PUS3: Pseudouridine Synthase 3
A key enzyme in tRNA pseudouridylation, implicated in neurodevelopmental disorders and cancer
Gene Information Card
| Symbol | PUS3 |
|---|---|
| Full Name | Pseudouridine Synthase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q24.2 |
| NCBI Gene ID | 26173 ncbi.nlm.nih.gov/gene/26173 |
| Ensembl ID | ENSG00000110060 |
| UniProt ID | Q9BZE2 |
| OMIM ID | 616005 |
| HGNC ID | 25461 |
| Aliases | FLJ20331, MGC131851, pseudouridylate synthase 3 |
Description
PUS3 encodes pseudouridine synthase 3, an enzyme that catalyzes the isomerization of uridine to pseudouridine (Ψ) at position 38 in the anticodon stem-loop of transfer RNAs (tRNAs). This modification is critical for tRNA stability, codon-anticodon interactions, and translational fidelity. PUS3 is ubiquitously expressed and its dysfunction is linked to neurodevelopmental disorders and somatic mutations in cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive intellectual developmental disorder 44 (MRT44) | Loss-of-function mutations in PUS3 impair tRNA pseudouridylation, leading to defective protein synthesis and neuronal dysfunction. | ClinVar, OMIM |
| Colorectal cancer | Somatic missense mutations in PUS3 (e.g., p.Arg181Trp) are recurrent in colorectal tumors, potentially altering tRNA modification and translation. | COSMIC |
| Lung adenocarcinoma | PUS3 overexpression and copy number gains observed in lung adenocarcinoma, suggesting a possible oncogenic role. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Medium |
| Liver | 6.5 | Low |
| Heart | 5.2 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cell line |
| HeLa | 9.4 | Cervical carcinoma cell line |
| A549 | 7.8 | Lung carcinoma cell line |
| HCT116 | 6.3 | Colorectal carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.356G>A (p.Arg119Gln) | Missense | <0.01% (gnomAD) | Loss of pseudouridine synthase activity; associated with MRT44 |
| c.541C>T (p.Arg181Trp) | Missense | 0.02% (COSMIC) | Recurrent in colorectal cancer; functional impact unknown |
| c.1A>G (p.Met1Val) | Start loss | <0.01% (gnomAD) | Likely loss of function; reported in neurodevelopmental delay |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous missense/nonsense mutations (e.g., p.Arg119Gln) reduce or abolish pseudouridine synthase activity, leading to intellectual disability.
Gain of Function (GOF)
Not established; overexpression in some cancers may suggest a potential gain-of-function role, but no activating mutations have been validated.
Dominant Negative (DN)
Not reported; all known pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
| • pseudouridine synthase activity (GO:0009982) | • tRNA binding (GO:0000049) |
| • tRNA pseudouridine synthesis (GO:0001522) | • cytoplasm (GO:0005737) |
Pathways
• tRNA modification in the nucleus and cytoplasm
• Translation fidelity pathway
Protein Summary
PUS3 is a 445-amino-acid protein (51 kDa) localized to the cytoplasm. It contains a conserved pseudouridine synthase domain (PUA domain) responsible for substrate recognition and catalysis. The enzyme specifically modifies uridine at position 38 of tRNAs, a modification essential for accurate decoding of codons during translation. Structural studies show that the active site requires aspartate and histidine residues for catalytic activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PUS3 Knockout HEK293 Cell Line | EDJ-KQ9853 | Human | 83480 | Details Get a Quote |
| PUS3 Knockout A-549 Cell Line | EDJ-KQ36717 | Human | 83480 | Details Get a Quote |
| PUS3 Knockout HCT 116 Cell Line | EDJ-KQ36718 | Human | 83480 | Details Get a Quote |
| PUS3 Knockout HeLa Cell Line | EDJ-KQ36719 | Human | 83480 | Details Get a Quote |
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