TRNT1 Gene: tRNA Nucleotidyl Transferase 1 - Function, Disease Associations, and Clinical Significance
Comprehensive guide to TRNT1 (CCA-adding enzyme), its role in tRNA maturation, associated disorders (SIFD, retinitis pigmentosa, sideroblastic anemia), and mutation spectrum.
Gene Information Card
| Symbol | TRNT1 |
|---|---|
| Full Name | tRNA nucleotidyl transferase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 3p26.2 |
| NCBI Gene ID | 51095 ncbi.nlm.nih.gov/gene/51095 |
| Ensembl ID | ENSG00000114686 |
| UniProt ID | Q96Q11 |
| OMIM ID | 612907 |
| HGNC ID | 16941 |
| Aliases | CCA1, CCA-adding enzyme, mt CCA-adding enzyme, TRNT1, FLJ12770 |
Description
The TRNT1 gene encodes tRNA nucleotidyl transferase 1, an essential enzyme that adds the conserved CCA sequence to the 3' end of transfer RNAs (tRNAs). This modification is critical for tRNA aminoacylation and ribosomal protein synthesis. TRNT1 functions in both the cytoplasm and mitochondria, and its deficiency leads to impaired mitochondrial translation and multiple systemic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD) | Loss-of-function mutations in TRNT1 impair CCA addition, leading to defective tRNA maturation and mitochondrial dysfunction, causing multi-system disease. | ClinVar, OMIM (612907), PMID: 24651126 |
| Retinitis pigmentosa (RP) | TRNT1 mutations cause progressive retinal degeneration due to mitochondrial dysfunction in photoreceptor cells. | ClinVar, PMID: 28771248 |
| Combined oxidative phosphorylation deficiency (mitochondrial disease) | Impaired mitochondrial tRNA processing leads to respiratory chain defects and energy deficiency. | OMIM, PMID: 24651126 |
| Congenital sideroblastic anemia (CSA) | Mitochondrial iron metabolism disruption due to defective translation of mitochondrial proteins. | ClinVar, PMID: 24651126 |
| Immunodeficiency (B-cell deficiency) | TRNT1 mutations affect B-cell development and function, leading to recurrent infections. | OMIM, PMID: 24651126 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Heart | 8.7 | Medium |
| Brain | 6.3 | Low |
| Skeletal Muscle | 5.1 | Low |
| Testis | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | High expression |
| K562 | 12.1 | Medium |
| A549 | 10.8 | Medium |
| HepG2 | 9.5 | Medium |
| MCF7 | 7.2 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.124A>G (p.Lys42Glu) | Missense | Rare (found in SIFD patients) | Impairs catalytic activity, reduces CCA addition |
| c.446T>C (p.Leu149Pro) | Missense | Rare (found in retinitis pigmentosa) | Disrupts protein folding and enzyme function |
| c.868G>A (p.Gly290Arg) | Missense | Rare (found in SIFD) | Affects substrate binding, reduced activity |
| c.1052C>T (p.Pro351Leu) | Missense | Rare (found in SIFD) | Impairs mitochondrial localization |
| c.1225A>G (p.Thr409Ala) | Missense | Rare (found in SIFD) | Reduced enzyme stability |
| c.1357C>T (p.Arg453Trp) | Missense | Rare (found in SIFD) | Loss of function, severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most TRNT1 mutations are loss-of-function, reducing or abolishing CCA-adding activity, leading to impaired tRNA maturation and mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported for TRNT1.
Dominant Negative (DN)
No dominant-negative effects reported; TRNT1 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • nucleotidyltransferase activity | • tRNA binding |
| • ATP binding | • magnesium ion binding |
| • tRNA nucleotidyltransferase activity | • mitochondrion |
| • cytoplasm | • tRNA processing |
| • tRNA 3'-terminal CCA addition | • mitochondrial tRNA processing |
Pathways
• tRNA processing and modification
• Mitochondrial translation
• Aminoacyl-tRNA biosynthesis
Protein Summary
TRNT1 is a 434-amino acid protein that belongs to the nucleotidyltransferase family. It catalyzes the addition of CCA nucleotides to the 3' end of tRNAs, a critical step for tRNA function. The enzyme is localized in both the cytoplasm and mitochondria, with a mitochondrial targeting sequence. It functions as a homodimer and requires divalent metal ions (e.g., Mg2+) for activity. Defects in TRNT1 lead to impaired protein synthesis, particularly in mitochondria, causing a spectrum of clinical phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRNT1 Knockout HEK293 Cell Line | EDJ-KQ51280 | Human | 51095 | Details Get a Quote |
| TRNT1 Knockout HeLa Cell Line | EDJ-KQ56228 | Human | 51095 | Details Get a Quote |
| TRNT1 Knockout A-549 Cell Line | EDJ-KQ64718 | Human | 51095 | Details Get a Quote |
| TRNT1 Knockout HCT 116 Cell Line | EDJ-KQ73162 | Human | 51095 | Details Get a Quote |
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