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Queuosine-tRNA alpha-mannosyltransferase (QTMAN)
- Target
- QTMAN
- Molecular classification
- Enzyme, Glycosyltransferase (specifically, GT4 family—GT-B fold glycosyltransferase)
01
Overview
Queuosine-tRNA alpha-mannosyltransferase (QTMAN), also known as GTDC1, is a glycosyltransferase enzyme that catalyzes the addition of a mannose residue to queuosine-modified tRNA, specifically on tRNA-Asp. This modification, termed mannosyl-queuosine (manQ), plays a regulatory role in translation by fine-tuning codon decoding speed and maintaining proteostasis through its influence on protein folding. QTMAN is a member of the GT4 glycosyltransferase family (GT-B fold) and uses GDP-mannose as its sugar donor. Disruption of QTMAN affects translation efficacy, leads to protein aggregation, and is linked to both cancer biology (with prognostic implications across tumor types) and neurodevelopmental disorders (via altered glycine metabolism and NMDA receptor signaling). The enzyme is highly conserved and essential for normal organismal development and neurological function, with recent research highlighting its central role in RNA glycosylation and the emerging field of epitranscriptomics.
- Other names
- GTDC1Glycosyltransferase-like domain-containing protein 1Mannosyltransferase-like protein XaMat-XaHmat-XatRNA-queuosine alpha-mannosyltransferasemannosyltransferase-like protein Xamannosyltransferase-likemat-XaFLJ11753
02
Biological functions
Transfer of mannose to queuosine-modified tRNA (specifically to tRNA-Asp)Modulation of tRNA function and codon-anticodon interaction during translationRegulation of protein synthesis and translation speed for specific codonsMaintenance of proteostasis through influence on protein folding
03
Disease associations
Cancer (expression levels associated with prognosis in certain tumor types; QTMAN expression correlates with differing outcomes in liver vs. brain cancers)Neurodevelopmental disorders (de novo deletions or mutations linked to encephalopathy, epilepsy, microcephaly, and developmental delay, due to altered glycine metabolism and NMDA receptor activity)
04
Safety considerations
Potential therapeutic challenges involved in targeting a fundamental tRNA modification enzyme, as loss-of-function may impair translation fidelity and proteostasis, leading to protein misfolding and neurodevelopmental issuesGenetic disruption is associated with neurodevelopmental impairment and epilepsy
05
Biomarkers
Expression of QTMAN (GTDC1) may serve as a biomarker for prognosis in brain and liver tumorsLoss or mutation associated with neurodevelopmental phenotypes
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