CTU2

Chr 16AR

cytosolic thiouridylase subunit 2

Also known as: C16orf84, MFRG, NCS2, UPF0432

NCBI Gene: 348180 ENSG00000174177 UniProt: Q2VPK5 OMIM: 617057

This protein performs 2-thiolation of specific uridine residues at wobble positions in tRNAs, which enhances codon reading accuracy during protein synthesis. Biallelic mutations cause microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome with autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants, which is consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.501 OMIM phenotype

Clinical Summary— CTU2

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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

12 unique Pathogenic / Likely Pathogenic· 212 VUS of 411 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-3.95Z-score

OE missense 1.62 (1.51–1.75)

514 obs / 316.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.83–1.50)

0≤0.351.4

Missense OE?1.62 (1.51–1.75)

0≤0.61.4

Synonymous OE?1.79

0≤1.21.6

LoF obs/exp: 31 / 28.0Missense obs/exp: 514 / 316.4Syn Z: -7.23

ClinVar Variant Classifications

411 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic4

VUS212

Likely Benign99

Benign51

Conflicting12

Pathogenic

Likely Pathogenic

212

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	5	1	8
Likely Pathogenic	4	0	0	0	4
VUS	2	193	15	2	212
Likely Benign	2	11	47	39	99
Benign	3	16	19	13	51
Conflicting	—				12
Total	13	220	86	55	386

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

View in ClinVar →

66 pathogenic / likely-pathogenic (of 92) ClinVar copy-number / structural variants overlap CTU2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →