GTPBP3 Gene: Mitochondrial tRNA Modification and Disease
Essential for mitochondrial translation and linked to combined oxidative phosphorylation deficiency
Gene Information Card
| Symbol | GTPBP3 |
|---|---|
| Full Name | GTP binding protein 3 (mitochondrial) |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 84705 ncbi.nlm.nih.gov/gene/84705 |
| Ensembl ID | ENSG00000130226 |
| UniProt ID | Q969Y2 |
| OMIM ID | 608536 |
| HGNC ID | 14880 |
| Aliases | GTPBG3, COXPD23, MTGP1 |
Description
The GTPBP3 gene encodes a mitochondrial GTP-binding protein that is essential for the post-transcriptional modification of mitochondrial tRNAs, specifically the 5-taurinomethyl modification of the wobble uridine base. This modification is critical for accurate and efficient mitochondrial translation. Mutations in GTPBP3 cause combined oxidative phosphorylation deficiency type 23 (COXPD23), a severe mitochondrial disorder characterized by hypertrophic cardiomyopathy, encephalopathy, and lactic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined oxidative phosphorylation deficiency 23 (COXPD23) | Loss-of-function mutations impair mitochondrial tRNA modification, leading to defective mitochondrial protein synthesis and respiratory chain dysfunction. | ClinVar, OMIM (OMIM: 616198) |
| Hypertrophic cardiomyopathy (secondary) | Mitochondrial dysfunction due to GTPBP3 mutations causes energy deficiency in cardiac muscle, leading to hypertrophy. | Case reports in PubMed (e.g., PMID: 25058215) |
| Encephalopathy / Leigh-like syndrome | Impaired mitochondrial energy production affects the central nervous system, resulting in neurological symptoms. | ClinVar, OMIM (OMIM: 616198) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.1 | Medium |
| Skeletal Muscle | 8.9 | Low |
| Liver | 7.4 | Low |
| Brain | 6.2 | Low |
| Kidney | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.5 | Hepatocellular carcinoma cell line |
| K562 | 8.2 | Chronic myelogenous leukemia |
| A549 | 7.9 | Lung carcinoma |
| MCF7 | 6.8 | Breast adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.950G>A (p.Arg317His) | Missense | Reported in COXPD23 patients | Impairs GTPase activity and tRNA modification |
| c.475C>T (p.Arg159Trp) | Missense | Reported in COXPD23 patients | Disrupts protein function |
| c.1075C>T (p.Arg359Trp) | Missense | Reported in COXPD23 patients | Affects mitochondrial localization |
| c.137A>G (p.Tyr46Cys) | Missense | Reported in COXPD23 patients | Reduces protein stability |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, reducing GTPase activity or protein stability, leading to defective tRNA modification and mitochondrial translation.
Gain of Function (GOF)
No evidence of gain-of-function mutations in GTPBP3.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • mitochondrial tRNA modification | • mitochondrial translation |
| • tRNA binding | • mitochondrion |
Pathways
• Mitochondrial tRNA modification
• Mitochondrial translation
• Oxidative phosphorylation
Protein Summary
GTPBP3 is a nuclear-encoded mitochondrial protein that localizes to the mitochondrial matrix. It forms a heterodimer with MTO1 to catalyze the 5-taurinomethyl modification of the wobble uridine in mitochondrial tRNAs specific for Leu, Lys, Glu, and Gln. This modification is essential for proper codon-anticodon interactions and translational fidelity. Defects in GTPBP3 lead to impaired mitochondrial protein synthesis, causing respiratory chain deficiencies and clinical manifestations such as cardiomyopathy and encephalopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GTPBP3 Knockout HEK293 Cell Line | EDJ-KQ10174 | Human | 84705 | Details Get a Quote |
| GTPBP3 Knockout HCT 116 Cell Line | EDJ-KQ36049 | Human | 84705 | Details Get a Quote |
| GTPBP3 Knockout A-549 Cell Line | EDJ-KQ37283 | Human | 84705 | Details Get a Quote |
| GTPBP3 Knockout HeLa Cell Line | EDJ-KQ37285 | Human | 84705 | Details Get a Quote |
