TRMU

tRNA mitochondrial 2-thiouridylase

Basic information

Region (hg38): 22:46330875-46357340

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 (Definitive), 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 (609 variants)
Acute_infantile_liver_failure_due_to_synthesis_defect_of_mtDNA-encoded_proteins (158 variants)
Aminoglycoside-induced_deafness (90 variants)
Inborn_genetic_diseases (63 variants)
not_specified (46 variants)
TRMU-related_disorder (45 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
Long_QT_syndrome (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. These statistics are base on transcript: NM_000018006.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	215 clinvar	5 clinvar	228
missense	4 clinvar	18 clinvar	140 clinvar	16 clinvar	5 clinvar	183
nonsense	13 clinvar	14 clinvar				27
start loss	1	2				3
frameshift	32 clinvar	48 clinvar				80
splice donor/acceptor (+/-2bp)	2 clinvar	35 clinvar	2 clinvar			39
Total	52	117	150	231	10

Highest pathogenic variant AF is 0.00020631842

Loading clinvar variants...

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