QTRT2

Chr 3

queuine tRNA-ribosyltransferase accessory subunit 2

Also known as: QTRTD1

NCBI Gene: 79691 ENSG00000151576 UniProt: Q9H974

The protein functions as the non-catalytic subunit of tRNA-guanine transglycosylase, which modifies specific tRNAs by replacing guanine with queuosine at the wobble position of anticodons. Mutations cause autosomal recessive intellectual disability with progressive microcephaly, seizures, and cerebral atrophy. This gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a subunit of tRNA-guanine transglycosylase. tRNA-guanine transglycosylase is a heterodimeric enzyme complex that plays a critical role in tRNA modification by synthesizing the 7-deazaguanosine queuosine, which is found in tRNAs that code for asparagine, aspartic acid, histidine, and tyrosine. The encoded protein may play a role in the queuosine 5'-monophosphate salvage pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.17

Clinical Summary— QTRT2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 VUS of 21 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 0.96

OE 0.78 (0.53–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.63Z-score

OE missense 0.88 (0.79–0.99)

205 obs / 231.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.53–1.17)

0≤0.351.4

Missense OE?0.88 (0.79–0.99)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 17 / 21.8Missense obs/exp: 205 / 231.9Syn Z: -0.01

This gene — mechanism propensity

0.7034th %ile

GOF

0.3986th %ile

LOF

0.2968th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS4

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	4	4
Likely Benign	1	1
Benign	0	0
Total	5	5

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

31 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap QTRT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →