111/cge.14051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34415064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34415064"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ting-Yu Lin, Robert Smigiel, Bozena Kuzniewska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Destabilization of mutated human PUS3 protein causes intellectual disability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.24471"}], "href": "https://doi.org/10.1002/humu.24471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36125428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36125428"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ting-Yu Lin, Leon Kleemann, Jakub Jeżowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The molecular basis of tRNA selectivity by human pseudouridine synthase 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2024.06.013"}], "href": "https://doi.org/10.1016/j.molcel.2024.06.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38996458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38996458"}]}]}]}
Synonyms MRT55, 2610020J05RIK, FKSG32
Proteins PUS3_HUMAN
NCBI Gene ID 83480
API
Download Associations
Predicted Functions View PUS3's ARCHS4 Predicted Functions.
Co-expressed Genes View PUS3's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View PUS3's ARCHS4 Predicted Functions.

Functional Associations

PUS3 has 4,502 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 97 datasets.

Click the + buttons to view associations for PUS3 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of PUS3 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 PUS3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of PUS3 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 PUS3 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 PUS3 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 PUS3 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 PUS3 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 PUS3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of PUS3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of PUS3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with PUS3 protein from the CCLE Cell Line Proteomics dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of PUS3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of PUS3 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 PUS3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of PUS3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing PUS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing PUS3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing PUS3 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 PUS3 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 PUS3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of PUS3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with PUS3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with PUS3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with PUS3 gene/protein from the curated CTD Gene-Disease Associations dataset.
DeepCoverMOA Drug Mechanisms of Action small molecule perturbations with high or low expression of PUS3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by PUS3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with PUS3 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 PUS3 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 PUS3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with PUS3 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 PUS3 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 PUS3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of PUS3 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 PUS3 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 PUS3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing PUS3 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of PUS3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving PUS3 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving PUS3 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving PUS3 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing PUS3 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing PUS3 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing PUS3 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by PUS3 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by PUS3 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by PUS3 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of PUS3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of PUS3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of PUS3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of PUS3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HMDB Metabolites of Enzymes interacting metabolites for PUS3 protein from the curated HMDB Metabolites of Enzymes dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of PUS3 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of PUS3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of PUS3 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of PUS3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for PUS3 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of PUS3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Kinase Library Serine Threonine Kinome Atlas kinases that phosphorylate PUS3 protein from the Kinase Library Serine Threonine Atlas dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of PUS3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of PUS3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with PUS3 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of PUS3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of PUS3 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of PUS3 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of PUS3 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain PUS3 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MiRTarBase microRNA Targets microRNAs targeting PUS3 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of PUS3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of PUS3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of PUS3 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing PUS3 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for PUS3 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of PUS3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of PUS3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2024 pathways involving PUS3 protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving PUS3 protein from the Reactome Pathways 2024 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of PUS3 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of PUS3 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of PUS3 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of PUS3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at PUS3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of PUS3 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of PUS3 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of PUS3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of PUS3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of PUS3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of PUS3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of PUS3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of PUS3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of PUS3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with PUS3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with PUS3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.