CTU2

Chr 16AR

cytosolic thiouridylase subunit 2

Also known as: C16orf84, MFRG, NCS2, UPF0432

NCBI Gene: 348180ENSG00000174177UniProt: Q2VPK5

This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndromeMIM #618142
AR
500
ClinVar variants
77
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CTU2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 Pathogenic / Likely Pathogenic· 230 VUS of 500 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.50LOEUF
pLI 0.000
Z-score -0.53
OE 1.11 (0.83–1.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-3.95Z-score
OE missense 1.62 (1.51–1.75)
514 obs / 316.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.11 (0.83–1.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.62 (1.51–1.75)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.79
0≤1.21.6
LoF obs/exp: 31 / 28.0Missense obs/exp: 514 / 316.4Syn Z: -7.23

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic11
VUS230
Likely Benign98
Benign53
Conflicting12
66
Pathogenic
11
Likely Pathogenic
230
VUS
98
Likely Benign
53
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
63
1
66
Likely Pathogenic
3
0
8
0
11
VUS
0
191
37
2
230
Likely Benign
1
11
48
38
98
Benign
3
16
20
14
53
Conflicting
—12
Total921817655470

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

View in ClinVar →

Protein Context — Lollipop Plot

CTU2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CTU2-related microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

MIM #618142

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic variants in CTU2 cause DREAM-PL syndrome and impair thiolation of tRNA wobble U34.
Shaheen R et al.·Hum Mutat
2019
The syndrome dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly and lissencephaly (DREAM-PL): Report of two additional patients.
Shaheen R et al.·Am J Med Genet A
2016Review
Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort.
Shaheen R et al.·Genet Med
2016Cohort
Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes.
Abualsaud D et al.·Am J Med Genet A
2021Cohort
Effect of Genetic Polymorphism Including NUP153 and SVEP1 on the Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects.
Xiang Q et al.·Clin Drug Investig
2022
A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features.
Palumbo O et al.·Genes (Basel)
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools