MT-TL1

Summary

MT-TL1 (mitochondrially encoded tRNA-Leu (UUA/G) 1, HGNC:7490) is a mitochondrial tRNA gene on chromosome mitochondria.

Predicted to enable triplet codon-amino acid adaptor activity. Predicted to be involved in translation. Implicated in cardiomyopathy.

Source: NCBI Gene 4567 — RefSeq curated summary.

At a glance

• Gene type: non-coding (Mt_tRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7490
Approved symbol	MT-TL1
Name	mitochondrially encoded tRNA-Leu (UUA/G) 1
Location	mitochondria
Locus type	RNA, transfer
Status	Approved
Aliases	TRNL1
Ensembl gene	ENSG00000209082
Ensembl biotype	Mt_tRNA
OMIM	590050
Entrez	4567
RNAcentral	URS000061A10B — tRNA, 75 nt, 5 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 Mt_tRNA

ENST00000386347

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000386347 — 1 exons

Exon	Start	End
ENSE00002006242	3230	3304

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 211.5517 / max 162659.6367, expressed in 1795 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194844	211.5517	1795

Top tissues by expression

118 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal cortex	UBERON:0001870	99.94	gold quality
right frontal lobe	UBERON:0002810	99.94	gold quality
caudate nucleus	UBERON:0001873	99.93	gold quality
apex of heart	UBERON:0002098	99.93	gold quality
skeletal muscle tissue	UBERON:0001134	99.92	gold quality
putamen	UBERON:0001874	99.92	gold quality
amygdala	UBERON:0001876	99.92	gold quality
Ammon’s horn	UBERON:0001954	99.91	gold quality
prefrontal cortex	UBERON:0000451	99.90	gold quality
nucleus accumbens	UBERON:0001882	99.90	gold quality
substantia nigra	UBERON:0002038	99.90	gold quality
hypothalamus	UBERON:0001898	99.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.88	gold quality
heart left ventricle	UBERON:0002084	99.87	gold quality
anterior cingulate cortex	UBERON:0009835	99.85	gold quality
right adrenal gland cortex	UBERON:0035827	99.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.81	gold quality
gastrocnemius	UBERON:0001388	99.78	gold quality
cerebellar hemisphere	UBERON:0002245	99.77	gold quality
right adrenal gland	UBERON:0001233	99.76	gold quality
duodenum	UBERON:0002114	99.72	gold quality
left adrenal gland	UBERON:0001234	99.70	gold quality
adult mammalian kidney	UBERON:0000082	99.68	gold quality
vermiform appendix	UBERON:0001154	99.68	gold quality
left adrenal gland cortex	UBERON:0035825	99.64	gold quality
adrenal gland	UBERON:0002369	99.63	gold quality
fundus of stomach	UBERON:0001160	99.62	gold quality
metanephros cortex	UBERON:0010533	99.56	gold quality
sural nerve	UBERON:0015488	99.55	gold quality
body of stomach	UBERON:0001161	99.52	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	24.31
E-MTAB-9543	no	75.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, JUN, MAF, MAFB, NCOA2, TBP, TP53, ZNF143

Literature-anchored findings (GeneRIF, showing 32)

• Mutation in the mitochondrial tRNA(Ile) gene, A4267G transition, represents a sporadic germline mutation. (PMID:12207935)
• UUG codon-specific translational defect of the mutant mt tRNAs(Leu(UUR)) is the primary cause of MELAS at the molecular level (PMID:15477592)
• A decrease in steady-state levels of mt-tRNALeu(UUR) carrying the 3302A>G mutation in the MTTL1 gene is caused by inefficient cleavage of the precursor RNA19. (PMID:17130166)
• insulin secretory capacity in individuals carrying the A3243G mutation may be the primary defect contributing to the development of diabetes mellitus (PMID:17198195)
• Point mutation occurred in mtDNA might be involved in pathogenesis of multiple sclerosis. (PMID:17619138)
• Detrimental effects of the m.3243A>G mutation (which causes MELAS syndrome) can be compensated by upregulation of genes coding for oxidative phosphorylation complexes, mitochondrial biogenesis, protein turnover, apoptosis, and muscle regeneration. (PMID:18456717)
• Myoblasts isolated from the MELAS patients show A3243G mutation in tRNALeu(UUR) produces a severe respiratory chain deficiency and this phenotype can be partially suppressed by overexpression of EFTu and EFG2. (PMID:18753147)
• The heteroplasmy level of the mitochondrial tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes. (PMID:19382419)
• This is the first reported case of a double-point mutation in mtDNA, tRNA(Lys) and tRNA(Leu) genes, both of which were heteroplasmic and pathogenic for MERRF/MELAS overlap syndrome. (PMID:20610441)
• a single mutation of the mitochondrial deoxyribonucleic acid (DNA) affects both the glucose metabolism and the inner ear physiology. (PMID:21453644)
• A study concludes that the m.3243A > G mutation causes a wide variety of signs and symptoms, maternally inherited diabetes and deafness being the most prevalent phenotypic expression. (PMID:22403016)
• The clinical presentation of the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)varies broadly in patients with the A3243G mutation. (PMID:22747555)
• m.3242G > A de novo mutation found in 3 patients with hypertrophic cardiomyopathy and renal tubular dysfunction. (PMID:22781753)
• The level of C3256T heteroplasmy of mitochondrial genome in human white blood cells is a biomarker of mitochondrial dysfunction and risk factor for atherosclerosis. (PMID:23056349)
• The results of this study indicated a multisystemic mitochondrial disorder associated with the m.3243A>G mutation in MTTL1. (PMID:23196335)
• Patients with the m.3243A.G mutation have a high incidence of cardiac death and life-threatening adverse events. (PMID:23243073)
• We have defined the phenotypic spectrum associated with the MTTL1 mtDNA mutation in 129 patients (PMID:23355809)
• Mitochondrial retinal dystrophy associated with the m.3243A>G mutation has specific characteristics that can be classified into 4 grades. (PMID:23806424)
• m.3460G>A/MT-ND1 mutation caused only a reduction in mitochondrial complex I(CI) activity, whereas the m.3571insC/MT-ND1 and the m.3243A>G/MT-TL1 mutations induced a severe structural and functional CI alteration. (PMID:24163135)
• A heteroplasmic mutation, m.3291T>C, was found in a patient and her normal mother and sister. This study is the first to describe the pathogenic m.3291T>C mutation in association with the MERRF/MELAS overlap syndrome. (PMID:24338029)
• A family with MTTL1 A3243G mutation is described. Clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. (PMID:24534033)
• The results document alterations in glucose metabolism in individuals with the m.3243A>G mutation that contribute significantly to our understanding of the pathogenesis of mitochondrial diabetes mellitus. (PMID:25086207)
• Described is the clinical, pathological, and molecular features of a child and his asymptomatic mother, carrying the m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) gene, in association with hypertrophic cardiomyopathy. (PMID:25680467)
• mutation of transfer RNA(Leu(UUR)) disrupted the highly conserved base pairing (2T-71A) and resulted a failure in mt-tRNA metabolism. Analysis of the mitochondrial copy number showed that the patients with PCOS and insulin resistance had lower copy number than the health controls, suggesting that mitochondrial dysfunction may be involved in the pathogenesis of insulin resistance (PMID:26335180)
• we present comprehensive clinical and laboratory data for 50 individuals with the m.3243A> G MTTL1 mutation, as well as information focusing specifically on the sequence of symptoms. (PMID:27296531)
• The m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease and it can cause intestinal pseudo-obstruction. (PMID:27453452)
• MT-ND4 and MT-TL1 genetic variation might be associated with male infertility in Chinese patients. (PMID:27973917)
• Data suggest that subjects with point mutation 3243A>G in mtRNA-Leu(UUR) develop MIDD (maternally inherited diabetes and deafness); as compared to patients with T1DM (type 1 diabetes mellitus) or early-onset T2DM (type 2 diabetes mellitus) matched for sex, age, duration of diabetes, such MIDD patients have highest rate of osteoporosis. (PMID:28599824)
• Data suggest that a mutation in tRNA(Leu)(UUR) (3253 T->C) in mitochondrial DNA is associated with maternally inherited hypertension in a Han Chinese family; this mutation alters the conformation, stability, and function of tRNA(Leu); tRNA(Leu) with mutation 3253 T->C exhibits 35% reduction in aminoacylation efficiency as compared to control. (PMID:28679533)
• A missense mutation in TRNL1 associated with familial hematuria in a family with focal segmental glomerulosclerosis. (PMID:29138824)
• Study in transmitochondrial cybrid model of MELAS (100% m.3243A>G mutant mitochondrial DNA) provides cutting-edge information on the involvement of microRNAs (miRNAs) in the cell response to the mitochondrial dysfunction associated with mutation m.3243A>G in mitochondrial tRNA Leu(UUR) gene. Some miRNAs are direct regulators of fetal cardiac genes such which are up-regulated in MELAS cybrids. (PMID:29928977)
• Mitochondrial genome variant m.3250T>C as a possible risk factor for mitochondrial cardiomyopathy. (PMID:33259687)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.