CTU2

cytosolic thiouridylase subunit 2

Basic information

Region (hg38): 16:88706482-88715396

Previous symbols: [ "C16orf84" ]

Links

ENSG00000174177 ∙ NCBI:348180 ∙ OMIM:617057 ∙ HGNC:28005 ∙ Uniprot:Q2VPK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (Strong), mode of inheritance: AR
• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (Limited), mode of inheritance: AR
• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome	AR	General	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	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	26633546; 27480277

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTU2 gene.

• not provided (135 variants)
• Inborn genetic diseases (59 variants)
• Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (19 variants)
• not specified (2 variants)
• See cases (2 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTU2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	15	29
missense			85	7	15	107
nonsense	1		2			3
start loss						0
frameshift	2					2
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1	1			2
splice region	2		3	5	5	15
non coding				21	17	38
Total	3	1	90	42	47

Highest pathogenic variant AF is 0.000138

Variants in CTU2

This is a list of pathogenic ClinVar variants found in the CTU2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-88706528-C-G		CTU2-related disorder	Likely benign (Jul 30, 2019)
16-88706540-G-A		not specified	Uncertain significance (Feb 22, 2023)
16-88706552-T-A			Uncertain significance (Jul 19, 2022)
16-88706555-G-A		CTU2-related disorder	Benign (Jan 22, 2024)
16-88706566-G-A			Likely benign (Jul 17, 2023)
16-88706579-C-G		not specified	Uncertain significance (Jan 03, 2022)
16-88706610-C-T			Likely benign (Nov 14, 2022)
16-88706618-C-G			Benign (Jul 06, 2023)
16-88707117-C-T		Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome	Benign/Likely benign (Jan 08, 2024)
16-88707120-C-A		CTU2-related disorder	Benign (Jan 29, 2024)
16-88707137-C-T		not specified	Uncertain significance (Nov 21, 2022)
16-88707141-A-C		CTU2-related disorder	Benign (Dec 09, 2023)
16-88707144-A-G		not specified	Uncertain significance (Jan 23, 2023)
16-88707153-T-C		not specified	Uncertain significance (Nov 01, 2022)
16-88707176-G-C		not specified	Uncertain significance (Jan 26, 2022)
16-88707186-T-A		CTU2-related disorder	Uncertain significance (Oct 18, 2023)
16-88707188-C-G		CTU2-related disorder	Uncertain significance (Oct 18, 2023)
16-88707191-G-A			Uncertain significance (Dec 09, 2022)
16-88707213-G-T			Uncertain significance (Jan 15, 2022)
16-88707228-C-A			Likely benign (Sep 06, 2022)
16-88709981-C-G			Uncertain significance (May 08, 2022)
16-88709982-T-C		Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome • CTU2-related disorder	Conflicting classifications of pathogenicity (Dec 07, 2023)
16-88709992-C-G		not specified	Uncertain significance (Mar 08, 2024)
16-88709993-C-T		not specified	Uncertain significance (Nov 08, 2022)
16-88709994-G-A		not specified	Uncertain significance (Dec 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTU2	protein_coding	protein_coding	ENST00000453996	15	8924

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.97e-22	0.000324	2997	78910	43805	125712	0.846

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.95	514	316	1.62	0.0000198	3276
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	1.74	1.67
Ashkenazi Jewish	0.984	0.892
East Asian	0.919	0.906
Finnish	0.899	0.814
European (Non-Finnish)	0.936	0.843
Middle Eastern	0.919	0.906
South Asian	0.866	0.855
Other	0.926	0.870

dbNSFP

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}.
• Pathway: Sulfur relay system - Homo sapiens (human);tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Intolerance Scores

• loftool: 0.989
• rvis_EVS: 1.43
• rvis_percentile_EVS: 95.02

Haploinsufficiency Scores

• pHI: 0.280
• hipred: N
• hipred_score: 0.197
• ghis: 0.536

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctu2

Gene ontology

• Biological process: tRNA wobble uridine modification;tRNA wobble position uridine thiolation;protein urmylation;tRNA thio-modification
• Cellular component: cytosol;protein-containing complex
• Molecular function: tRNA binding;protein binding;nucleotidyltransferase activity;sulfurtransferase activity