CTU2

protein-coding

cytosolic thiouridylase subunit 2

Gene summary

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]

Previous symbols:

C16orf84

MANE transcript

NM_001012759.3

Inheritance

ClinVar variants

P:13U:212B:87

Top phenotype

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

gnomAD constraint

pLI —, LoF o/e 1.11

Max pathogenic AF

—

Genomic locus

chr16:88,706,483-88,715,396

External References & Databases

Ensembl (ENSG00000174177)

Transcript & Mutation Effects

hg38 • Region Span ~8.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020647

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020647

Submitter: Ambry Genetics

microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020647

Submitter: G2P

Clinical Genomic Database (CGD)

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

Manifestation: Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26633546; 27480277

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTU2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 199

not providedTotal: 185

CTU2-related disorderTotal: 53

Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndromeTotal: 22

Congenital anomaly of kidney and urinary tractTotal: 2

See casesTotal: 2

Differences in sex developmentTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012759.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		2 clinvar	51 clinvar	7 clinvar	61
missense		2 clinvar	202 clinvar	18 clinvar	9 clinvar	231
nonsense		2 clinvar	3 clinvar			5
start loss						0
frameshift	2 clinvar	2 clinvar		1 clinvar		5
splice donor/acceptor (+/-2bp)		4 clinvar	5 clinvar		1 clinvar	10
Total	3	10	212	70	17	312

Highest pathogenic variant AF is 0.0010508368

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012759.3	RefSeq	NP_001012777.1	15	MANE Select
ENST00000453996.7	Ensembl	ENSP00000388320.2	15	MANE Select
NM_001012762.3	RefSeq	NP_001012780.1	14	Standard
NM_001318507.2	RefSeq	NP_001305436.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sulfur relay system - Homo sapiens (human)
tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA wobble uridine modification
tRNA wobble position uridine thiolation
protein urmylation
tRNA thio-modification

Molecular Function

tRNA binding
protein binding
nucleotidyltransferase activity
sulfurtransferase activity

Cellular Component

cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000453996
Coding exons: 15
Length: 8924
Individuals with no LoFs: 2997
Homozygous LoFs: 78910
Heterozygous LoFs: 43805
Defined: 125712
p: 0.846

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.95	514	316	1.62	0.0000198	3276
Missense (PolyPhen)		133	82.967	1.603		801
Synonymous	-7.23	243	136	1.79	0.00000917	1051
Loss of Function	-0.533	31	28.0	1.11	0.00000141	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0.87	0.80	notable
Latino/Admixed American	0.87	0.86	notable
Ashkenazi Jewish	0.98	0.89	notable
East Asian	0.92	0.91	notable
Finnish	0.90	0.81	notable
European (Non-Finnish)	0.94	0.84	notable
South Asian	0.87	0.86	notable
Other	0.93	0.87	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). May act by forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position. {ECO:0000255|HAMAP-Rule:MF_03054, ECO:0000269|PubMed:19017811}.;

Intolerance Scores

LoFtool: 0.989
RVIS EVS: 1.43
RVIS percentile EVS: 95.02

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High