THG1L: tRNA-Histidine Guanylyltransferase 1 Like
A mitochondrial tRNA modification enzyme implicated in mitochondrial translation and disease
Gene Information Card
| Symbol | THG1L |
|---|---|
| Full Name | tRNA-histidine guanylyltransferase 1 like |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.3 |
| NCBI Gene ID | 54974 ncbi.nlm.nih.gov/gene/54974 |
| Ensembl ID | ENSG00000113558 |
| UniProt ID | Q9NWU5 |
| OMIM ID | 617044 |
| HGNC ID | 20696 |
| Aliases | THG1, ICF45, CGI-55 |
Description
THG1L encodes a mitochondrial protein that catalyzes the 3'-5' addition of a guanine nucleotide to the 5' end of tRNA-His, a unique post-transcriptional modification essential for mitochondrial translation. The enzyme is localized to the mitochondrion and is required for proper mitochondrial function. Mutations in THG1L have been linked to mitochondrial respiratory chain deficiencies and early-onset neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 35 | Loss-of-function mutations impair tRNA-His maturation, reducing mitochondrial translation and complex I assembly | ClinVar, OMIM |
| Leigh syndrome | Severe biallelic THG1L variants disrupt mitochondrial protein synthesis, leading to neurodegeneration | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal Muscle | 9.8 | Medium |
| Liver | 6.5 | Low |
| Brain | 5.2 | Low |
| Kidney | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression |
| HeLa | 11.2 | Moderate expression |
| HepG2 | 8.7 | Moderate expression |
| K562 | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/Start loss | Rare | Loss of translation initiation, reduced protein levels |
| c.226C>T (p.Arg76Trp) | Missense | <0.01% | Impaired catalytic activity, mitochondrial dysfunction |
| c.404G>A (p.Arg135Gln) | Missense | <0.01% | Decreased tRNA guanylyltransferase activity |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense and start-loss variants reduce or abolish enzymatic activity, leading to mitochondrial translation defects.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • tRNA guanylyltransferase activity | • mitochondrion |
| • tRNA processing | • mitochondrial translation |
| • nucleotide binding |
Pathways
• Mitochondrial tRNA modification
• Mitochondrial translation elongation
Protein Summary
THG1L is a 359-amino acid mitochondrial protein that belongs to the tRNA-histidine guanylyltransferase family. It catalyzes the unique 3'-5' addition of GMP to the 5' end of tRNA-His, a critical step for tRNA stability and function in mitochondrial translation. The protein contains a conserved catalytic domain and is essential for mitochondrial respiratory chain complex assembly.
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