TRMU

tRNA mitochondrial 2-thiouridylase

Basic information

Region (hg38): 22:46330874-46357340

Previous symbols: [ "TRMT" ]

Links

ENSG00000100416 ∙ NCBI:55687 ∙ OMIM:610230 ∙ HGNC:25481 ∙ Uniprot:O75648 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Supportive), mode of inheritance: AR
• mitochondrial myopathy with reversible cytochrome C oxidase deficiency (Supportive), mode of inheritance: Mitochondrial
• acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Strong), mode of inheritance: AR
• acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, aminoglycoside-induced; Liver failure, infantile, transient; Reversible infantile respiratory chain deficiency	AD/AR	Gastrointestinal; Pharmacogenomic	Individuals with aminoglycoside-induced deafness may be at risk of deafness when treated with certain antibiotics; In Liver failure, infantile, transient, with supportive care, patients surviving the initial acute episode can recover and demonstrate typical development; Genetic diagnosis may be beneficial in order to determine therapy	Biochemical; Gastrointestinal	7689389; 11230176; 12408186; 16152638; 19732863; 21931168; 21931168
The inheritance of aminoglycoside-induced deafness may involve multiple, co-segregating variants

ClinVar

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

• not provided (486 variants)
• Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (118 variants)
• Aminoglycoside-induced deafness (62 variants)
• not specified (50 variants)
• Inborn genetic diseases (29 variants)
• Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins;Aminoglycoside-induced deafness (8 variants)
• TRMU-related condition (7 variants)
• Aminoglycoside-induced deafness;Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (5 variants)
• Deafness, mitochondrial, modifier of (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRMU 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			5	138	4	147
missense	1	9	75	29	6	120
nonsense	9	9		2		20
start loss	1					1
frameshift	25	26				51
inframe indel						0
splice donor/acceptor (+/-2bp)	2	27	1			30
splice region		4	9	35		48
non coding			17	73	40	130
Total	38	71	98	242	50

Highest pathogenic variant AF is 0.0000199

Variants in TRMU

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

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

Position	Type	Phenotype	Significance	ClinVar
22-46335127-C-G			Benign (Jun 26, 2018)
22-46335132-C-A			Likely benign (Oct 05, 2018)
22-46335200-CG-C			Benign (Jun 14, 2018)
22-46335294-T-C			Benign (Jun 29, 2018)
22-46335310-GGGA-G		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Aug 10, 2022)
22-46335453-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335484-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335486-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335575-A-T		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335587-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Benign/Likely benign (Jun 14, 2018)
22-46335604-A-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335614-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335618-C-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • Aminoglycoside-induced deafness;Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jul 17, 2021)
22-46335637-A-G		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Likely benign (Jun 26, 2018)
22-46335648-G-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Benign/Likely benign (Jun 14, 2018)
22-46335652-G-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Uncertain significance (Jun 14, 2016)
22-46335678-T-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Conflicting classifications of pathogenicity (Nov 20, 2018)
22-46335714-A-C		TRMU-related disorder	Likely benign (Apr 29, 2021)
22-46335721-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • not specified	Benign/Likely benign (Feb 19, 2018)
22-46335729-C-G		not specified	Likely benign (Mar 05, 2018)
22-46335730-G-A		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • TRMU-related disorder	Uncertain significance (Dec 20, 2023)
22-46335739-A-C			Likely benign (Apr 06, 2018)
22-46335740-G-A			Likely benign (Apr 06, 2018)
22-46335746-G-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • not specified • TRMU-related disorder	Conflicting classifications of pathogenicity (Apr 26, 2021)
22-46335750-T-C		Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRMU	protein_coding	protein_coding	ENST00000290846	11	26466

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.53e-16	0.00335	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.332	247	233	1.06	0.0000129	2766
Missense in Polyphen		90	97.855	0.91973		1185
Synonymous	-3.15	131	92.5	1.42	0.00000546	802
Loss of Function	-0.439	23	20.8	1.10	9.74e-7	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000841	0.000839
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000272	0.000272
South Asian	0.000653	0.000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2- thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base. {ECO:0000269|PubMed:15509579, ECO:0000269|PubMed:15944150, ECO:0000269|PubMed:16826519}.
• Disease: DISEASE: Liver failure, infantile, transient (LFIT) [MIM:613070]: A transient disorder of hepatic function characterized by elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, increased serum lactate. Patients who survive the initial acute episode can recover, show normal development and have no recurrence. {ECO:0000269|PubMed:19732863}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.234

Intolerance Scores

• loftool: 0.835
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.69

Haploinsufficiency Scores

• pHI: 0.198
• hipred: N
• hipred_score: 0.197
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.230

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trmu
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: tRNA wobble position uridine thiolation
• Cellular component: nucleoplasm;mitochondrion
• Molecular function: tRNA binding;ATP binding;sulfurtransferase activity